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The complex three-dimensional (3D) anatomy in facial allotransplantation creates a unique challenge for surgical reconstruction. Evolution of virtual surgical planning (VSP) through computer-aided design and computer-aided manufacturing has advanced reconstructive outcomes for many craniomaxillofacial indications. Surgeons use VSP, 3D models, and surgical guides to analyze and to trial surgical approaches even prior to entering the operating room. This workflow allows the surgeon to plan osteotomies and to anticipate challenges, which improves surgical precision and accuracy, optimizes outcomes, and should reduce operating room time. We present the development, evolution, and utilization of VSP and 3D-printed guides in facial allotransplantation at our institution, from guide conception to first clinical case.

With the rising cost of inflation, adults are considering returning to school. Yet, the family-work balance, cost of living, and prices of education create barriers for most, especially diverse adults in low-socioeconomic areas, English language learners (ELLs), and those labeled with a disability. As education has taken the lead in online spaces, barriers still have been overlooked to provide equitable and accessible educational platforms for adults. As motivation for a promising future drives non-traditional minority adult learners (NMALs) to return to school, education must be convenient, cost-effective, and inclusive. Furthermore, advancing technology and digital tools leave both educators and adult learners at a disadvantage. By incorporating professional development, fair access to technology, and WOW practices into online learning environments, barriers will be eliminated for NMALs allowing for systemic equity in online learning platforms.

Online teaching can be intimidating to faculty, and most educators new to online teaching do not have the knowledge necessary to create and flourish a community of learners who are active, engaged, and collaborative. Students need adequate support to be motivated and take responsibility for their learning in online learning environments and authentic learning experiences and assessment tools are integral to this process. Yet, most novice online course instructors don't understand how to translate these kinds of active learning experiences to online course environments. This chapter will go in depth with effective online instructional techniques to help train faculty to motivate online learners through best practices in online pedagogy. Topics include creating a welcoming course environment, creating and moderating engaging course discussions, creating assignments and giving meaningful feedback, motivating students to achieve, and motivating students to work with integrity and academic honesty.

BackgroundEthiopia has one of the highest maternal mortality ratios in Africa. Few have examined the quality of labour and delivery (L&D) care in the country. This study evaluated the quality of routine L&D care and identified patient-and hospital-level factors associated with the quality of care in a subset of government hospitals.Materials and methodsThis was a facility-based, cross-sectional study using direct non-participant observation carried out in 2016. All mothers who received routine L&D care services at government hospitals (n=20) in one of the populous regions of Ethiopia, Southern Nations Nationalities and People’s Region (SNNPR), were included. Mixed effects multilevel linear regression modeling was employed in two stages using hospital as a random effect, with quality of L&D care as the outcome and selected patient and hospital characteristics as independent variables. Patient characteristics included woman’s age, number of previous births, number of skilled attendants involved in care process, and presence of any danger sign in current pregnancy.Hospital characteristics included teaching hospital status, mean number of attended births in the previous year, number of fulltime skilled attendants in the L&D ward, whether the hospital had offered refresher training on L&D care in the previous 12 months, and the extent of resources available (measured on a 0-100% scale) to provide quality L&D care as defined by the Ethiopian Ministry of Health in 2014. The outcome was measured with a quality of L&D care score (scale 0 to 100) based on adherence to L&D care standards, which had been introduced by the Ethiopian Ministry of Health in 2014.ResultsOn average, the hospitals met two-thirds of the standards for L&D care quality, with substantial variation between hospitals (standard deviation 10.9 percentage points). While the highest performing hospital met 91.3% of standards, the lowest performing hospital met only 35.8% of the standards. Hospitals had the highest adherence to standards in the domain of immediate and essential newborn care practices (86.8%), followed by the domain of care during the second and third stages of labour (77.9%). Hospitals scored substantially lower in the domains of active management of third stage of labour (AMTSL) (42.2%), interpersonal communication (47.2%), and initial assessment of the woman in labour (59.6%). We found the quality of L&D care score was significantly higher for women who had a history of any danger sign (β = 5.66; p-value = 0.001) and for women who were cared for at a teaching hospital (β = 12.10; p-value = 0.005). Additionally, hospitals with lower volume and more resources available for L&D care (P-values < 0.01) had higher L&D quality scores.ConclusionsOverall, the quality of L&D care provided to labouring mothers at government hospitals in SNNPR was limited. Lack of adherence to standards in the areas of the critical tasks of initial assessment, AMTSL, interpersonal communication during L&D, and respect for women’s preferences are especially concerning. Without greater attention to the quality of L&D care, regardless of how accessible hospital L&D care becomes, maternal and neonatal mortality rates are unlikely to decrease substantially.

The chapter summarizes key literature, including emerging ideas, that is pertinent to the question of how organizations and their leadership deal with and are resilient through crises - highlighting what works in surviving unexpected crises. The chapter presents an illustration of organizational response; it concludes with an analysis of what is missing from the literature and recommends a path forward to expanding actionable knowledge in this area. Multiple, interdependent factors that foster resilience are identified including (1) being sensitive to possible threats - even seemingly small failures, (2) not relying on simple interpretations of events but rather seeking diversity to create a complete view of the environment, (3) leadership that embraces communication, transparency, and continuous learning, (4) valuing expertise and allowing expert staff to make decisions during a crisis, and (5) a cultural commitment to a resiliency mindset that accepts failures as opportunities to learn and improve. Emerging concepts that may foster resilience but require more research include managing paradox, emotional ambivalence and diversity. Additional areas for fruitful research include: the impact of short-term versus long-term, or successive, crises; external versus internal shocks and the framing of the source of shocks; how crisis affect the pace of innovation and change; the role of diversity in organizational responses to crises; and a set of methodological opportunities to leverage natural experiments or simulations in ways that allow for longitudinal data illuminating the full cycle of crises across organizations from anticipation, to response, to longer-term adaptation to the new normal.

Patients with receding or high hairlines have traditionally been considered unfavorable candidates for endoscopic brow lift as this can further lengthen the hairline. We analyzed outcomes in patients that underwent a novel endoscopic brow lift technique with placement of incisions and anchoring Endotine Forehead Devices (CoApt Systems Inc, Palo Alto, CA, USA) directly at the natural forehead crease lines, in an effort to minimize elevation of the hairline, whereas providing well-hidden scars. We retrospectively reviewed all patients who underwent this new Endotine and incision placement between 2016 and 2020. Preoperative and postoperative photographs of all patients were analyzed to determine the postoperative changes in brow elevation and forehead length proportion (defined as length from cranium to chin).The forehead length proportion was unchanged pre- and post-operatively, with no statistically significant differences noted (P = 0.48). The average brow position elevation ranged from 2.78 mm in the medial location to 5.05 mm in the lateral location. All patients were happy with their appearance and had improved visual fields postoperatively. The forehead scars healed well and were well hidden in forehead rhytids at long term follow-up.This novel endoscopic brow lift technique provides an option to utilize a minimally invasive approach in patients with receding hairline. With this technique, visible scars were minimized, whereas still being able to achieve reasonable brow elevation. Thus, our approach enables long term maintenance of brow elevation with inconspicuous scars in the forehead.

There is currently no universally accepted name for inflammatory disease of the eye and orbit associated with thyroid autoimmune disease. Variability in terminology impedes the evaluation of scientific literature and clinical collaboration and can affect patients’ understanding of a disease process. The goals of this perspective article are 1. To compare the frequency of different terms used for eye disease associated with autoimmune thyroid disease in the scientific literature between 2000, 2010 and 2020 publications; 2. To investigate potential associations of terminology with author and journal specialty, and multidisciplinary vs. mono-disciplinary author teams; 3. To determine preferential terms used by professional societies; and 4. To propose standardized terminology based on our data analysis. The methods for this study included review of all English language articles listed in PubMed, with publication dates in the years 2000, 2010 and 2020, that included one of 6 terms currently used to describe eye disease associated with autoimmune thyroid disease. Characteristics pertaining to authors, journals, and article type were recorded. Results showed that the most used term in the 2000 literature was Graves’ Ophthalmopathy (61%). In the 2010 literature, Graves’ Orbitopathy (31%) became most common, followed by Graves’ Ophthalmopathy (30%). Between 2010 and 2020, thyroid eye disease (37%) became the most common term, followed by Graves’ Orbitopathy (35%). This perspective article proposes “thyroid eye disease” (TED) as the preferred name for this entity and discusses supporting terminology patterns and trends over time in scientific literature and in professional societies.

The rapid expansion of entrustable professional activity (EPA) assessment programs has led to calls to ensure fidelity in implementation and integrity in meeting the goals of competency-based medical education. Initiated in July 2017, in advance of the articulated core components of EPA implementation, this article describes the structure and outcomes of the University of Virginia (UVA) EPA Program and provides support for the identified essential components.The UVA EPA Program includes workplace assessments by residents/fellows, attending faculty, and master assessors (MAs), experienced clinicians who assess students across disciplines and clinical settings. All assessors participate in formal professional development and provide verbal and written comments to support their supervision ratings. The Entrustment Committee, composed of 12 MAs, uses a shared mental model and aggregates all assessor data to make a high-stakes summative entrustment decision about students' readiness to assume the role of an acting intern.Since 2017, over 2,000 assessors have completed 56,969 EPA assessments for 1,479 students. Ninety-four percent of assessments have been done during the clerkship phase. Residents/fellows have completed a mean of 18 assessments, attending faculty a mean of 27, and MAs a mean of 882. Seventy-four percent of observed encounters involved patients with acute concerns with or without a co-morbid condition. Fifty percent of assessments occurred in inpatient and 32% in ambulatory settings. Eighty-seven percent of assessments contained narrative comments with more than 100 characters.Planned next steps will include earlier identification of students who require individualized learning to promote the development of skills related to EPAs, expansion of the remediation program to enable more students to engage in a clinical performance mastery elective, and creation of targeted professional development for assessors to reinforce the tenets of the EPA program.

In increasingly diverse schools, teachers are challenged to effectively instruct students with a wide range of disabilities. Yet, preservice training and hands on experience in instructing students with disabilities are limited; many new teachers report a lack of sufficient training in working with diverse students. Frequent opportunities for practice are important in successfully preparing preservice teachers; however, budget and time constraints make ample opportunities for practice difficult. Simulations can provide a safe and controlled environment for teachers to engage in frequent practice and receive immediate feedback. The simulations in this article cover a wide variety of disabilities that educators could encounter with students in the classroom. These simulations can help raise empathy, awareness, and improve student-teacher relationships while helping teachers create a classroom environment that is conducive to learning for all students.

Periorbital hemorrhage is a potentially sight threatening surgical complication. The effect of new oral anticoagulants (NOACs) on hemorrhagic events after periorbital surgery has not been investigated. We describe four cases of severe delayed postoperative hemorrhage associated with NOACs, in addition to three cases in patients on traditional antithrombotic agents. Time of delayed hemorrhage ranged from postoperative day 2 to 6. Six patients required surgical intervention to achieve control of bleeding, and two patients required transfusion of blood products. Risk factors and management of this rare complication are discussed.

Studies using data from before 2011 concluded that the cost of US cancer care is justified given improved outcomes compared with European countries. However, it is unclear whether contemporary US cancer care provides better value than that of other high-income countries.To assess whether cancer mortality rates in 2020 were lower in countries with higher cancer-related spending, and to estimate across countries the incremental cost per averted cancer death.Cross-sectional, national-level analysis of 22 high-income countries, assessing the association between cancer care expenditures and age-standardized population-level cancer mortality rates in 2020, with and without adjustment for smoking. In addition, US incremental costs per averted death compared with the other countries were calculated. This study was conducted from September 1, 2021, to March 31, 2022.Age-standardized population-level cancer mortality rates.In this cross-sectional study of 22 countries, the median cancer mortality rate was 91.4 per 100 000 population (IQR, 84.2-101.6). The US cancer mortality rate was higher than that of 6 other countries (86.3 per 100 000). Median per capita spending in USD for cancer care was $296 (IQR, $222-$348), with the US spending more than any other country ($584). After adjusting for smoking, 9 countries had lower cancer care expenditures and lower mortality rates than the US. Of the remaining 12 countries, the US additionally spent more than $5 million per averted death relative to 4 countries, and between $1 and $5 million per averted death relative to 8 countries. Cancer care expenditures were not associated with cancer mortality rates, with or without adjustment for smoking (PearsonIn this cross-sectional study of national cancer care expenditures and cancer mortality rates across 22 countries, although the cancer mortality rate in the US was lower than the median, the US spent twice as much on cancer care as the median country. Findings of this study suggest that the US expenditure on cancer care may not be commensurate with improved cancer outcomes.

Higher education has been touted as critical to social mobility, even greater longevity; however, these benefits accrue with degree completion, and many students who begin college never earn a degree. Using the most recent Integrated Postsecondary Education Data System (IPEDS), we sought to understand variation in college completion rates and test hypotheses related to a set of institutional factors potentially associated with higher completion rates. Our findings suggest that greater attention to low-resource institutions is paramount if higher education is to fulfill the aspiration of promoting social mobility and equity. Several policy interventions could be used to combat ongoing disparities.

Outpatient visits and surgeries for nonurgent indications in ophthalmology have intermittently been restricted during the COVID-19 pandemic. Telemedicine services have rapidly gained acceptance during this period, and could improve patient access for routine oculoplastic evaluations in the future. The objective of this study is to investigate interobserver and intraobserver reliability of eyelid and brow position assessment and surgical plan when comparing photography-based and face-to-face evaluation.This was an observational study conducted at a single academic center. Thirty randomly selected patients who had completed an in-office evaluation for chief complaint of "drooping eyelids" between June 2019 and March 2020 were included. Virtual assessment of brow position, dermatochalasis, blepharoptosis, and margin-reflex distance 1 was performed by 2 oculoplastic surgeons based on external photographs, and a surgical plan was formulated. Fraction of agreement and Cohen's κ were determined to evaluate reliability of the virtual assessment compared to face-to-face examination.For 60 eyes from 30 study subjects, diagnostic reliability for observer A was near perfect for brow ptosis, substantial for blepharoptosis and moderate for dermatochalasis (κ = 0.86, 0.67, and 0.57, respectively); for observer B, reliability was moderate for brow and blepharoptosis and substantial for dermatochalasis (0.47, 0.59, and 0.79). Fraction of agreement for blepharoptosis was 94% in eyes where the eyelid margin was visible, and 66% in eyes where the eyelid margin was obscured by overhanging skin. Virtual margin-reflex distance 1 measurements were highly correlated with those obtained face to face (r = 0.77, p0.01). Fraction of agreement for surgical plan after virtual examination by observer A/B, respectively, was 100%/94% for brow lift, 90%/87% for blepharoptosis repair and 83%/83% for functional upper blepharoplasty.Virtual evaluation of upper eyelid and brow malposition can be performed with acceptable reliability. Co-existing dermatochalasis or brow ptosis may require special photographic technique or video examination to ensure an appropriate diagnosis. A photography-based preliminary surgical plan offers a viable alternative to face-to-face encounters.

Long bones are formed and repaired through the process of endochondral ossification. Activation of G protein-coupled receptor (GPCR) signaling pathways is crucial for skeletal development and long bone growth. G protein-gated inwardly-rectifying K(+) (GIRK) channel genes are key functional components and effectors of GPCR signaling pathways in excitable cells of the heart and brain, but their roles in non-excitable cells that directly contribute to endochondral bone formation have not been studied. In this study, we analyzed skeletal phenotypes of Girk2(−/−), Girk3(−/−) and Girk2/3(−/−) mice. Bones from 12-week-old Girk2(−/−) mice were normal in length, but femurs and tibiae from Girk3(−/−) and Girk2/3(−/−) mice were longer than age-matched controls at 12-weeks-old. Epiphyseal chondrocytes from 5-day-old Girk3(−/−) mice expressed higher levels of genes involved in collagen chain trimerization and collagen fibril assembly, lower levels of genes encoding VEGF receptors, and produced larger micromasses than wildtype chondrocytes in vitro. Girk3(−/−) chondrocytes were also more responsive to the kappa opioid receptor (KOR) ligand dynorphin, as evidenced by greater pCREB expression, greater cAMP and GAG production, and upregulation of Col2a1 and Sox9 transcripts. Imaging studies showed that Kdr (Vegfr2) and endomucin expression was dramatically reduced in bones from young Girk3(−/−) mice, supporting a role for delayed vasculogenesis and extended postnatal endochondral bone growth. Together these data indicate that GIRK3 controls several processes involved in bone lengthening.

The intervertebral disc (IVD) aids in motion and acts to absorb energy transmitted to the spine. With little inherent regenerative capacity, degeneration of the intervertebral disc results in intervertebral disc disease, which contributes to low back pain and significant disability in many individuals. Increasing evidence suggests that IVD degeneration is a disease of the whole joint that is associated with significant inflammation. Moreover, studies show elevated macrophage accumulation within the IVD with increasing levels of disease severity; however, we still need to understand the roles, be they causative or consequential, of macrophages during the degenerative process. In this narrative review, we discuss hallmarks of IVD degeneration, showcase evidence of macrophage involvement during disc degeneration, and explore burgeoning research aimed at understanding the molecular pathways regulating macrophage functions during intervertebral disc degeneration.

Francisella tularensis(F. tularensis) is a Gram-negative, intracellular bacterium and the causative agent of a fatal human disease known as tularemia. The CDC has classifiedF. tularensisas a Tier 1 Category A select agent based on its ease of aerosolization, low infectious dose, past use as a bioweapon, and the potential to be used as a bioterror agent.Francisellahas a unique replication cycle. Upon its uptake,Francisellaremains in the phagosomes for a short period and then escapes into the cytosol, where the replication occurs.Francisellais recognized by cytosolic pattern recognition receptors, Absent In Melanoma 2 (Aim2) andNachtLRR andPYD domains containing Protein3(Nlrp3). The recognition ofFrancisellaligands by Aim2 and Nlrp3 triggers the assembly and activation of the inflammasome. The mechanism of activation of Aim2 is well established; however, how Nlrp3 inflammasome is activated in response toF. tularensisinfection is not known. Unlike Aim2, the protective role of Nlrp3 againstFrancisellainfection is not fully established. This study investigated the role of Nlrp3 and the potential mechanisms through which Nlrp3 exerts its detrimental effects on the host in response toF. tularensisinfection. The results fromin vitrostudies demonstrate that Nlrp3 dampens NF-κB and MAPK signaling, and pro-inflammatory cytokine production, which allows replication ofF. tularensisin infected macrophages.In vivo, Nlrp3 deficiency results in differential expression of several genes required to induce a protective immune response against respiratory tularemia. Nlrp3-deficient mice mount a stronger innate immune response, clear bacteria efficiently with minimal organ damage, and are more resistant toFrancisellainfection than their wild-type counterparts. Together, these results demonstrate that Nlrp3 enhances the host’s susceptibility toF. tularensisby modulating the protective innate immune responses. Collectively, this study advances our understanding of the detrimental role of Nlrp3 in tularemia pathogenesis.

Background Ethiopia has low skilled birth attendance rates coupled with low quality of care within health facilities contributing to one of the highest maternal mortality rates in Sub-Saharan Africa, at 412 deaths per 100,000 live births. There is lack of evidence on the readiness of health facilities to deliver quality labor and delivery (L&D) care. This paper describes the structural quality of routine L&D care in government hospitals of Ethiopia. Methods A facility-based cross-sectional study design, involving census of all government hospitals in Southern Nations Nationalities and People’s Region (SNNPR) (N = 20) was conducted in November 2016 through facility audit using a structured checklist. Data collectors verified the availability and functioning of the required items through observation and interview with the heads of labor and delivery case team. An overall mean score of structural quality was calculated considering domain scores such as general infrastructure, human resource and essential drugs, supplies, equipment and laboratory services. Summary statistics such as proportion, mean and standard deviation were computed to describe the degree of adherence of the hospitals to the standards related to structural quality of routine labor and delivery care. Results One third of hospitals had low readiness to provide quality routine L&D care, with only two approaching near fulfilment of all the standards. Hospitals had fulfilled 68.2% of the standards for the structural aspects of quality of L&D care. Of the facility audit criteria, the availability of essential equipment and supplies for infection prevention scored the highest (88.8%), followed by safety, comfort and woman friendliness of the environment (76.4%). Availability skilled health professionals and quality management practices scored 72.5% each, while availability of the required items of general infrastructure was 64.6%. The two critical domains with the lowest score were availability of essential drugs, supplies and equipment (52.2%); and laboratory services and safe blood supply (50%). Conclusion Substantial capacity gaps were observed in the hospitals challenging the provision of quality routine L&D care services, with only two thirds of required resources available. The largest gaps were in laboratory services and safe blood, and essential drugs, supplies and equipment. The results suggest the need to ensure that all public hospitals in SNNPR meet the required structure to enable the provision of quality routine L&D care with emphases on the identified gaps.

Prior work demonstrated that Phlpp1 deficiency alters trabecular bone mass and enhances M-CSF responsiveness, but the cell types and requirement of Phlpp1 for this effect were unclear. To understand the function of Phlpp1 within myeloid lineage cells, we crossed Phlpp1 floxed mice with mice harboring LysM-Cre. Micro-computed tomography of the distal femur of 12-week-old mice revealed a 30% increase in bone volume per total volume of Phlpp1 female conditional knockouts, but we did not observe significant changes within male Phlpp1 cKOLysM mice. Bone histomorphmetry of the proximal tibia further revealed that Phlpp1 cKOLysM females exhibited elevated osteoclast numbers, but conversely had reduced levels of serum markers of bone resorption as compared to littermate controls. Osteoblast number and serum markers of bone formation were unchanged. In vitro assays confirmed that Phlpp1 ablation enhanced osteoclast number and area, but limited bone resorption. Additionally, reconstitution with exogenous Phlpp1 suppressed osteoclast numbers. Dose response assays demonstrated that Phlpp1−/− cells are more responsive to M-CSF, but reconstitution with Phlpp1 abrogated this effect. Furthermore, small molecule-mediated Phlpp inhibition enhanced osteoclast numbers and size. Enhanced phosphorylation of Phlpp substrates—including Akt, ERK1/2, and PKCζ—accompanied these observations. In contrast, actin cytoskeleton disruption occurred within Phlpp inhibitor treated osteoclasts. Moreover, Phlpp inhibition reduced resorption of cells cultured on bovine bone slices in vitro. Our results demonstrate that Phlpp1 deficiency within myeloid lineage cells enhances bone mass by limiting bone resorption while leaving osteoclast numbers intact, moreover, we show that Phlpp1 represses osteoclastogenesis and controls responses to M-CSF.

Prior work demonstrated that Phlpp1 deficiency alters trabecular bone mass and enhances M-CSF responsiveness, but the cell types and requirement of Phlpp1 for this effect were unclear. To understand the function of Phlpp1 within myeloid lineage cells, we crossed Phlpp1 floxed mice with mice harboring LysM-Cre. Micro-computed tomography of the distal femur of 12-week-old mice revealed a 30% increase in bone volume per total volume of Phlpp1 female conditional knockouts, but we did not observe significant changes within male Phlpp1 cKOLysM mice. Bone histomorphmetry of the proximal tibia further revealed that Phlpp1 cKOLysM females exhibited elevated osteoclast numbers, but conversely had reduced levels of serum markers of bone resorption as compared to littermate controls. Osteoblast number and serum markers of bone formation were unchanged. In vitro assays confirmed that Phlpp1 ablation enhanced osteoclast number and area, but limited bone resorption. Additionally, reconstitution with exogenous Phlpp1 suppressed osteoclast numbers. Dose response assays demonstrated that Phlpp1−/− cells are more responsive to M-CSF, but reconstitution with Phlpp1 abrogated this effect. Furthermore, small molecule-mediated Phlpp inhibition enhanced osteoclast numbers and size. Enhanced phosphorylation of Phlpp substrates—including Akt, ERK1/2, and PKCζ—accompanied these observations. In contrast, actin cytoskeleton disruption occurred within Phlpp inhibitor treated osteoclasts. Moreover, Phlpp inhibition reduced resorption of cells cultured on bovine bone slices in vitro. Our results demonstrate that Phlpp1 deficiency within myeloid lineage cells enhances bone mass by limiting bone resorption while leaving osteoclast numbers intact; moreover, we show that Phlpp1 represses osteoclastogenesis and controls responses to M-CSF.

Back pain is a leading cause of global disability and is strongly associated with intervertebral disc (IVD) degeneration (IDD). Hallmarks of IDD include progressive cell loss and matrix degradation. The Akt signaling pathway regulates cellularity and matrix production in IVDs and its inactivation is known to contribute to a catabolic shift and increased cell loss via apoptosis. The PH domain leucine-rich repeat protein phosphatase (Phlpp1) directly regulates Akt signaling and therefore may play a role in regulating IDD, yet this has not been investigated. The aim of this study was to investigate if Phlpp1 has a role in Akt dysregulation during IDD. In human IVDs, Phlpp1 expression was positively correlated with IDD and the apoptosis marker cleaved Caspase-3, suggesting a key role of Phlpp1 in the progression of IDD. In mice, 3 days after IVD needle puncture injury, Phlpp1 knockout (KO) promoted Akt phosphorylation and cell proliferation, with less apoptosis. At 2 and 8 months after injury, Phlpp1 deficiency also had protective effects on IVD cellularity, matrix production, and collagen structure as measured with histological and immunohistochemical analyses. Specifically, Phlpp1-deletion resulted in enhanced nucleus pulposus matrix production and more chondrocytic cells at 2 months, and increased IVD height, nucleus pulposus cellularity, and extracellular matrix deposition 8 months after injury. In conclusion, Phlpp1 has a role in limiting cell survival and matrix degradation in IDD and research targeting its suppression could identify a potential therapeutic target for IDD.

Enhanced osteoclast-mediated bone resorption and diminished formation may promote bone loss. Pleckstrin homology (PH) domain and leucine-rich repeat protein phosphatase 1 (Phlpp1) regulates protein kinase C (PKC) and other proteins in the control of bone mass. Germline Phlpp1 deficiency reduces bone volume, but the mechanisms remain unknown. Here, we found that conditional Phlpp1 deletion in murine osteoclasts increases their numbers, but also enhances bone mass. Despite elevating osteoclasts, Phlpp1 deficiency did not increase serum markers of bone resorption, but elevated serum markers of bone formation. These results suggest that Phlpp1 suppresses osteoclast formation and production of paracrine factors controlling osteoblast activity. Phlpp1 deficiency elevated osteoclast numbers and size in ex vivo osteoclastogenesis assays, accompanied by enhanced expression of proto-oncogene C-Fms (C-Fms) and hyper-responsiveness to macrophage colony-stimulating factor (M-CSF) in bone marrow macrophages. Although Phlpp1 deficiency increased TRAP(+) cell numbers, it suppressed actin-ring formation and bone resorption in these assays. We observed that Phlpp1 deficiency increases activity of PKCζ, a PKC isoform controlling cell polarity, and that addition of a PKCζ pseudosubstrate restores osteoclastogenesis and bone resorption of Phlpp1-deficient osteoclasts. Moreover, Phlpp1 deficiency increased expression of the bone-coupling factor collagen triple helix repeat-containing 1 (Cthrc1). Conditioned growth medium derived from Phlpp1-deficient osteoclasts enhanced mineralization of ex vivo osteoblast cultures, an effect that was abrogated by Cthrc1 knockdown. In summary, Phlpp1 critically regulates osteoclast numbers, and Phlpp1 deficiency enhances bone mass despite higher osteoclast numbers because it apparently disrupts PKCζ activity, cell polarity, and bone resorption and increases secretion of bone-forming Cthrc1.

Case-control analysis and systematic literature review.To illustrate the prognosis and perioperative risk factors associated with this condition.Ischemic optic neuropathy (ION) is the most common pathological diagnosis underlying postoperative vision loss. It comes in two primary forms-anterior (AION)-affecting the optic disc or posterior (PION) affecting the optic nerve proximal to the disc. Spine surgery remains one of the largest sources of acute perioperative visual loss.We performed a 1:4 case-control analysis (by age and year of surgery) for patients with ION and those who didn't develop ION following spine surgery at our institution. A systematic literature search of Medline, Embase, Scopus from inception to September 2017 as also performed.We identified 12 cases from our institution. Comparison to 48 matched controls revealed fusion, higher number of operative levels, blood loss, and change in hemoglobin, hematocrit to be significantly associated with ION. Majority were diagnosed with PION (83%, 10/12) and had bilateral presentation (75%, 9/12). Only 30% patients (3/10) demonstrated improvement in visual acuity while the rest remained either unchanged (40%, 4/10) or worsened (20%, 2/10) at last follow-up. Literature review identified 182 cases from 42 studies. Posterior ischemic optic neuropathy (PION) was found in 58.7% (114/194) of cases, anterior ischemic optic neuropathy (AION) in 17% (33/19) and unspecified ION in 24% (47/194). PION was associated with higher odds of severe visual deficit at immediate presentation (odds ratio [OR]: 6.45, confidence interval [CI]: 1.04-54.3, P = 0.04) and last follow-up.PION is the most common cause of vision loss following spine surgery and causes more severe visual deficits compared with AION. Prone spine surgery especially multi-level fusions with longer operative time, higher blood loss, and intraoperative hypotension are most associated with the development of this devastating complication.3.

Suicide is a major public health issue and is the second leading cause of death among adolescents. Teachers are in an ideal position to screen and refer at-risk students, but most teachers have not received adequate training in this area. The purpose of this study was to assess the effectiveness of a computer simulation on training teachers in effective identification and referral practices for middle school students at-risk for bullying and suicidal ideation. Students in a Masters of Arts in Teaching (MAT) program in New York State completed At-Risk for Middle School Educators, a computer simulation created by Kognito Interactive that is intended to effectively train teachers in effective identification and referral practices for middle school students at-risk for bullying and suicidal ideation. Participants completed pre- and post-intervention surveys and participated in an online discussion of the simulation training. Results of a paired-samples t test indicated that At-Risk for Middle School Educators significantly improved the likelihood that teachers will recommend a student in distress for psychological services. It also significantly improved teacher confidence and competence in approaching and referring at-risk students to mental health services. Although the sample size was small and further research is warranted, results suggest that At-Risk for Middle School Educators is an effective training tool for educators in the area of the identification and referral of at-risk students.

Patients with syphilis can present with optic disc oedema (ODE) without visual compromise, which has been primarily attributed to papilloedema from raised intracranial pressure or optic perineuritis from optic nerve sheath inflammation. We report four cases of ODE in the setting of syphilis with preserved visual function, normal intracranial pressure, and no enhancement of the optic nerve or sheath on magnetic resonance imaging. We propose the term “incipient syphilitic papillitis” for cases presenting with ODE, preserved vision and absence of optic nerve sheath enhancement, which is likely a more common presentation than syphilitic optic perineuritis.

LGBTQ youth frequently experience bullying and harassment in the school setting. Teachers are in an ideal position to prevent student harassment, yet most don’t have adequate training. This study e...

Background There is robust preclinical literature and preliminary clinical findings supporting the use of N-Acetylcysteine (NAC) to treat substance use disorders, including tobacco use disorder (TUD). However, randomized controlled trials have yielded mixed results and NAC’s efficacy for TUD has not been established. The goals of this study were to assess the efficacy of NAC in promoting early and end-of-treatment abstinence and preventing relapse among adult smokers. Methods This randomized, double-blinded clinical trial enrolled adult, daily smokers (N = 114; ages 23–64; 51 % female; 65 % White; 29 % Black/African American; 7% Hispanic/Latinx), who were randomized 1:1 to receive NAC (n = 59) or placebo (n = 55) (1200 mg b.i.d.) for eight weeks. Participants received brief cessation counseling and incentives for abstinence during the first three days of the quit attempt. Primary outcomes: (i) carbon monoxide (CO)-confirmed abstinence during the first three days of the quit attempt. Secondary outcomes: (ii) time to relapse; (iii) biologically confirmed abstinence at Week 8. Results No differences were found between NAC and placebo groups on measures of early abstinence (3-day quit attempt; 11 % for NAC vs. 15 % for placebo; all p > 0.11), time to relapse (p = 0.19), and end-of-treatment abstinence (7% for NAC vs. 11 % for placebo; all p > 0.40]. Conclusions Results indicate that NAC is a well-tolerated pharmacotherapy but is unlikely to be efficacious as a monotherapy for TUD in adults. Considered in the collective context of other research, NAC may potentially be more useful in a younger population, as a combination pharmacotherapy, or in the presence of more intensive psychosocial treatment.

This chapter describes the principles of grand strategy as applied to global health and public health. It analyzes President George W. Bush's program, called the President's Emergency Plan for AIDS Relief (known as PEPFAR). Developed largely in secret and placed outside the traditional USAID bureaucracy, the PEPFAR program pole vaulted the United States into a leadership role in global health. The chapter then highlights how the use of grand strategic principles resulted in a highly successful, if still limited, global health intervention. The Bush Administration articulated explicit goals, or ends, and connected those to the larger ecology of national interests related to demonstrating American morality, and protecting the United States from the threat of pandemic HIV/AIDS. However, PEPFAR as a strategy was incomplete. It failed to address critical root causes of the spread of HIV/AIDS—the social and economic conditions in which such pathogens emerge and spread.

Previous studies examining the role of the histone deacetylase Hdac3 within myeloid cells demonstrated that Hdac3 promotes M2 activation and tissue healing in inflammatory conditions. Since myeloid lineage cells are required for proper bone formation and regeneration, in this study we examined the functions of Hdac3 during bone healing. Conditional deletion of Hdac3 within myeloid progenitors accelerates healing of cortical bone defects. Moreover, reduced osteoclast numbers within the defect site are correlated with Hdac3 suppression. Ex vivo osteoclastogenesis assays further demonstrate that Hdac3 deficiency limits osteoclastogenesis, the number of nuclei per cell and bone resorption, suggesting a defect in cell fusion. High throughput RNA sequencing identified the transmembrane protein Pmepa1 as a differentially expressed gene within osteoclast progenitor cells. Knockdown of Pmepa1 partially restores defects in osteoclastogenesis induced by Hdac3 deficiency. These results show that Hdac3 is required for optimal bone healing and osteoclast fusion, potentially via its regulation of Pmepa1 expression.

Prior studies demonstrated that deletion of the protein phosphatase Phlpp1 in Ctsk-Cre expressing cells enhances bone mass, characterized by diminished osteoclast activity and increased coupling to bone formation. Due to non-specific expression of Ctsk-Cre, the definitive mechanism for this observation was unclear. To further define the role of bone resorbing osteoclasts, we performed ovariectomy (Ovx) and Sham surgeries on Phlpp1 cKOCtsk and WT mice. Micro-CT analyses confirmed enhanced bone mass of Phlpp1 cKOCtsk Sham females. In contrast, Ovx induced bone loss in both groups, with no difference between Phlpp1 cKOCtsk and WT mice. Histomorphometry demonstrated that Ovx mice lacked differences in osteoclasts per bone surface, suggesting that estradiol (E2) is required for Phlpp1 deficiency to have an effect. We performed high throughput unbiased transcriptional profiling of Phlpp1 cKOCtsk osteoclasts and identified 290 differentially expressed genes. By cross-referencing these differentially expressed genes with all estrogen response element (ERE) containing genes, we identified IGFBP4 as potential estrogen-dependent target of Phlpp1. E2 induced PHLPP1 expression, but reduced IGFBP4 levels. Moreover, genetic deletion or chemical inhibition of Phlpp1 was correlated with IGFBP4 levels. We then assessed IGFBP4 expression by osteoclasts in vivo within intact 12-week-old females. Modest IGFBP4 immunohistochemical staining of TRAP+ osteoclasts within WT females was observed. In contrast, TRAP+ bone lining cells within intact Phlpp1 cKOCtsk females robustly expressed IGFBP4, but levels were diminished within TRAP+ bone lining cells following Ovx. These results demonstrate that effects of Phlpp1 conditional deficiency are lost following Ovx, potentially due to estrogen-dependent regulation of IGFBP4.

Musculoskeletal pain contributes significantly to chronic pain experienced by adults and to health care use. This chapter details several methods to evaluate pain and physical activity in mice that can be applied to preclinical orthopedic models. These methods include the von Frey filament assay that measures mechanical allodynia, open-field activity assays for evaluation of ambulation, and incapacitance measurements to determine static weight bearing.

Musculoskeletal pain contributes significantly to chronic pain experienced by adults and to health care use. This chapter details several methods to evaluate pain and physical activity in mice that can be applied to preclinical orthopedic models. These methods include the von Frey filament assay that measures mechanical allodynia, open-field activity assays for evaluation of ambulation, and incapacitance measurements to determine static weight bearing.

Evidence regarding the role of nurses-in-leadership and how to engage nurses in policy decisions is minimal in sub-Saharan Africa. The purpose of this study was: (1) to assess the leadership practices of nurses-in-leadership in Uganda (by self-report) and from the perspective of ‘followers’ (direct-report, peers, co-workers, other); and (2) to determine factors (positively) associated with leadership practices. We surveyed 480 nurses, 120 in leadership roles (Response Rate 57%) and 360 ‘followers’ (Response Rate 60%), who were recruited from five hospitals in Kampala, Uganda. We used the Leadership Practice Inventory (Self and Observer), a project-specific demographic questionnaire and Denison’s Organizational Culture Survey (DOCS). Sixty-three per cent of the respondents held a registered nursing certificate; 79% had received formal leadership training; 47% were based in private for-profit (PFP) hospitals, 28% in private not-for-profit (PNFP) and 25% in public hospitals. Among the five leadership practices, nurses-in-leadership used the practice of Model the Way (M = 8.27, SD = 1.30), Challenge the Process (M = 8.12, SD = 1.30) and Encourage the Heart (M = 8.04, SD = 1.51) more frequently (on a 10-point Likert Scale). Inspire a Shared Vision (M = 7.82, SD = 1.57) and Enable Others to Act (M = 7.62, SD = 1.66) practices were used less frequently. The same rank order was true for leadership scores from the perception of followers. However, leadership scores by followers were significantly lower (P

This chapter discusses the shortcomings of the current global health regime and proposes a new framework based on Woodrow Wilson’s ideas about global interaction and responsibility. The authors explain how critical it is to establish a successful new system, given climate change, microbial evolution, and the current political landscape. The proposed system must resolve the tension between national sovereignty and national interdependence, while also improving response time and investing in long-term solutions. The authors conclude that these guidelines can be met by introducing engaged pluralism and ambidextrous leadership.