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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.

To determine if tangent visual fields gathered during assessment of superior visual field deficits caused by blepharoptosis and dermatochalasis offer good correlation to clinical exam in a time and cost efficient manner.Prospective, observational case series. Subjects included all patients referred to a single surgeon (CCN) who underwent surgical correction of blepharoptosis and/or dermatochalasis. Preoperatively and postoperatively, upper margin-to-reflex distances were assessed. Tangent visual fields were performed in a timed fashion and analyzed for degrees of intact vision in the vertical meridian and degrees squared of area under the curve. Data were compared by Student t-tests and Pearson correlation coefficients.Mean preoperative superior visual fields with the eyelid in the natural position measured 8° in the vertical meridian. Measurements in the vertical meridian and area under the curve showed excellent correlation (r = 0.87). Patients with ptosis showed strong correlation between margin-to-reflex distance and superior visual fields. Patients completed field testing faster than reported times for automated or Goldmann testing. Finally, tangent screens were the least expensive type of equipment to purchase.Tangent visual fields are a rapid and inexpensive way to test for functional loss of superior visual field in patients with upper eyelid malposition. Our data revealed potential differences between tangent screen results and published results for automated or Goldmann visual field testing which warrants further studies.

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-level 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 to which the hospital met the 2014 Ethiopian Ministry of Health standards regarding to resources available for providing quality of L&D care (measured on a 0-100% scale). These standards pertain to availability of human resource by category and training status, availability of essential drugs, supplies and equipment in L&D ward, availability of laboratory services and safe blood, and availability of essential guidelines for key L&D care processes.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.

Intervertebral disc (IVD) degeneration is a common pathological condition associated with low back pain. Recent evidence suggests that mesenchymal signaling cells (MSCs) promote IVD regeneration, but underlying mechanisms remain poorly defined. One postulated mechanism is via modulation of macrophage phenotypes. In this manuscript, we tested the hypothesis that MSCs produce trophic factors that alter macrophage subsets. To this end, we collected conditioned medium from human, bone marrow-derived STRO3+ MSCs. We then cultured human bone marrow-derived macrophages in MSC conditioned medium (CM) and performed single cell RNA-sequencing. Comparative analyses between macrophages cultured in hypoxic and normoxic MSC CM showed large overlap between macrophage subsets; however, we identified a unique hypoxic MSC CM-induced macrophage cluster. To determine if factors from MSC CM simulated effects of the anti-inflammatory cytokine IL-4, we integrated the data from macrophages cultured in hypoxic MSC CM with and without IL-4 addition. Integration of these data sets showed considerable overlap, demonstrating that hypoxic MSC CM simulates the effects of IL-4. Interestingly, macrophages cultured in normoxic MSC CM in the absence of IL-4 did not significantly contribute to the unique cluster within our comparison analyses and showed differential TGF-β signaling; thus, normoxic conditions did not approximate IL-4. In addition, TGF-β neutralization partially limited the effects of MSC CM. In conclusion, our study identified a unique macrophage subset induced by MSCs within hypoxic conditions and supports that MSCs alter macrophage phenotypes through TGF-β-dependent mechanisms.

Circadian regulation of gene expression is prevalent and plays critical roles in cell differentiation. However, its roles in the reprogramming of differentiated cells remain largely unknown. Here, we found that one of the master circadian regulators PER1 promoted virus-mediated reprogramming of mouse embryonic fibroblasts (MEFs) to induced neurons (iNs) and induced pluripotent stem cells (iPSCs). Unexpectedly, PER1 achieved this by repressing inflammatory activation of contaminating macrophages in the MEF culture, rather than by directly modulating the reprogrammability of MEFs. More specifically, we found that transduced viruses activated inflammatory genes in macrophages, such as Tnf encoding TNFα, one of the central inflammatory regulators and an autocrine activator of macrophages. TNFα inhibited iN reprogramming, whereas a TNFα inhibitor promoted iN reprogramming, connecting the inflammatory responses to iN reprogramming. In addition, macrophages were induced to proliferate and mature by non-macrophage cells serving as feeders, which also supported up-regulation of TNFα in macrophages without virus transduction. Furthermore, the 2 inflammatory responses were repressed by the circadian regulator PER1 in macrophages, making reprogrammability dependent on time-of-day of virus transduction. Similar results were obtained with iPSC reprogramming, suggesting a wide occurrence of macrophage-mediated inhibition of cell reprogramming. This study uncovers mechanistic links between cell reprogramming, bystander inflammatory macrophages, and circadian rhythms, which are particularly relevant to in vivo reprogramming and organoid formation incorporating immune cells.

ABSTRACT Prior work demonstrated that Phlpp1 deficiency alters limb length and bone mass, but the cell types involved and requirement of Phlpp1 for this effect were unclear. To understand the function of Phlpp1 within bone‐forming osteoblasts, we crossed Phlpp1 floxed mice with mice harboring type 1 collagen (Col1a12.3kb)‐Cre. Mineralization of bone marrow stromal cell cultures derived from Phlpp1 cKOCol1a1 was unchanged, but levels of inflammatory genes (eg, Ifng, Il6, Ccl8) and receptor activator of NF‐κB ligand/osteoprotegerin (RANKL/OPG) ratios were enhanced by either Phlpp1 ablation or chemical inhibition. Micro‐computed tomography of the distal femur and L5 vertebral body of 12‐week‐old mice revealed no alteration in bone volume per total volume, but compromised femoral bone microarchitecture within Phlpp1 cKOCol1a1 conditional knockout females. Bone histomorphometry of the proximal tibia documented no changes in osteoblast or osteoclast number per bone surface but slight reductions in osteoclast surface per bone surface. Overall, our data show that deletion of Phlpp1 in type 1 collagen–expressing cells does not significantly alter attainment of peak bone mass of either males or females, but may enhance inflammatory gene expression and the ratio of RANKL/OPG. Future studies examining the role of Phlpp1 within models of advanced age, inflammation, or osteocytes, as well as functional redundancy with the related Phlpp2 isoform are warranted. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Abstract 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.

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.

Leptospirosis is a zoonotic disease of global importance with significant morbidity and mortality. However, the disease is frequently overlooked and underdiagnosed, leading to uncertainty of the true scale and severity of the disease. A neglected tropical disease, leptospirosis disproportionately impacts disadvantaged socioeconomic communities most vulnerable to outbreaks of zoonotic disease, due to contact with infectious animals and contaminated soils and waters. With growing evidence that Leptospira survives, persists, and reproduces in the environment, this paper reviews the current understanding of the pathogen in the environment and highlights the unknowns that are most important for future study. Through a systematic Boolean review of the literature, our study finds that detailed field-based study of Leptospira prevalence, survival, and transmission in natural waters and soils is lacking from the current literature. This review identified a strong need for assessment of physical characteristics and biogeochemical processes that support long-term viability of Leptospira in the environment followed by epidemiological assessment of the transmission and movement of the same strains of Leptospira in the present wildlife and livestock as the first steps in improving our understanding of the environmental stage of the leptospirosis transmission cycle.

Abstract 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.

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 classified F. tularensis as 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. Francisella has a unique replication cycle. Upon its uptake, Francisella remains in the phagosomes for a short period and then escapes into the cytosol, where the replication occurs. Francisella is recognized by cytosolic pattern recognition receptors, Absent In Melanoma 2 (Aim2) and Nacht LRR and PYD domains containing Protein 3 (Nlrp3). The recognition of Francisella ligands 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 to F. tularensis infection is not known. Unlike Aim2, the protective role of Nlrp3 against Francisella infection 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 to F. tularensis infection. The results from in vitro studies demonstrate that Nlrp3 dampens NF-κB and MAPK signaling, and pro-inflammatory cytokine production, which allows replication of F. tularensis in 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 to Francisella infection than their wild-type counterparts. Together, these results demonstrate that Nlrp3 enhances the host’s susceptibility to F. tularensis by modulating the protective innate immune responses. Collectively, this study advances our understanding of the detrimental role of Nlrp3 in tularemia pathogenesis.

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.

Despite international recognition of the importance of healthcare management in the development of high-performing systems, the path by which countries may develop and sustain a professional healthcare management workforce has not been articulated. Accordingly, we sought to identify a set of common themes in the establishment of a professional workforce of healthcare managers in low- and middle-income country (LMIC) settings using a descriptive case study approach. We draw on a historical analysis of the development of this profession in the United States and Ethiopia to identify five common themes in the professionalization of healthcare management: (1) a country context in which healthcare management is demanded; (2) a national framework that elevates a professional management role; (3) standards for healthcare management, and a monitoring function to promote adherence to standards; (4) a graduatelevel educational path to ensure a pipeline of well-prepared healthcare managers; and (5) professional associations to sustain and advance the field. These five components can to inform the creation of a long-term national strategy for the development of a professional cadre of heathcare managers in LMIC settings.

Strengthening district-level management may be an important lever for improving key public health outcomes in low-income settings; however, previous studies have not established the statistical associations between better management and primary healthcare system performance in such settings. To explore this gap, we conducted a cross-sectional study of 36 rural districts and 226 health centers in Ethiopia, a country which has made ambitious investment in expanding access to primary care over the last decade. We employed quantitative measure of management capacity at both the district health office and health center levels and used multiple regression models, accounting for clustering of health centers within districts, to estimate the statistical association between management capacity and a key performance indicator (KPI) summary score based on antenatal care coverage, contraception use, skilled birth attendance, infant immunization, and availability of essential medications. In districts with above median district management capacity, health center management capacity was strongly associated (p < 0.05) with KPI performance. In districts with below median management capacity, health center management capacity was not associated with KPI performance. Having more staff at the district health office was also associated with better KPI performance (p < 0.05) but only in districts with above median management capacity. The results suggest that district-level management may provide an opportunity for improving health system performance in low-income country settings.

Abstract Many countries struggle to develop and implement strategies to monitor hospitals nationally. The challenge is particularly acute in low-income countries where resources for measurement and reporting are scarce. We examined the experience of developing and implementing a national system for monitoring the performance of 130 government hospitals in Ethiopia. Using participatory observation, we found that the monitoring system resulted in more consistent hospital reporting of performance data to regional health bureaus and the federal government, increased transparency about hospital performance and the development of multiple quality-improvement projects. The development and implementation of the system, which required technical and political investment and support, would not have been possible without strong hospital-level management capacity. Thorough assessment of the health sector's readiness to change and desire to prioritize hospital quality can be helpful in the early stages of design and implementation. This assessment may include interviews with key informants, collection of data about health facilities and human resources and discussion with academic partners. Aligning partners and donors with the government's vision for quality improvement can enhance acceptability and political support. Such alignment can enable resources to be focused strategically towards one national effort - rather than be diluted across dozens of potentially competing projects. Initial stages benefit from having modest goals and the flexibility for continuous modification and improvement, through active engagement with all stakeholders.