Implementation and evaluation of a Project ECHO telementoring program for the Namibian HIV workforce.

BACKGROUND: The Namibian Ministry of Health and Social Services (MoHSS) piloted the first HIV Project ECHO (Extension for Community Health Outcomes) in Africa at 10 clinical sites between 2015 and 2016. Goals of Project ECHO implementation included strengthening clinical capacity, improving professional satisfaction, and reducing isolation while addressing HIV service challenges during decentralization of antiretroviral therapy. METHODS: MoHSS conducted a mixed-methods evaluation to assess the pilot. Methods included pre/post program assessments of healthcare worker knowledge, self-efficacy, and professional satisfaction; assessment of continuing professional development (CPD) credit acquisition; and focus group discussions and in-depth interviews. Analysis compared the differences between pre/post scores descriptively. Qualitative transcripts were analyzed to extract themes and representative quotes. RESULTS: Knowledge of clinical HIV improved 17.8% overall (95% confidence interval 12.2-23.5%) and 22.3% (95% confidence interval 13.2-31.5%) for nurses. Professional satisfaction increased 30 percentage points. Most participants experienced reduced professional isolation (66%) and improved CPD credit access (57%). Qualitative findings reinforced quantitative results. Following the pilot, the Namibia MoHSS Project ECHO expanded to over 40 clinical sites by May 2019 serving more than 140 000 people living with HIV. CONCLUSIONS: Similar to other Project ECHO evaluation results in the United States of America, Namibia's Project ECHO led to the development of ongoing virtual communities of practice. The evaluation demonstrated the ability of the Namibia HIV Project ECHO to improve healthcare worker knowledge and satisfaction and decrease professional isolation.

Oral narratives in monolingual and bilingual preschoolers with SLI.

BACKGROUND: The body of literature on narratives of bilingual children with and without specific language impairment (SLI) is growing. However, little is known about the narrative abilities of bilingual preschool children with SLI and their patterns of growth. AIMS: To determine the similarities and differences in narrative abilities between preschoolers with and without SLI who are either monolingual or bilingual at two time points. METHODS & PROCEDURES: Forty children completed a narrative retell task in English at two test points. The mean ages were 52 and 58 months at Times 1 and 2, respectively. We examined performance on measures of narrative macrostructure (narrative information) and microstructure (sentence length, number of different words, verb accuracy, first mentions) in monolingual and bilingual children with and without SLI. The bilingual children were from diverse first-language backgrounds and all spoke English most of the time. OUTCOMES & RESULTS: A series of repeated-measures analyses of variance was used with language ability (typical development or SLI) and bilingual status (monolingual versus bilingual) as the between-subjects factors and time (Times 1 or 2) as the within-subjects factor. Results indicated a significant main effect of time for four measures (i.e., Information Score, lexical diversity, sentence length and verb accuracy). The between-subjects analyses indicated a significant difference between the typically developing children and the children with SLI in all measures and a significant difference between monolingual and bilingual children for verb accuracy only. CONCLUSIONS & IMPLICATIONS: This study showed that all four groups of children showed growth over a 6-month period and that bilingual children exposed predominantly to English in the home performed similarly to their monolingual peers in measures of narrative information, sentence length, number of different words and first mentions.

Lack of Fas antagonism by Met in human fatty liver disease.

Hepatocytes in fatty livers are hypersensitive to apoptosis and undergo escalated apoptotic activity via death receptor-mediated pathways, particularly that of Fas-FasL, causing hepatic injury that can eventually proceed to cirrhosis and end-stage liver disease. Here we report that the hepatocyte growth factor receptor, Met, plays an important part in preventing Fas-mediated apoptosis of hepatocytes by sequestering Fas. We also show that Fas antagonism by Met is abrogated in human fatty liver disease (FLD). Through structure-function studies, we found that a YLGA amino-acid motif located near the extracellular N terminus of the Met alpha-subunit is necessary and sufficient to specifically bind the extracellular portion of Fas and to act as a potent FasL antagonist and inhibitor of Fas trimerization. Using mouse models of FLD, we show that synthetic YLGA peptide tempers hepatocyte apoptosis and liver damage and therefore has therapeutic potential.

Mechanism and Effect of HNF4α Decrease in a Rat Model of Cirrhosis and Liver Failure.

BACKGROUND & AIMS: HNF4α, a master regulator of liver development and the mature hepatocyte phenotype, is down-regulated in chronic and inflammatory liver disease. We used contemporary transcriptomics and epigenomics to study the cause and effects of this down-regulation and characterized a multicellular etiology. METHODS: Progressive changes in the rat carbon tetrachloride model were studied by deep RNA sequencing and genome-wide chromatin immunoprecipitation sequencing analysis of transcription factor (TF) binding and chromatin modification. Studies compared decompensated cirrhosis with liver failure after 26 weeks of treatment with earlier compensated cirrhosis and with additional rat models of chronic fibrosis. Finally, to resolve cell-specific responses and intercellular signaling, we compared transcriptomes of liver, nonparenchymal, and inflammatory cells. RESULTS: HNF4α was significantly lower in 26-week cirrhosis, part of a general reduction of TFs that regulate metabolism. Nevertheless, increased binding of HNF4α contributed to strong activation of major phenotypic genes, whereas reduced binding to other genes had a moderate phenotypic effect. Decreased Hnf4a expression was the combined effect of STAT3 and nuclear factor kappa B (NFκB) activation, which similarly reduced expression of other metabolic TFs. STAT/NFκB also induced de novo expression of Osmr by hepatocytes to complement induced expression of Osm by nonparenchymal cells. CONCLUSIONS: Liver decompensation by inflammatory STAT3 and NFκB signaling was not a direct consequence of progressive cirrhosis. Despite significant reduction of Hnf4a expression, residual levels of this abundant TF still stimulated strong new gene expression. Reduction of HNF4α was part of a broad hepatocyte transcriptional response to inflammation.

Damage-associated cellular markers in the clinical and pathogenic profile of vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND: Adenoviral vector-based COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) is rare but carries significant risks of mortality and long-term morbidity. The underlying pathophysiology of severe disease is still not fully understood. The objectives were to explore the pathophysiological profile and examine for clinically informative biomarkers in patients with severe VITT. METHODS: Twenty-two hospitalized patients with VITT, 9 pre- and 21 post-ChAdOx1 vaccine controls, were recruited across England, United Kingdom. Admission blood samples were analyzed for cytokine profiles, cell death markers (lactate dehydrogenase and circulating histones), neutrophil extracellular traps, and coagulation parameters. Tissue specimens from deceased patients were analyzed. RESULTS: There were strong immune responses characterized by significant elevations in proinflammatory cytokines and T helper 1 and 2 cell activation in patients with VITT. Markers of systemic endothelial activation and coagulation activation in both circulation and organ sections were also significantly elevated. About 70% (n = 15/22) of patients met the International Society for Thrombosis and Haemostasis criteria for disseminated intravascular coagulation despite negligible changes in the prothrombin time. The increased neutrophil extracellular trap formation, in conjunction with marked lymphopenia, elevated lactate dehydrogenase, and circulating histone levels, indicates systemic immune cell injury or death. Both lymphopenia and circulating histone levels independently predicted 28-day mortality in patients with VITT. CONCLUSION: The coupling of systemic cell damage and death with strong immune-inflammatory and coagulant responses are pathophysiologically dominant and clinically relevant in severe VITT.

Detecting and Quantifying pADPr In Vivo.

Poly(ADP-ribose) polymerases (PARP) participate in diverse biological processes contributing to cellular homeostasis or exacerbating injury. PARP catalyzes the addition of ADP-ribose molecules (pADPr) to the target proteins, a process termed poly-ADP-ribosylation. Overactivation of PARP - reflected by increased poly-ADP-ribosylation and accumulation of pADPr-modified proteins or free pADPr - contributes to depletion of NAD+ and mitochondrial dysfunction, potentially leading to cell death. Thus, PARP overactivation and increases in free pADPr have been identified as key contributors to the pathobiology of many diseases. In stark contrast, PARP inhibitors are in clinical use in cancer patients where they potentiate cell death induced by chemotherapeutic agents. Accordingly, monitoring PARP-1 activation - responsible for up to 80-90% of cellular pADPr synthesis - by detecting and quantifying pADPr may provide valuable mechanistic insights as well as facilitating therapeutic drug monitoring for PARP inhibitors.Several non-isotopic immunodetection methods for quantifying pADPr are discussed: Western blotting of poly-ADP-ribosylated proteins, cellular localization of pADPr by immunohistochemistry, quantification of pADPr by enzyme-linked immunoassay, and small-scale two-dimensional gel electrophoresis.

Ethnic Differences in the Effects of Five Disciplinary Techniques on Subsequent Externalizing Behavior Problems.

To identify disciplinary alternatives to replace spanking, this study investigated ethnic differences in the associations of five disciplinary techniques with subsequent externalizing behavior problems in a national sample of 7- to 11-year-olds with ANCOVAs and difference-score analyses. Most techniques led to significant reductions in externalizing problems for African-Americans or Hispanics, but only after overcoming known biases in ANCOVA and not for other European-Americans. Privilege removal had the most significantly effective results, followed by grounding. Sending children to their room and spanking significantly reduced externalizing problems only in one or two analyses for African-Americans, whereas removing children's allowance was significantly effective in one overall analysis. Parenting research needs to distinguish between more vs. less effective use of all disciplinary techniques across multiple situational and cultural contexts.

1,4-Dimethyl-piperazin-1-ium 3-hy-droxy-2-naphtho-ate.

The reaction of 1,4-dimethyl-piperazine and 3-hy-droxy-2-naphthoic acid gives the title 1:1 salt, C(6)H(15)N(2) (+)·C(11)H(7)O(3) (-), with a singly protonated piperazinium cation. In the crystal, a single N-H⋯O hydrogen bond links the cations and anions into discrete pairs and the aromatic anions stack along the crystallographic a-axis direction. This results in layers of cations and anions alternating along the crystallographic c-axis direction. An intra-molecular O-H⋯O hydrogen bond is also present.

Assessing for socioeconomic background diversity in behavioral health workforce development programs.

Assessing workforce diversity is an increasing area of evolution. A comprehensive assessment of socioeconomic diversity is important in that it can help identify needs and enable planned inclusion across a range of students. Subsequently, a more comprehensive set of background indicators is needed. The purpose of this brief report is to describe the approach we are using to determine socioeconomic background among individuals participating in a behavioral health workforce program. By using 3 strategies to assess background, we were able to determine that 4 individuals reported being unable to pay for housing, 3 indicated they had sold plasma, and 1 had experienced homelessness since starting graduate school. Our findings provide a starting point for using a comprehensive set of indicators to guide the recruitment and selection process in workforce development programs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Addressing the Challenge of COVID-19: One Health Care Site's Leadership Response to the Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic created an extremely disruptive challenge for health care leaders that required a rapid, dynamic, and innovative response. The purpose of this manuscript is to share the leadership actions and decisions at Mayo Clinic in Florida during the first 6 months of the pandemic (February to July 2020). We note 4 strategies that contributed to an effective response: (1) leverage experience with disaster preparedness and mobilize regional and national networks; (2) use surge models to anticipate and to address supply chain issues as well as practical and financial effects of the pandemic; (3) adapt creatively to establish new safety and procedural protocols in various areas for various populations; and (4) communicate timely information effectively and be the common source of truth. Mayo Clinic in Florida was able to address the surges of patients with COVID-19, to provide ongoing tertiary care, and to restore function within the first 6 months with new, strengthened practices and protocols.

Engaging Community Health Workers and Social Care Staff as Social First Responders during the COVID-19 Crisis.

In this public health practice vignette, we describe an ongoing community and system intervention to identify and address social determinants of health and related needs experienced by ChristianaCare patients and the greater community during the Coronavirus pandemic. This intervention, being conducted by the ChristianaCare Office of Health Equity, in partnership with ChristianaCare's embedded research institute, the Value Institute, and the Community Outreach and Education division of the Helen F. Graham Cancer Center and Research Institute, engages more than 25 community health workers, health Guides, Latinx health promoters and other social care staff as social first responders during the COVID-19 crisis. These experienced front-line social care staff screen patients and community members for social needs; make referrals to agencies and organizations for needed assistance (e.g., food, housing, financial assistance); assess people's understanding of COVID-19 and preventive measures; provide education about COVID-19; and, connect patients and community members to COVID-19 testing and any relevant clinical services. While this ongoing intervention is under evaluation, we share here some preliminary lessons-learned and discuss the critical role that social first responders can play in reducing the growing adverse social and health impacts of COVID-19 across the state of Delaware.

The Met protooncogene is a transcriptional target of NF kappaB: implications for cell survival.

NF kappaB transcription factor regulates gene expression in response to extracellular stimuli such as TNF alpha. The genes regulated by NF kappaB encode for proteins which control cell growth and survival. Met is the tyrosine kinase receptor for hepatocyte growth factor, and it too promotes cell mitogenesis and survival. Previously, we showed that Met gene expression is regulated by TNF alpha. In this report, we identify and characterize a TNF alpha response element in the Met promoter. This element contains tandem C/EBP sites adjacent to an NF kappaB site. Binding of the NF kappaB p65 subunit and C/EBP beta to this element is induced by TNF alpha. To examine the interplay of NF kappaB and Met in vivo, we determined that Met mRNA and protein levels are reduced in the livers of p65-/- mice as compared to controls. In p65-/- mouse embryonic fibroblasts (MEFs), Met induction by TNF alpha is abrogated while Met's basal gene expression is reduced by half as compared to controls. When overexpressed in p65-/- MEFs, Met confers resistance to TNF-alpha-mediated cell death. Conversely, expression of dominant negative Met in wild-type MEFs renders them sensitive to cell death induced by TNF alpha. A similar response following TNF alpha challenge was observed in hepatocytic cells treated with siRNA to knockdown endogenous Met. Together, these results indicate that the Met gene is a direct target of NF kappaB and that Met participates in NF kappaB-mediated cell survival.

Models and determinants of vocabulary growth from kindergarten to adulthood.

BACKGROUND: Increasing evidence suggests that childhood language problems persist into early adulthood. Nevertheless, little is known about how individual and environmental characteristics influence the language growth of individuals identified with speech/language problems. METHOD: Individual growth curve models were utilised to examine how speech/language impairment and environmental variables (socioeconomic status, family separation, and maternal factors) influence vocabulary development from age 5 to 25. Participants were taken from a community sample of children initially diagnosed with speech/language problems at age 5 and their sex- and age-matched controls. RESULTS: The language impaired group had significantly poorer receptive vocabulary than the speech impaired and control groups throughout the 20-year period. Family income was a significant predictor of vocabulary growth when considered separately, but ceased to be a predictor when language impairment status was taken into account. Maternal education and family separation were determinants of vocabulary at age 5, over and above language impairment status. CONCLUSION: Language impairment is a significant risk factor for vocabulary development from childhood to adulthood. Individuals with speech impairment were less impaired on receptive vocabulary than individuals with language impairment. Further investigation into maternal and familial risk factors may provide targets for early intervention with children at risk for language impairment.

Binding of Drug-Activated CAR/Nr1i3 Alters Metabolic Regulation in the Liver.

The constitutive androstane receptor (CAR/Nr1i3) regulates detoxification of drugs and other xenobiotics by the liver. Binding of these compounds, activating ligands, causes CAR to translocate to the nucleus and stimulate genes of detoxification. However, CAR activation also changes metabolism and induces rapid liver growth. To explain this gene regulation, we characterized the genome-wide early binding of CAR; its binding partner, RXRα; and the acetylation that they induced on H4K5. CAR-linked genes showed either stimulation or inhibition and regulated lipid, carbohydrate, and energy metabolism, as well as detoxification. Stimulation of expression increased, but inhibition did not decrease, H4K5Ac. Transcriptional inhibition occurred when CAR bound with HNF4α, PPARα, or FXR on the same enhancers. Functional competition among these bound nuclear receptors normally coordinates transcriptional resources as metabolism shifts. However, binding of drug-activated CAR to the same enhancers adds a new competitor that constitutively alters the normal balance of metabolic gene regulation.

Protein Import into the Endosymbiotic Organelles of Apicomplexan Parasites.

: The organelles of endosymbiotic origin, plastids, and mitochondria, evolved through the serial acquisition of endosymbionts by a host cell. These events were accompanied by gene transfer from the symbionts to the host, resulting in most of the organellar proteins being encoded in the cell nuclear genome and trafficked into the organelle via a series of translocation complexes. Much of what is known about organelle protein translocation mechanisms is based on studies performed in common model organisms; e.g., yeast and humans or Arabidopsis. However, studies performed in divergent organisms are gradually accumulating. These studies provide insights into universally conserved traits, while discovering traits that are specific to organisms or clades. Apicomplexan parasites feature two organelles of endosymbiotic origin: a secondary plastid named the apicoplast and a mitochondrion. In the context of the diseases caused by apicomplexan parasites, the essential roles and divergent features of both organelles make them prime targets for drug discovery. This potential and the amenability of the apicomplexan Toxoplasma gondii to genetic manipulation motivated research about the mechanisms controlling both organelles' biogenesis. Here we provide an overview of what is known about apicomplexan organelle protein import. We focus on work done mainly in T. gondii and provide a comparison to model organisms.

Promoting Regulatory Reform: The African Health Profession Regulatory Collaborative (ARC) for Nursing and Midwifery Year 4 Evaluation.

As countries across sub-Saharan Africa work towards universal health coverage and HIV epidemic control, investments seek to bolster the quality and relevance of the health workforce. The African Health Profession Regulatory Collaborative (ARC) partnered with 17 countries across East, Central, and Southern Africa to ensure nurses and midwives were authorized and equipped to provide essential HIV services to pregnant women and children with HIV. Through ARC, nursing leadership teams representing each country identify a priority regulatory function and develop a proposal to strengthen that regulation over a 1-year period. Each year culminates with a summative congress meeting, involving all ARC countries, where teams present their projects and share lessons learned with their colleagues. During a recent ARC Summative Congress, a group survey was administered to 11 country teams that received ARC Year 4 grants to measure advancements in regulatory function using the five-stage Regulatory Function Framework, and a group questionnaire was administered to 16 country teams to measure improvements in national nursing capacity (February 2011-2016). In ARC Year 4, eight countries implemented continuing professional development projects, Botswana revised their scope of practice, Mozambique piloted a licensing examination to assess HIV-related competencies, and South Africa developed accreditation standards for HIV/tuberculosis specialty nurses. Countries reported improvements in national nursing leaders' teamwork, collaborations with national organizations, regional networking with nursing leaders, and the ability to garner additional resources. ARC provides an effective, collaborative model to rapidly strengthen national regulatory frameworks, which other health professional cadres or regions may consider using to ensure a relevant health workforce, authorized and equipped to meet the emerging demand for health services.

Phonological encoding in the silent speech of persons who stutter.

UNLABELLED: The purpose of the present study was to investigate the role of phonological encoding in the silent speech of persons who stutter (PWS) and persons who do not stutter (PNS). Participants were 10 PWS (M=30.4 years, S.D.=7.8), matched in age, gender, and handedness with 11 PNS (M=30.1 years, S.D.=7.8). Each participant performed five tasks: a familiarization task, an overt picture naming task, a task of self-monitoring target phonemes during concurrent silent picture naming, a task of monitoring target pure tones in aurally presented tonal sequences, and a simple motor task requiring finger button clicks in response to an auditory tone. Results indicated that PWS were significantly slower in phoneme monitoring compared to PNS. No significant between-group differences were present for response speed during the auditory monitoring, picture naming or simple motor tasks, nor did the two groups differ for percent errors in any of the experimental tasks. The findings were interpreted to suggest a specific deficiency at the level of phonological monitoring, rather than a general monitoring, reaction time or auditory monitoring deficit in PWS. EDUCATIONAL OBJECTIVES: As a result of this activity, the participant should: (1) identify and assess the literature on phonological encoding skills in PWS, (2) enumerate and evaluate some major psycholinguistic theories of stuttering, and (3) describe the mechanism by which defective phonological encoding can disrupt fluent speech production.

Getting started in evidence-based practice for childhood speech-language disorders.

PURPOSE: Evidence-based practice (EBP) entails a critical mindset and rigorous methods that foster the judicious integration of scientific evidence into clinical decision making. The purpose of this tutorial is to present strategies, resources, and examples to help speech-language pathologists get started in EBP for childhood speech and language disorders. METHOD: The tutorial begins with an overview of key principles of EBP, including potential benefits and challenges, and other initial considerations. Five recommended steps for implementing EBP are then presented: posing a question, locating the evidence, appraising the evidence, making and implementing clinical decisions, and evaluating those decisions. Included is a compilation of synthesized evidence resources, such as systematic reviews/meta-analyses and EBP guidelines. Finally, illustrative examples are provided to assist practitioners with integrating research evidence into clinical decision making in childhood speech-language disorders. CONCLUSIONS: Speech-language pathologists who work with children are encouraged to adopt EBP for clinical decision making.

Regulatory Advances in 11 Sub-Saharan Countries in Year 3 of the African Health Profession Regulatory Collaborative for Nurses and Midwives (ARC).

Sub-Saharan Africa carries the greatest burden of the HIV pandemic. Enhancing the supply and use of human resources through policy and regulatory reform is a key action needed to improve the quality of HIV services in this region. In year 3 of the African Health Profession Regulatory Collaborative for Nurses and Midwives (ARC), a President's Emergency Plan for AIDS Relief initiative, 11 country teams of nursing and midwifery leaders ("Quads") received small grants to carry out regulatory improvement projects. Four countries advanced a full stage on the Regulatory Function Framework (RFF), a staged capability maturity model used to evaluate progress in key regulatory functions. While the remaining countries did not advance a full stage on the RFF, important gains were noted. The year-3 evaluation highlighted limitations of the ARC evaluation strategy to capture nuanced progress and provided insight into how the RFF might be adapted for future use.

Early language impairment and young adult delinquent and aggressive behavior.

Clinic and forensic studies have reported high rates of language impairments in conduct disordered and incarcerated youth. In community samples followed to early adolescence, speech and language impairments have been linked to attention deficits and internalizing problems, rather than conduct problems, delinquency, or aggression. This study examines the young adult antisocial outcomes of speech or language impaired children. Language impaired boys had higher levels of parent-rated delinquency symptoms by age 19 than boys without language impairment, controlled for verbal IQ and for demographic and family variables. Language impaired boys did not differ from controls in self-reported delinquency or aggression symptoms on a standardized checklist; however, language impaired boys reported higher rates of arrests and convictions than controls. Language impairment was not related to aggression or delinquency in girls. We examine alternate models of the interrelationships between language, academics, and behavior, at ages 5, 12, and 19.