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Natural resources, especially minerals from the earth, are to be protected by humanity. The church, which acts as leaven in the world is called to rise and address the unfriendly mining activities called mining-induced displacement and resettlement (MIDR). The general theory of interpretation of creation account calls for human stewardship in the world. Humans must view themselves as partners with God in preserving and sustaining the cosmos. The communities had suffered negative socio-economic imbalances. The ekklesia in this cosmic chaos is called upon to fulfil four major functions, namely identity, integration, policy, and management as a way of intervention in communities that are victims of these mining activities. This response, ecclesiology in context, is the combination of theological and social-scientific approaches to the development of practical models and strategies for the church’s interaction with modern society and its challenges.

The scope of this article is to expand the shepherd model of leadership functions as portrayed by the shepherd metaphor. The identification and the biblical usage of the shepherd and the sheep is explored, with special focus on the role of the shepherd. This role is identified as that of caring, courage, and guidance. The caring function includes activities such as restoration, feeding, watering, grooming, shearing, delivering lambs, leading, and protection. The function of courage focuses on activities of assuming responsibility, serving and participating in change. The function of guidance gives a special highlight on hodegos [leader or guide] – to lead or to guide in regard to a decision or future course of action. This is where the leadership training is based. The conclusion is the call for leaders in the ecclesiastical community to pursue the shepherd-leader model for the advance and the effectiveness of the mission Dei [mission of God] in the world.

This study, conducted in Bloemfontein, found wide discrepancies between the prescriptions of the Basic Conditions of Employment Act and the actual working conditions of waiters. In order to make waiters' situation compliant with the law, several changes will have to be made. However, it was also found that not all changes would necessarily benefit the waiters. Policy makers should therefore be cautious in addressing these discrepancies and making a sectoral determination for waiters.

Human T-cell leukemia virus type 1 (HTLV-1) infects CD4+ T-cells through close cell–cell contacts. The viral Tax-1 (Tax) protein regulates transcription by transactivating the HTLV-1 U3R promoter in the 5′ long terminal repeat of the integrated provirus. Here, we generated a clonal Tax-responsive T-cell line to track HTLV-1 infection at the single-cell level using flow cytometry, bypassing intracellular viral protein staining. Jurkat T-cells stably transduced with the SMPU vector carrying green fluorescent protein (GFP) under control of 18 × 21 bp Tax-responsive element repeats of the U3R were evaluated. Among 40 clones analyzed for Tax responsiveness, the top two were characterized. Upon overexpression of Tax, over 40% of the cells showed GFP positivity, and approximately 90% of the Tax-positive cells were GFP-positive, indicating efficient reporter activity. However, with CREB-deficient Tax mutant M47, both total GFP-positive cell counts and those within the Tax-positive group significantly decreased. Co-culture with chronically HTLV-1-infected MT-2 or C91-PL cells led to an average of 0.9% or 2.4% GFP-positive cells, respectively, confirming the suitability to monitor HTLV-1 transmission and that HTLV-1 infection is very low. Thus, the novel Tax-responsive reporter T-cell line is a suitable tool to monitor infection of HTLV-1 on the single-cell level.

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The transmission of viruses from one host to another typically occurs through horizontal or vertical pathways. The horizontal pathways include transmission amongst individuals, usually through bodily fluids or excretions, while vertical transmission transpires from mother to their offspring, either during pregnancy, childbirth, or breastfeeding. While there are more than 200 human pathogenic viruses to date, only a small number of them are known to be transmitted via breast milk, including cytomegalovirus (CMV), human immunodeficiency virus type 1 (HIV-1), and human T cell lymphotropic virus type 1 (HTLV-1), the latter two belonging to the family Retroviridae. Breast milk transmission is a common characteristic among mammalian retroviruses, but there is a lack of reports summarizing our knowledge regarding this route of transmission of mammalian retroviruses. Here, we provide an overview of the transmission of mammalian exogenous retroviruses with a focus on Orthoretrovirinae, and we highlight whether they have been described or suspected to be transmitted through breast milk, covering various species. We also elaborate on the production and composition of breast milk and discuss potential entry sites of exogenous mammalian retroviruses during oral transmission.

Abstract Background Human T-cell leukemia virus type 1 (HTLV-1) infects primarily CD4+ T-lymphocytes and evoques severe diseases, predominantly Adult T-Cell Leukemia/ Lymphoma (ATL/L) and HTLV-1-associated Myelopathy/ Tropical Spastic Paraparesis (HAM/TSP). The viral transactivator of the pX region (Tax) is important for initiating malignant transformation, and deregulation of the major signaling pathway nuclear factor of kappa B (NF-κB) by Tax represents a hallmark of HTLV-1 driven cancer. Results Here we found that Tax mutants which are defective in NF-κB signaling showed diminished protein expression levels compared to Tax wildtype in T-cells, whereas Tax transcript levels were comparable. Strikingly, constant activation of NF-κB signaling by the constitutive active mutant of inhibitor of kappa B kinase (IKK2, IKK-β), IKK2-EE, rescued protein expression of the NF-κB defective Tax mutants M22 and K1-10R and even increased protein levels of Tax wildtype in various T-cell lines while Tax transcript levels were only slightly affected. Using several Tax expression constructs, an increase of Tax protein occurred independent of Tax transcripts and independent of the promoter used. Further, Tax and M22 protein expression were strongly enhanced by 12-O-Tetradecanoylphorbol-13-Acetate [TPA; Phorbol 12-myristate 13-acetate (PMA)]/ ionomycin, inducers of NF-κB and cytokine signaling, but not by tumor necrosis factor alpha (TNF-α). On the other hand, co-expression of Tax with a dominant negative inhibitor of κB, IκBα-DN, or specific inhibition of IKK2 by the compound ACHP, led to a vast decrease in Tax protein levels to some extent independent of Tax transcripts in transiently transfected and Tax-transformed T-cells. Cycloheximide chase experiments revealed that co-expression of IKK2-EE prolongs the half-life of M22, and constant repression of NF-κB signaling by IκBα-DN strongly reduces protein stability of Tax wildtype suggesting that NF-κB activity is required for Tax protein stability. Finally, protein expression of Tax and M22 could be recovered by NH4Cl and PYR-41, inhibitors of the lysosome and the ubiquitin-activating enzyme E1, respectively. Conclusions Together, these findings suggest that Tax’s capability to induce NF-κB is critical for protein expression and stabilization of Tax itself. Overall, identification of this novel positive feedback loop between Tax and NF-κB in T-cells improves our understanding of Tax-driven transformation.

Background: The Serious Illness Care Program (SICP), developed in 2011 by Ariadne Labs, restructures care so that knowing and then honoring patients' wishes becomes part of routine care. Objectives: 1) summarize patient perceptions of use of the Serious Illness Conversation Guide (SICG) components, 2) assess whether a serious illness conversation was documented in the electronic health record (EHR) and identify the SICG components that were included, 3) summarize clinician perceptions of use of the SICG components, and 4) assess the association of documented SICG components with the patient's perception of the SICG discussion. Methods: Clinicians at three family medicine offices were trained in serious illness conversations using the SICG. They documented their serious illness conversations in the medical record. Retrospective chart review for SICG components was conducted for patients. Patients and clinicians completed questionnaires about their experience with the SICG. Statistical analysis included the Pearson chi-square test for categorical variables and Cohen's kappa to determine agreement between clinician documentation and patient perception. Results: Eighty-nine patients consented and completed their baseline questionnaire. Mean age of the 89 patients was 72 years and 65 (73%) were female. Thirty (34%) medical records had one or more SICG components documented. Seventy-nine (89%) patients reported at least one individual component of the SICG being discussed. Clinicians reported they engaged in asking patients what is important to them at a mean of 5.9, with 7 being "all the time". There was slight agreement (kappa = .19) for patient perception and clinician documentation of discussing patient goals, but no agreement for any of the other SICG components. Conclusion: Even among trained clinicians, only one-third of patients had documentation of at least one SICG component. Only slight agreement was found between clinician documentation of SICG in the medical record and patient perception of SICG discussion.

Autosomal dominant (AD) NFKB1 deficiency is thought to be the most common genetic etiology of common variable immunodeficiency (CVID). However, the causal link between NFKB1 variants and CVID has not been demonstrated experimentally and genetically, and there has been insufficient biochemical characterization and enrichment analysis. We show that the cotransfection of NFKB1-deficient HEK293T cells (lacking both p105 and its cleaved form p50) with a κB reporter, NFKB1/p105, and a homodimerization-defective RELA/p65 mutant results in p50:p65 heterodimer-dependent and p65:p65 homodimer-independent transcriptional activation. We found that 59 of the 90 variants in patients with CVID or related conditions were loss of function or hypomorphic. By contrast, 258 of 260 variants in the general population or patients with unrelated conditions were neutral. None of the deleterious variants displayed negative dominance. The enrichment in deleterious NFKB1 variants of patients with CVID was selective and highly significant (P = 2.78 × 10-15). NFKB1 variants disrupting NFKB1/p50 transcriptional activity thus underlie AD CVID by haploinsufficiency, whereas neutral variants in this assay should not be considered causal., Competing Interests: Disclosures:   S.J. Pelham became employed at Takeda UK Ltd. after contributing to this work. B. Grimbacher reported grants from BMBF, DFG, several pharmaceutical companies, and foundations, and personal fees from several pharmaceutical companies outside the submitted work. No other disclosures were reported., (© 2021 Li et al.)

Introduction: All physicians must learn comprehensive patient care delivery within the electronic health record (EHR). No studies have considered EHR communication training with an emphasis on clinical efficiency. This curriculum provides a method of teaching clinic efficiency while practicing effective patient communication in any EHR clinical situation. The target audience is resident physicians, fellow physicians, faculty physicians, and physician extenders practicing in a primary care setting where the EHR is present., Methods: This curriculum of four separate workshops provides a structured EHR approach while addressing communication strategies for preclinical preparation, rapport building, encounter initiation, agenda setting, and visit closure. The curriculum contains interactive presentations, tools, and an evaluation survey. Presenting efficiency issues with the EHR using the ATTEND mnemonic and agenda setting allows documentation while practicing communication techniques that maximize efficiency., Results: Postworkshop surveys revealed that participants felt the workshops were helpful (84%). One measurement of efficiency revealed improvement through decreased number of days to note completion after workshop participation. At the Program Directors Workshop, curriculum value was demonstrated by high attendance, with 94% feeling the workshops provided easily utilizable strategies., Discussion: The curriculum utilized only the EPIC EHR but would be generalizable. Future directions could include measurement of effective communication and visit efficiency through direct observation and expanded EHR timing data., (© 2020 Skelly et al.)

Monitoring of transcranial electrical motor evoked potentials (tcMEP) during carotid endarterectomy (CEA) has been shown to effectively detect intraoperative cerebral ischemia. The unique purpose of this study was to evaluate changes of MEP amplitude (AMP), area under the curve (AUC) and signal morphology (MOR) as additional MEP warning criteria for clamping-associated ischemia during CEA. Therefore, the primary outcome was the number of MEP alerts (AMP, AUC and MOR) in the patients without postoperative motor deficit (false positives). We retrospectively reviewed data from 571 patients who received CEA under general anesthesia. Monitoring of somatosensory evoked potentials (SSEP) and tcMEP was performed in all cases (all-or-none MEP warning criteria). The percentages of false positives (primary parameter) of AMP, AUC and MOR were evaluated according to the postoperative motor outcome. In the cohort of 562 patients, we found significant SSEP/MEP changes in 56 patients (9.96%). In 44 cases (7.83%) a shunt was inserted. Nine patients (1.57%) were excluded due to MEP recording failure. False positives were registered for AMP, AUC and MOR changes in 121 (24.01%), 148 (29.36%) and 165 (32.74%) patients, respectively. In combination of AMP/AUC and AMP/AUC/MOR false positives were found in 9.52% and 9.33% of the patients. This study is the first to evaluate the correctness of the MEP warning criteria AMP, AUC and MOR with regard to false positive monitoring results in the context of CEA. All additional MEP warning criteria investigated produced an unacceptably high number of false positives and therefore may not be useful in carotid surgery for adequate detection of clamping-associated ischemia.

Background: Changes of cerebral diffusivity detected by magnetic resonance imaging (MRI) have been reported in epilepsy. Diffusion weighted imaging (DWI) detects changes in the distribution of water molecules by measuring the apparent diffusion coefficient (ADC) and is mainly used in the diagnosis of ischemic stroke. DWI changes in epilepsy were reported in status epilepticus (SE) or series of seizures. It remains unclear whether this phenomenon also occurs after single seizures. Accordingly, possible pathomechanisms have only been discussed on the presumed basis of ongoing epileptic brain activity. Methods: In this retrospective study, we systematically analyzed DWI alterations related to epileptic seizures in 454 patients who received MRI scanning within the first 24 h after seizure onset. Results: DWI restrictions not classified as ischemic stroke were observed in 18 patients (4%). We found DWI restrictions in 19% of patients with SE/seizure series and in 3% of patients after single focal and 2.5% after single generalized seizures. 17 patients with DWI alterations were diagnosed with a structural epilepsy. DWI signal decreased in the majority of patients within the first days and could not be detected in follow-up imaging >3 months. In all patients except one, DWI alterations were detected in the same hemisphere as the lesion. In the case of seizure series or SE, DWI restrictions mostly presented with a typical "garland-like" pattern alongside the cortical band or on the border of a defined lesion, while in isolated seizures, the restrictions were often rather subtle and small. Discussion: We show that DWI restrictions can be observed in patients after single epileptic seizures. As the vast majority of these patients was diagnosed with an epilepsy due to structural cerebral pathology, DWI restriction may reflect a higher vulnerability in these regions. This might also explain the fact that diffusivity changes were observed after single focal seizures as well as after multiple seizures or SE. The occurence itself on one side as well as the spatial pattern of this phenomenon on the other may thus not only be related to the duration of ictal activity, but to structural pathology.

In this study we used a genetic extracellular matrix (ECM) disease to identify mechanisms associated with aggressive behavior of cutaneous squamous cell carcinoma (cSCC). cSCC is one of the most common malignancies and usually has a good prognosis. However, some cSCCs recur or metastasize and cause significant morbidity and mortality. Known factors that are associated with aggressiveness of cSCCs include tumor grading, size, localization and microinvasive behavior. To investigate molecular mechanisms that influence biologic behavior we used global proteomic and histologic analyses of formalin-fixed paraffin-embedded tissue of primary human cSCCs. We compared three groups: non-recurring, non-metastasizing low-risk sporadic cSCCs; metastasizing sporadic cSCCs; and cSCCs from patients with recessive dystrophic epidermolysis bullosa (RDEB). RDEB is a genetic skin blistering and ECM disease caused by collagen VII deficiency. Patients commonly suffer from high-risk early onset cSCCs that frequently metastasize. The results indicate that different processes are associated with formation of RDEB cSCCs compared to sporadic cSCCs. Sporadic cSCCs show signs of UV damage, whereas RDEB cSCCs have higher mutational rates and display tissue damage, inflammation and subsequent remodeling of the dermal ECM as tumor initiating factors. Interestingly the two high-risk groups - high-risk metastasizing sporadic cSCCs and RDEB cSCCs - are both associated with tissue damage and ECM remodeling in gene-ontology enrichment and Search Tool for the Retrieval of Interacting Genes/Proteins analyses. In situ histologic analyses validate these results. The high-risk cSCCs also show signatures of enhanced bacterial challenge. Histologic analyses confirm correlation of bacterial colonization with worse prognosis. Collectively, this unbiased study - performed directly on human patient material - reveals that common microenvironmental alterations linked to ECM remodeling and increased bacterial challenges are denominators of high-risk cSCCs. The proteins identified here could serve as potential diagnostic markers and therapeutic targets in high-risk cSCCs., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The enzyme indoleamine 2,3-dioxygenase (IDO) is emerging as a facilitator of cancer development through its effects on cancer-associated inflammation. Recent studies report a significant improvement of the response rates in melanoma patients to PD-1 antibodies when IDO inhibitors were added to the regimen. Data on IDO expression in primary human melanomas are, however, incomplete and conflicting. Here, we show that the level of IDO expression in primary human melanoma cells significantly correlates with Breslow thickness (P = 0.003), the presence of tumor-infiltrating lymphocytes (P = 0.029), and the intensity of the peritumoral inflammatory infiltrate (P = 0.001). The expression of IDO in melanoma cells predicted independently of Breslow thickness and tumor stage (P = 0.04). We further show that CD11c + dendritic cells and CD68 + macrophages in the microenvironment of melanomas express IDO. The level of IDO expression in antigen-presenting cells correlated positively to peritumoral inflammation (P = 0.001) but not to tumor-infiltrating lymphocytes. Significant negative correlation with progression-free survival was found for patients for whom antigen-presenting cells were very strongly IDO positive. These results suggest that IDO induction within melanoma cells may directly reflect tumor progression, whereas IDO in antigen-presenting cells may determine immune surveillance with impact on local and systemic tolerance., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Women living with HIV/AIDS who drink alcohol are at increased risk for adverse health outcomes, but there is little evidence on best methods for reducing alcohol consumption in this population. We conducted a pilot study to determine the acceptability and feasibility of conducting a larger randomized clinical trial of naltrexone vs. placebo to reduce alcohol consumption in women living with HIV/AIDS., Methods: We designed the trial with input from community and scientific review. Women with HIV who reported current hazardous drinking (>7 drinks/week or ≥4 drinks per occasion) were randomly assigned to daily oral naltrexone (50mg) or placebo for 4months. We evaluated willingness to enroll, adherence to study medication, treatment side effects, and drinking and HIV-related outcomes., Results: From 2010 to 2012, 17 women enrolled (mean age 49years, 94% African American). Study participation was higher among women recruited from an existing HIV cohort study compared to women recruited from an outpatient HIV clinic. Participants took 73% of their study medication; 82% completed the final assessment (7-months). Among all participants, mean alcohol consumption declined substantially from baseline to month 4 (39.2 vs. 12.8 drinks/week, p<0.01) with continued reduction maintained at 7-months. Drinking reductions were similar in both naltrexone and placebo groups., Conclusions: A pharmacologic alcohol intervention was acceptable and feasible in women with HIV, with reduced alcohol consumption noted in women assigned to both treatment and placebo groups. However, several recruitment challenges were identified that should be addressed to enhance recruitment in future alcohol treatment trials., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This study shows the start-up and operation of a full-scale sequencing batch reactor (SBR) with a volume of 550 m³ for deammonification of reject water from sludge dewatering over the first 650 days of operation. The SBR was operated with discontinuous aeration and achieved an optimum of around 85% of ammonium removal at a load of 0.17 kg m⁻³ d⁻¹. The application of batch tests for the activity measurement of aerobic ammonium and nitrite oxidizing bacteria and anaerobic ammonium oxidizing bacteria were proven to support the identification of setbacks in reactor operation. Furthermore, the calculation of the oxygen uptake rates from online oxygen measurements helped to explain the overall reactor performance. The aeration regime is a key parameter for stable operation of such an SBR for deammonification. At aeration/non-aeration time ranges from 6-9 min, the best results with respect to turnover rates and low nitrate production were achieved. Compared with the nitrification/denitrification SBR operated in parallel with methanol as the carbon source, a significant reduction in costs for energy and chemicals was achieved. The costs for maintenance slightly increased.

This article aims to examine the epidemiological transition in Nauru through analysis of available mortality data. Mortality data from death certificates and published material were used to construct life tables and calculate age-standardized mortality rates (from 1960) with 95% confidence intervals. Proportional mortality was calculated from 1947. Female life expectancy (LE) varied from 57 to 61 years with no significant trend. Age-standardized mortality for males (15-64 years) doubled from 1960-1970 to 1976-1981 and then decreased to 1986-1992, with LE fluctuating since then from 49 to 54 years. Proportional mortality from cardiovascular disease and diabetes increased substantially, reaching more than 30%. Nauru demonstrates a very long period of stagnation in life expectancy in both males and females as a consequence of the epidemiological transition, with major chronic disease mortality in adults showing no sustained downward trends over 40 years. Potential overinterpretation of trends from previous data due to lack of confidence intervals was highlighted.

The discovery of copy number variations (CNV) in the human genome opened new perspectives in the study of the genetic causes of inherited disorders and the etiology of common diseases. Differently patterned instances of somatic mosaicism in CNV regions have been shown to be present in monozygotic twins and throughout different tissues within an individual. A single-cell-level investigation of CNV in different human cell types led us to uncover mitotically derived genomic mosaicism, which is stable in different cell types of one individual. A unique study of immortalized B-lymphoblastoid cell lines obtained with 20 year interval from the same two subjects shows that mitotic changes in CNV regions may happen early during embryonic development and seem to occur only once, as levels of mosaicism remained stable. This finding has the potential to change our concept of dynamic human genome variation. We propose that further genomic studies should focus on the single-cell level, to understand better the etiology and physiology of aging and diseases mediated by somatic variations.

Objective: To assess the clinical capacity of a bioabsorbable root analog to close oroantral perforations after extraction., Study Design: In this prospective case-cohort study, 20 consecutive patients with oroantral communications greater than 2 mm were treated with a bioabsorbable root analog (RootReplica). Patients were followed up clinically and radiographically for 3 months to monitor the healing process., Results: Root replicas could be placed in 14 patients, whereas 6 patients required the socket to be covered with a buccal sliding flap. In the latter cases, fragmentary roots or overly large defects prohibited replica fabrication or accurate fitting of the analog, respectively. Healing was uneventful in all patients, and epistaxis, swelling, or pain was observed only in patients treated with flaps., Conclusions: The method described is a valuable alternative method with which to close oroantral communications but cannot be performed in all patients because of technical limitations.

Osteopontin (OPN) has been shown to have T helper 1 (Th1) cytokine functions in cell-mediated immunity. Deficiency of OPN is linked to a reduced Th1 immune response in autoimmunity, infectious disease, and delayed-type allergy. Dendritic cells (DCs) are central for the induction of T-cell-mediated immunity, when initially flexible DCs are instructed by priming signals and tissue-derived factors to adopt Th1, Th2, or regulatory T-cell-inducing phenotypes. Although OPN influences the cytokine secretion of T cells and macrophages, its effects on DC polarization remain an important missing link in the understanding of OPN functions in Th1 immunity. Here we demonstrate that OPN promotes the emigration of human DCs from the epidermis and functionally activates myeloid-type DCs, augmenting their expression of HLA-DR, costimulatory, and adhesion molecules. OPN induces their Th1-promoting tumor necrosis factor alpha (TNF-alpha) and interleukin-12 (IL-12) secretion, and enhances their allostimulatory capacity. In mixed lymphocyte reactions (MLRs), OPN stimulates IL-12 secretion by DCs, inducing elevated interferon-gamma (IFN-gamma) production by T cells. Naive Th cells stimulated by OPN-activated DCs show a Th1-polarized cytokine production. Our findings identify OPN as an important tissue-derived factor that DCs encounter when traveling from peripheral sites of activation to secondary lymphatic organs, which induces DC maturation toward a Th1-promoting phenotype.