Sex chromosome positions in human interphase nuclei as studied by in situ hybridization with chromosome specific DNA probes

Two cloned repetitive DNA probes, pXBR and CY1, which bind preferentially to specific regions of the human X and Y chromosome, respectively, were used to study the distribution of the sex chromosomes in human lymphocyte nuclei by in situ hybridization experiments. Our data indicate a large variability of the distances between the sex chromosomes in male and female interphase nuclei. However, the mean distance observed between the X and Y chromosome was significantly smaller than the mean distance observed between the two X-chromosomes. The distribution of distances determined experimentally is compared with three model distributions of distances, and the question of a non-random distribution of sex chromosomes is discussed. Mathematical details of these model distributions are provided in an Appendix to this paper. In the case of a human translocation chromosome (XqterXp22.2::Yq11Y qter) contained in the Chinese hamster x human hybrid cell line 445 x 393, the binding sites of pXBR and CY1 were found close to each other in most interphase nuclei. These data demonstrate the potential use of chromosome-specific repetitive DNA probes to study the problem of interphase chromosome topography

Evaluation of Interventions in Blended Learning Using a Communication Skills Serious Game

Serious games often employ a scripted dialogue for player interaction with a virtual character. In our serious game Communicate, a domain expert develops a structured, scripted scenario as a sequence of potential interactions in an authoring tool. A player is often a student learning communication skills and a virtual character represents a person that a student talks to. In the original version of Communicate, a player `converses' with a virtual character by clicking on one of the multiple statement options. Since 2018, we perform blended learning sessions for final year computer science students using Communicate. Our goal is to improve these sessions and in this paper, we apply the action research method over three semesters to iteratively improve these blended learning sessions. In the first semester, our baseline, we conduct sessions where students play a scenario in multiple choice format. In the second semester, we enhance Communicate by enabling a student to enter open text input in an improved scenario. In the third semester, we enhance a session by incorporating peer teaching. Students fill in an evaluation survey after a session and we compare the evaluation of students from the three semesters. Results show that student ratings are significantly higher in sessions incorporating peer teaching compared to the baseline

Sources of Community Health Worker Motivation: A Qualitative Study in Morogoro Region, Tanzania.

There is a renewed interest in community health workers (CHWs) in Tanzania, but also a concern that low motivation of CHWs may decrease the benefits of investments in CHW programs. This study aimed to explore sources of CHW motivation to inform programs in Tanzania and similar contexts. We conducted semi-structured interviews with 20 CHWs in Morogoro Region, Tanzania. Interviews were digitally recorded, transcribed, and coded prior to translation and thematic analysis. The authors then conducted a literature review on CHW motivation and a framework that aligned with our findings was modified to guide the presentation of results. Sources of CHW motivation were identified at the individual, family, community, and organizational levels. At the individual level, CHWs are predisposed to volunteer work and apply knowledge gained to their own problems and those of their families and communities. Families and communities supplement other sources of motivation by providing moral, financial, and material support, including service fees, supplies, money for transportation, and help with farm work and CHW tasks. Resistance to CHW work exhibited by families and community members is limited. The organizational level (the government and its development partners) provides motivation in the form of stipends, potential employment, materials, training, and supervision, but inadequate remuneration and supplies discourage CHWs. Supervision can also be dis-incentivizing if perceived as a sign of poor performance. Tanzanian CHWs who work despite not receiving a salary have an intrinsic desire to volunteer, and their motivation often derives from support received from their families when other sources of motivation are insufficient. Policy-makers and program managers should consider the burden that a lack of remuneration imposes on the families of CHWs. In addition, CHWs' intrinsic desire to volunteer does not preclude a desire for external rewards. Rather, adequate and formal financial incentives and in-kind alternatives would allow already-motivated CHWs to increase their commitment to their work

To what extent do site-based training, mentoring, and operational research improve district health system management and leadership in low- and middle-income countries: a systematic review protocol

District health managers play a key role in the effectiveness of decentralized health systems in low- and middle-income countries. Inadequate management and leadership skills often hamper their ability to improve quality of care and effectiveness of health service delivery. Nevertheless, significant investments have been made in capacity-building programmes based on site-based training, mentoring, and operational research. This systematic review aims to review the effectiveness of site-based training, mentoring, and operational research (or action research) on the improvement of district health system management and leadership. Our secondary objectives are to assess whether variations in composition or intensity of the intervention influence its effectiveness and to identify enabling and constraining contexts and underlying mechanisms

Full-length structural model of RET3 and SEC21 in COPI: identification of binding sites on the appendage for accessory protein recruitment motifs

COPI, a 600 kD heptameric complex (consisting of subunits α, β, γ, δ, ε, ζ, and β′) “coatomer,” assembles non-clathrin-coated vesicles and is responsible for intra-Golgi and Golgi-to-ER protein trafficking. Here, we report the three-dimensional structures of the entire sequences of yeast Sec21 (γ-COPI mammalian ortholog), yeast Ret3 (ζ-COPI mammalian ortholog), and the results of successive molecular dynamics investigations of the subunits and assembly based on a protein–protein docking experiment. The three-dimensional structures of the subunits in their complexes indicate the residues of the two subunits that impact on assembly, the conformations of Ret3 and Sec21, and their binding orientations in the complexed state. The structure of the appendage domain of Sec21, with its two subdomains—the platform and the β-sandwich, was investigated to explore its capacity to bind to accessory protein recruitment motifs. Our study shows that a binding site on the platform is capable of binding the Eps15 DPF and epsin DPW2 peptides, whereas the second site on the platform and the site on the β-sandwich subdomain were found to selectively bind to the amphiphysin FXDXF and epsin DPW1 peptides, respectively. Identifying the regions of both the platform and sandwich subdomains involved in binding each peptide motif clarifies the mechanism through which the appendage domain of Sec21 engages with the accessory proteins during the trafficking process of non-clathrin-coated vesicles

S-100B as an extra selection tool for FDG PET/CT scanning in follow-up of AJCC stage III melanoma patients

Background and Objectives This current study assessed the value of S-100B measurement to guide fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scanning for detecting recurrent disease in stage III melanoma patients. Methods This study included 100 stage III melanoma patients in follow-up after curative lymph node dissection. Follow-up visits included physical examination and S-100B monitoring. FDG PET/CT scanning was indicated by clinical symptoms and/or elevated S-100B. Results Of 100 patients, 13 (13%) had elevated S-100B without clinical symptoms, of whom 7 (54%) showed disease evidence upon FDG PET/CT scanning. Twenty-six patients (26%) had clinical symptoms with normal S-100B and FDG PET/CT revealed metastasis in 20 (77%). Three patients had clinical symptoms and elevated S-100B, and FDG PET/CT revealed metastasis in all three (100%). Overall, FDG PET/CT scanning revealed metastasis in 30 of the 42 patients (71.4%). For seven recurrences, elevated S-100B prompted early detection of asymptomatic disease; 10% of all asymptomatic patients in follow-up, 23% of all patients with recurrent disease. Conclusion S-100B cannot exclude recurrent disease during follow-up of stage III melanoma. However, adding S-100B measurement to standard clinical assessment can guide FDG PET/CT scanning for detecting recurrent melanoma

SUPPORT Tools for evidence-informed health Policymaking (STP) 15: Engaging the public in evidence-informed policymaking

This article is part of a series written for people responsible for making decisions about health policies and programmes and for those who support these decision makers

The Braincase of the Basal Sauropod Dinosaur Spinophorosaurus and 3D Reconstructions of the Cranial Endocast and Inner Ear

Background: Sauropod dinosaurs were the largest animals ever to walk on land, and, as a result, the evolution of their remarkable adaptations has been of great interest. The braincase is of particular interest because it houses the brain and inner ear. However, only a few studies of these structures in sauropods are available to date. Because of the phylogenetic position of Spinophorosaurus nigerensis as a basal eusauropod, the braincase has the potential to provide key evidence on the evolutionary transition relative to other dinosaurs. Methodology/Principal Findings: The only known braincase of Spinophorosaurus (‘Argiles de l'Irhazer’, Irhazer Group; Agadez region, Niger) differs significantly from those of the Jurassic sauropods examined, except potentially for Atlasaurus imelakei (Tilougguit Formation, Morocco). The basisphenoids of Spinophorosaurus and Atlasaurus bear basipterygoid processes that are comparable in being directed strongly caudally. The Spinophorosaurus specimen was CT scanned, and 3D renderings of the cranial endocast and inner-ear system were generated. The endocast resembles that of most other sauropods in having well-marked pontine and cerebral flexures, a large and oblong pituitary fossa, and in having the brain structure obscured by the former existence of relatively thick meninges and dural venous sinuses. The labyrinth is characterized by long and proportionally slender semicircular canals. This condition recalls, in particular, that of the basal non-sauropod sauropodomorph Massospondylus and the basal titanosauriform Giraffatitan. Conclusions/Significance: Spinophorosaurus has a moderately derived paleoneuroanatomical pattern. In contrast to what might be expected early within a lineage leading to plant-eating graviportal quadrupeds, Spinophorosaurus and other (but not all) sauropodomorphs show no reduction of the vestibular apparatus of the inner ear. This character-state is possibly a primitive retention in Spinophorosaurus, but due the scarcity of data it remains unclear whether it is also the case in the various later sauropods in which it is present or whether it has developed homoplastically in these taxa. Any interpretations remain tentative pending the more comprehensive quantitative analysis underway, but the size and morphology of the labyrinth of sauropodomorphs may be related to neck length and mobility, among other factors.The sojourns of Dr. Knoll in the Museum für Naturkunde (Berlin) were partly funded by the Alexander von Humboldt Foundation through a sponsorship of renewed research stay in Germany and by the European Community Research Infrastructure Action under the FP7 “Capacities” Program through a Synthesys grant (http://www.synthesys.info/). Dr. Knoll is currently supported by the Ramón y Cajal Program. This is a contribution to the research project CGL2009-12143, from the Ministerio de Ciencia e Innovación (Madrid), conducted by Dr. Knoll (PI), Dr. Witmer, and Dr. Schwarz-Wings. Dr. Witmer and Dr. Ridgely acknowledge funding support from the United States National Science Foundation (IBN-9601174, IBN-0343744, IOB-0517257) and the Ohio University Heritage College of Osteopathic Medicine. The Ohio Supercomputing Center also provided support.Peer reviewe

A realist synthesis of randomised control trials involving use of community health workers for delivering child health interventions in low and middle income countries

<p>Abstract</p> <p>Background</p> <p>A key constraint to saturating coverage of interventions for reducing the burden of childhood illnesses in Low and Middle Income Countries (LMIC) is the lack of human resources. Community health workers (CHW) are potentially important actors in bridging this gap. Evidence exists on effectiveness of CHW in management of some childhood illnesses (IMCI). However, we need to know how and when this comes to be. We examine evidence from randomized control trials (RCT) on CHW interventions in IMCI in LMIC from a realist perspective with the aim to see if they can yield insight into the working of the interventions, when examined from a different perspective.</p> <p>Methods</p> <p>The realist approach involves educing the mechanisms through which an intervention produced an outcome in a particular context. 'Mechanisms' are reactions, triggered by the interaction of the intervention and a certain context, which lead to change. These are often only implicit and are actually hypothesized by the reviewer. This review is limited to unravelling these from the RCTs; it is thus a hypothesis generating exercise.</p> <p>Results</p> <p>Interventions to improve CHW performance included 'Skills based training of CHW', 'Supervision and referral support from public health services', 'Positioning of CHW in the community'. When interventions were applied in context of CHW programs embedded in local health services, with beneficiaries who valued services and had unmet needs, the interventions worked if following mechanisms were triggered: anticipation of being valued by the community; perception of improvement in social status; sense of relatedness with beneficiaries and public services; increase in self esteem; sense of self efficacy and enactive mastery of tasks; sense of credibility, legitimacy and assurance that there was a system for back-up support. Studies also showed that if context differed, even with similar interventions, negative mechanisms could be triggered, compromising CHW performance.</p> <p>Conclusion</p> <p>The aim of this review was to explore if RCTs could yield insight into the working of the interventions, when examined from a different, a realist perspective. We found that RCTs did yield some insight, but the hypotheses generated were very general and not well refined. These hypotheses need to be tested and refined in further studies.</p

Prevalence of 22q11.2 microdeletion in 146 patients with cardiac malformation in a referral hospital of North India

<p>Abstract</p> <p>Background</p> <p>The 22q11.2 microdeletion syndrome is a common condition that is associated with cardiac as well as extra-cardiac manifestations. Its prevalence and manifestations from north India has not been reported. This study was designed to determine the prevalence and ability of clinical criteria to predict 22q11.2 microdeletion.</p> <p>Methods</p> <p>A total of 146 cases of cardiac malformation requiring tertiary care at a teaching hospital were prospectively screened for 22q11.2 microdeletion using fluorescence in situ hybridization test. Detailed clinical information was obtained as per guidelines of Tobias, <it>et al </it>(1999).</p> <p>Results</p> <p>Nine out of 146 patients (6.16%) was found to have 22q11.2 microdeletion. All the positive patients showed the presence of extra-cardiac features of 22q11.2 microdeletion syndrome. None of the cases with isolated cardiac defect were positive for microdeletion.</p> <p>Conclusions</p> <p>It seems that 22q11.2 microdeletion syndrome is over-suspected in children with isolated congenital heart defects. Screening for 22q11.2 microdeletion should be considered in those cardiac malformation cases which have extra-cardiac manifestations in the form of facial dysmorphism and hypocalcaemia.</p