The educational value of ward rounds as a learning and teaching opportunity for house officers, medical officers, and registrars in Sudanese hospitals: a multi-center cross-sectional study.

BACKGROUND: Ward rounds are a cornerstone in the educational experience of junior doctors and an essential part of teaching patient care. Here, we aimed to assess the doctors' perception of ward rounds as an educational opportunity and to identify the obstacles faced in conducting a proper ward round in Sudanese hospitals. METHOD: A cross-sectional study was conducted from the 15th to the 30th of January 2022 among house officers, medical officers, and registrars in about 50 teaching and referral hospitals in Sudan. House officers and medical officers were considered the learners, while specialist registrars were considered the teachers. Doctors' perceptions were assessed using an online questionnaire, with a 5-level Likert scale to answer questions. RESULTS: A total of 2,011 doctors participated in this study (882 house officers, 697 medical officers, and 432 registrars). The participants were aged 26.9 ± 3.2 years, and females constituted about 60% of the sample. An average of 3.1 ± 6.8 ward rounds were conducted per week in our hospitals, with 11.1 ± 20.3 h spent on ward rounds per week. Most doctors agreed that ward rounds are suitable for teaching patient management (91.3%) and diagnostic investigations (89.1%). Almost all the doctors agreed that being interested in teaching (95.1%) and communicating appropriately with the patients (94.7%) make a good teacher in ward rounds. Furthermore, nearly all the doctors agreed that being interested in learning (94.3%) and communicating appropriately with the teacher (94.5%) make a good student on ward rounds. About 92.8% of the doctors stated that the quality of ward rounds could be improved. The most frequently reported obstacles faced during ward rounds were the noise (70%) and lack of privacy (77%) in the ward environment. CONCLUSION: Ward rounds have a special value in teaching patient diagnosis and management. Being interested in teaching/learning and having good communication skills were the two major criteria that make a good teacher/learner. Unfortunately, ward rounds are faced with obstacles related to the ward environment. It is mandatory to ensure the quality of both ward rounds' teaching and environment to optimize the educational value and subsequently improve patient care practice.

Flexible Antenna with Circular/Linear Polarization for Wideband Biomedical Wireless Communication.

A wideband low-profile radiating G-shaped strip on a flexible substrate is proposed to operate as biomedical antenna for off-body communication. The antenna is designed to produce circular polarization over the frequency range 5-6 GHz to communicate with WiMAX/WLAN antennas. Furthermore, it is designed to produce linear polarization over the frequency range 6-19 GHz for communication with the on-body biosensor antennas. It is shown that an inverted G-shaped strip produces circular polarization (CP) of the opposite sense to that produced by G-shaped strip over the frequency range 5-6 GHz. The antenna design is explained and its performance is investigated through simulation, as well as experimental measurements. This antenna can be viewed as composed of a semicircular strip terminated with a horizontal extension at its lower end and terminated with a small circular patch through a corner-shaped strip extension at its upper end to form the shape of "G" or inverted "G". The purpose of the corner-shaped extension and the circular patch termination is to match the antenna impedance to 50 Ω over the entire frequency band (5-19 GHz) and to improve the circular polarization over the frequency band (5-6 GHz). To be fabricated on only one face of the flexible dielectric substrate, the antenna is fed through a co-planar waveguide (CPW). The antenna and the CPW dimensions are optimized to obtain the most optimal performance regarding the impedance matching bandwidth, 3dB Axial Ratio (AR) bandwidth, radiation efficiency, and maximum gain. The results show that the achieved 3dB-AR bandwidth is 18% (5-6 GHz). Thus, the proposed antenna covers the 5 GHz frequency band of the WiMAX/WLAN applications within its 3dB-AR frequency band. Furthermore, the impedance matching bandwidth is 117% (5-19 GHz) which enables low-power communication with the on-body sensors over this wide range of the frequency. The maximum gain and radiation efficiency are 5.37 dBi and 98%, respectively. The overall antenna dimensions are 25 × 27 × 0.13 mm3 and the bandwidth-dimension ratio (BDR) is 1733.

Serum interleukin 1ß and sP-selectin as biomarkers of inflammation and thrombosis, could they be predictors of disease severity in COVID 19 Egyptian patients? (a cross-sectional study).

BACKGROUND: Thromboembolism was a chief cause of mortality in 70% of patients with COVID-19. Our objective was to see if serum interleukins 1 beta (IL-1ß) and soluble platelets selectin (sP-selectin) could serve as novel markers of thromboembolism in COVID-19 patients. METHODS: This cross sectional study involved 89 COVID-19 patients who were recruited from 1st of February to 1st of May 2021. Clinical and laboratory data were collected, and chest imaging was performed. The levels of IL-1ß and sP-selectin were assessed in all cases through ELISA kits. Comparisons between groups were done using an unpaired t-test in normally distributed quantitative variables. In contrast, a non-parametric Mann-Whitney test was used for non-normally distributed quantitative variables. RESULTS: Severe COVID-19 infection was associated with higher serum levels of CRP, Ferritin, LDH, D dimer, IL-1ß and sP-selectin (P <  0.001) with significant correlation between levels of IL-1ß and sP-selectin (r 0.37, P <  0.001), D-dimer (r 0.29, P 0.006) and Ferritin (r 0.5, p <  0.001). Likewise, a positive correlation was also found between levels of sP-selectin, D-dimer and Ferritin (r 0.52, P <  0.001) (r 0.59, P <  0.001). Imaging studies revealed that 9 (10.1%) patients developed venous and 14 (15.7%) developed arterial thrombosis despite receiving anticoagulant therapy. Patients with thrombotic events had significantly higher levels of IL-1ß, sP-selectin and LDH serum levels. Meanwhile, there was no statistical significance between CRP, D-dimer or Ferritin levels and the development of thrombotic events. CONCLUSION: IL-1ß and sP-selectin levels can be promising predictors for severe COVID-19 infection and predictable thrombosis.

Comparison of bone regenerative capacity of donor-matched human adipose-derived and bone marrow mesenchymal stem cells.

Adipose-derived stem cells (ASC) have been used as an alternative to bone marrow mesenchymal stem cells (BMSC) for bone tissue engineering. However, the efficacy of ASC in bone regeneration in comparison with BMSC remains debatable, since inconsistent results have been reported. Comparing ASC with BMSC obtained from different individuals might contribute to this inconsistency in results. Therefore, this study aimed to compare the bone regenerative capacity of donor-matched human ASC and BMSC seeded onto poly(L-lactide-co-ε-caprolactone) scaffolds using calvarial bone defects in nude rats. First, donor-matched ASC and BMSC were seeded onto the co-polymer scaffolds to evaluate their in vitro osteogenic differentiation. Seeded scaffolds and scaffolds without cells (control) were then implanted in calvarial defects in nude rats. The expression of osteogenesis-related genes was examined after 4 weeks. Cellular activity was investigated after 4 and 12 weeks. Bone formation was evaluated radiographically and histologically after 4, 12, and 24 weeks. In vitro, ASC and BMSC demonstrated mineralization. However, BMSC showed higher alkaline phosphatase activity than ASC. In vivo, human osteogenesis-related genes Runx2 and collagen type I were expressed in defects with scaffold/cells. Defects with scaffold/BMSC had higher cellular activity than defects with scaffold/ASC. Moreover, bone formation in defects with scaffold/BMSC was greater than in defects with scaffold/ASC, especially at the early time-point. These results suggest that although ASC have the potential to regenerate bone, the rate of bone regeneration with ASC may be slower than with BMSC. Accordingly, BMSC are more suitable for bone regenerative applications.

Printability and Critical Insight into Polymer Properties during Direct-Extrusion Based 3D Printing of Medical Grade Polylactide and Copolyesters.

Various 3D printing techniques currently use degradable polymers such as aliphatic polyesters to create well-defined scaffolds. Even though degradable polymers are influenced by the printing process, and this subsequently affects the mechanical properties and degradation profile, degradation of the polymer during the process is not often considered. Degradable scaffolds are today printed and cell-material interactions evaluated without considering the fact that the polymer change while printing the scaffold. Our methodology herein was to vary the printing parameters such as temperature, pressure, and speed to define the relationship between printability, polymer microstructure, composition, degradation profile during the process, and rheological behavior. We used high molecular weight medical-grade (co)polymers, poly(l-lactide-co-ε-caprolactone) (PCLA), poly(l-lactide-co-glycolide) (PLGA), and poly(d,l-lactide-co-glycolide) (PDLGA), with l-lactide content ranging from 25 to 100 mol %, for printing in an extrusion-based printer (3D Bioplotter). Optical microscopy confirmed that the polymers were printable at high resolution and good speed, until a certain degree of degradation. The results show also that printability can not be claimed just by optimizing printing parameters and highlight the importance of a careful analysis of how the polymer's structure and properties vary during printing. The polymers thermally decomposed from the first processing minute and caused a decrease in the average block length of the lactide blocks in the copolymers and generated lower crystallinity. Poly(l-lactide) (PLLA) and PCLA are printable at a higher molecular weight, less degradation before printing was possible, compared to PLGA and PDLGA, a result explained by the higher complex viscosity and more elastic polymeric melt of the copolymer containing glycolide (GA) and lactide (LA). In more detail, copolymers comprised of LA and ε-caprolactone (CL) formed lower molecular weight compounds over the course of printing, while the PLGA copolymer was more susceptible to intermolecular transesterification reactions, which do not affect the overall molecular weight, but cause changes in the copolymer microstructure. This results in a longer printing time for PLGA than PLLA and PCLA.

Maps of variability in cell lineage trees.

New approaches to lineage tracking have allowed the study of differentiation in multicellular organisms over many generations of cells. Understanding the phenotypic variability observed in these lineage trees requires new statistical methods. Whereas an invariant cell lineage, such as that for the nematode Caenorhabditis elegans, can be described by a lineage map, defined as the pattern of phenotypes overlaid onto the binary tree, a traditional lineage map is static and does not describe the variability inherent in the cell lineages of higher organisms. Here, we introduce lineage variability maps which describe the pattern of second-order variation in lineage trees. These maps can be undirected graphs of the partial correlations between every lineal position, or directed graphs showing the dynamics of bifurcated patterns in each subtree. We show how to infer these graphical models for lineages of any depth from sample sizes of only a few pedigrees. This required developing the generalized spectral analysis for a binary tree, the natural framework for describing tree-structured variation. When tested on pedigrees from C. elegans expressing a marker for pharyngeal differentiation potential, the variability maps recover essential features of the known lineage map. When applied to highly-variable pedigrees monitoring cell size in T lymphocytes, the maps show that most of the phenotype is set by the founder naive T cell. Lineage variability maps thus elevate the concept of the lineage map to the population level, addressing questions about the potency and dynamics of cell lineages and providing a way to quantify the progressive restriction of cell fate with increasing depth in the tree.

Yield of household contact investigation of patients with pulmonary tuberculosis in southern Ethiopia.

BACKGROUND: Household Contacts (HHCs) of patients with pulmonary tuberculosis (PTB) have a higher risk of developing TB. Contact investigation is recommended to reach this group and identify undiagnosed cases. In this study, we have determined the yield of contact investigation among HHCs of patients with smear-positive PTB, and estimated TB burden. METHODS: We conducted retrospective record review for the occurrence of TB among HHCs of Index PTB+ cases treated between November 2010 and April 2013 in 12 public health facilities in Boricha district. HHCs were followed up monthly and revisited between March and June 2015. Information on additional TB cases diagnosed and treated among HHCs were documented. HHCs who were diagnosed as having TB after the index cases were diagnosed and treated were considered as 'incident cases'. Presumptive TB case was defined as those having cough for ≥2 weeks or enlarged lymph node. Diagnosis of TB among HHCs were made using smear-microscopy and/or X-rays, and clinically for Extra-pulmonary TB (EPTB). RESULTS: One thousand five hundred and seventeenth HHCs of 344 index cases were visited and screened for TB and followed up for a median of 37 months. 77 (5.1% - 72 with PTB and 5 with EPTB) HHCs developed TB during 4713 person-years of follow-up with an estimated incidence of 1634 (95% CI: 1370-2043) per 100,000 person-years follow-up which is much higher than the estimated TB incidence for the general population in Ethiopia of 210/100,000. Half (41/77) of incident TB cases were diagnosed within the first year of diagnosis of the index cases and 88% (68/77) were adults (Hazard Ratio: 4.03; 95% CI: 2.00-8.12). CONCLUSION: HHCs of index PTB+ cases have high risk of developing active TB. Long term follow-up of HHCs could help improve TB case finding depending on country contexts. Further studies on effectiveness and feasibility of the approach and integration in routine settings are needed.

Synthesis of Hydroxybenzofuranyl-pyrazolyl and Hydroxyphenyl-pyrazolyl Chalcones and Their Corresponding Pyrazoline Derivatives as COX Inhibitors, Anti-inflammatory and Gastroprotective Agents.

Five new series of hydroxybenzofuranyl-pyrazolyl chalcones 3a,b, hydroxyphenyl-pyrazolyl chalcones 6a-c and their corresponding pyrazolylpyrazolines 4a, d, 7a-c and 8a-f have been synthesized and evaluated for their in vitro cyclooxygenase (COX)-1 and COX-2 inhibitory activity. All the synthesized compounds exhibited dual COX-1 and COX-2 inhibitory activity with obvious selectivity against COX-2. The pyrazolylpyrazolines 4a-d and 8a-f bearing two vicinal aryl moieties in the pyrazoline nucleus showed more selectivity towards COX-2. Within these two series, derivatives 4c, d and 8d-f bearing the benzenesulfonamide group were the most selective. Compounds 4a-d and 8a-f were further subjected to in vivo anti-inflammatory screening, ulcerogenic liability and showed good anti-inflammatory activity with no ulcerogenic effect. In addition compounds 4c and 8d as examples showed prostaglandin (PG)E2 inhibition % 44.23 and 51.4 respectively, tumor necrosis factor α (TNFα) inhibition % 33.48 and 41.41 respectively and gastroprotective effect in ethanol induced rodent gastric ulcer model. In addition, to explore the binding mode and selectivity of our compounds, 8d and celecoxib were docked into the active site of COX-1 and COX-2. It was found that compound 8d exhibited a binding pattern and interactions similar to that of celecoxib with COX-2 active site, while bitter manner of interaction than celecoxib to COX-1 active site.

Factors contributing to drug-resistant tuberculosis treatment outcome in five countries in the Eastern Europe and Central Asia region.

Drug-resistant tuberculosis (DR-TB) is a global challenge and a major contributor of death from anti-microbial resistance. With the main aim to determine factors contributing to treatment outcomes observed among DR-TB patients in the countries in Eastern Europe and Central Asia (EECA), a multi-method study was conducted in: Azerbaijan, Belarus, Romania, Tajikistan and Ukraine. Both quantitative and qualitative methodologies were used for data collection and analysis. The quantitative approaches included a desk review of documents related to the DR-TB responses and an analysis of clinical records of DR-TB patients in selected health facilities of the five countries. Qualitative methods included in-depth interviews with national TB programme (NTP) managers, other healthcare providers and non-governmental organizations (NGOs) workers, as well as interviews and Focus Group Discussions (FGDs) with DR-TB patients. The desk review of 38 reports identified as the main challenges to address DR-TB financial and/or management issues and adverse events of the medicines. The most common recommendations related to treatment outcome focussed on general programme management, treatment regimen composition, clinical management and social support for the patients. In all the five countries the NTPs still have a vertical structure. Some integration into the primary health care system (PHC) already exists but further involvement of PHC facilities is feasible and recommended. Interviews with stakeholders indicated that alcoholism and homelessness and a lack of appropriate response to these issues remain as major challenges for a sub-set of patients. Civil society groups, NGOs and communities are substantially engaged in providing different services to DR-TB patients, especially in Ukraine, Romania and Tajikistan. Data from clinical records of 212 patients revealed that independent risk factors for unfavourable treatment outcome (death, loss to follow-up, failure) were culture-positivity at two months of treatment, history of treatment with second-line drugs and homelessness. More powerful, less toxic and shorter oral treatment regimens as well as comprehensive patient support are needed to improve treatment outcome of patients with DR-TB.

Sub-national prevalence survey of tuberculosis in rural communities of Ethiopia.

BACKGROUND: Tuberculosis is a major public health problem with varying prevalence in different settings. National prevalence surveys provide evidence for planning and decision making. However, they lack the capacity to estimate subnational magnitude that affected the capacity to make selected intervention based on the prevalence. Ethiopia is among high TB burden countries with estimated prevalence of 108 per 100,000 population varying by regions. We aimed to study sub national prevalence of smear-positive TB in rural communities of southern Ethiopia. METHODS: This cross-sectional study, enrolled community members aged over 14 years who had cough of at least two weeks duration. Two sputum samples were collected and examined by using smear microscopy. RESULTS: 38,304 eligible people were enumerated (10,779 from Hadiya, 10,059 from Gurage and 17,466 from Sidama) and indentified 960 presumptive cases. 16, 14 and 14 smear-positive pulmonary TB cases were identified respectively. The point prevalence of smear-positive TB were 148 per 100,000 population (95% CI: 91-241) in Hadiya, 139 per 100,000 population (95% CI: 83-234) in Gurage and 80/100,000 population (95%CI: 48-135) in Sidama zone. Gurage zone had the highest prevalent to notified cases of seven to one. CONCLUSIONS: The prevalence of smear positive TB varies by districts and is high in rural southern Ethiopia compared to the estimated national prevalence. More TB patients remain missed and unreached, impacting negatively on health outcomes. TB case finding approaches should be revisited and innovative approaches and tools to identify missing people with TB should be scaled up.

Evaluation of Apical Dimension, Canal Taper and Maintenance of Root Canal Morphology Using XP-endo Shaper.

AIM: To evaluate the shaping ability of the XP-endo shaper file system in maxillary molars, representing root canals with variation in morphology. MATERIALS AND METHODS: Twenty maxillary molars were instrumented according to recommended protocols. Pre- and postoperative microcomputed tomography (CT) scans were performed and the root canals classified according to canal type and curvature. The volume change, number of strokes needed to prepare the canals and the size of the 0.04-tapered gutta-percha cone that was adapted in the canal were recorded. RESULTS: XP-endo shaper created a significant change in volume after instrumentation in all the canals, with the biggest change found in the DB canals, followed by the MB1 and the P canals, both at full length and in the apical 4 mm. The number of strokes needed to achieve working length and final shape did not differ between the various root canals. Although not significant, the number of strokes needed to prepare the root canal increased with severity of the curvature, but the severity of the curvature did not result in increased removal of dentin in the apical 4 mm. It was possible to achieve a final root canal size where a 0.04-tapered gutta-percha cone could be adapted. CONCLUSION: The XP-endo shaper was a safe and effective instrument to achieve a root canal preparation of at least size 30 and a 0.04 taper. CLINICAL SIGNIFICANCE: The clinical performance of XP-endo shaper was to some extent dependent on preoperative volume and curvature of the root canal.

Coating 3D Printed Polycaprolactone Scaffolds with Nanocellulose Promotes Growth and Differentiation of Mesenchymal Stem Cells.

3D printed polycaprolactone (PCL) has potential as a scaffold for bone tissue engineering, but the hydrophobic surface may hinder optimal cell responses. The surface properties can be improved by coating the scaffold with cellulose nanofibrils material (CNF), a multiscale hydrophilic biocompatible biomaterial derived from wood. In this study, human bone marrow-derived mesenchymal stem cells were cultured on tissue culture plates (TCP) and 3D printed PCL scaffolds coated with CNF. Cellular responses to the surfaces (viability, attachment, proliferation, and osteogenic differentiation) were documented. CNF significantly enhanced the hydrophilic properties of PCL scaffolds and promoted protein adsorption. Live/dead staining and lactate dehydrogenase release assays confirmed that CNF did not inhibit cellular viability. The CNF between the 3D printed PCL strands and pores acted as a hydrophilic barrier, enhancing cell seeding efficiency, and proliferation. CNF supported the formation of a well-organized actin cytoskeleton and cellular production of vinculin protein on the surfaces of TCP and PCL scaffolds. Moreover, CNF-coated surfaces enhanced not only alkaline phosphatase activity, but also collagen Type-I and mineral formation. It is concluded that CNF coating enhances cell attachment, proliferation, and osteogenic differentiation and has the potential to improve the performance of 3D printed PCL scaffolds for bone tissue engineering.

Clinical and molecular response to interferon-α therapy in essential thrombocythemia patients with CALR mutations.

Myeloproliferative neoplasms are clonal disorders characterized by the presence of several gene mutations associated with particular hematologic parameters, clinical evolution, and prognosis. Few therapeutic options are available, among which interferon α (IFNα) presents interesting properties like the ability to induce hematologic responses (HRs) and molecular responses (MRs) in patients with JAK2 mutation. We report on the response to IFNα therapy in a cohort of 31 essential thrombocythemia (ET) patients with CALR mutations (mean follow-up of 11.8 years). HR was achieved in all patients. Median CALR mutant allelic burden (%CALR) significantly decreased from 41% at baseline to 26% after treatment, and 2 patients even achieved complete MR. In contrast, %CALR was not significantly modified in ET patients treated with hydroxyurea or aspirin only. Next-generation sequencing identified additional mutations in 6 patients (affecting TET2, ASXL1, IDH2, and TP53 genes). The presence of additional mutations was associated with poorer MR on CALR mutant clones, with only minor or no MRs in this subset of patients. Analysis of the evolution of the different variant allele frequencies showed that the mutated clones had a differential sensitivity to IFNα in a given patient, but no new mutation emerged during treatment. In all, this study shows that IFNα induces high rates of HRs and MRs in CALR-mutated ET, and that the presence of additional nondriver mutations may influence the MR to therapy.

Digital health for the End TB Strategy: developing priority products and making them work.

In 2014, the World Health Organization (WHO) developed the End TB Strategy in response to a World Health Assembly Resolution requesting Member States to end the worldwide epidemic of tuberculosis (TB) by 2035. For the strategy's objectives to be realised, the next 20 years will need novel solutions to address the challenges posed by TB to health professionals, and to affected people and communities. Information and communication technology presents opportunities for innovative approaches to support TB efforts in patient care, surveillance, programme management and electronic learning. The effective application of digital health products at a large scale and their continued development need the engagement of TB patients and their caregivers, innovators, funders, policy-makers, advocacy groups, and affected communities.In April 2015, WHO established its Global Task Force on Digital Health for TB to advocate and support the development of digital health innovations in global efforts to improve TB care and prevention. We outline the group's approach to stewarding this process in alignment with the three pillars of the End TB Strategy. The supplementary material of this article includes target product profiles, as developed by early 2016, defining nine priority digital health concepts and products that are strategically positioned to enhance TB action at the country level.

Countdown to 2015 country case studies: what can analysis of national health financing contribute to understanding MDG 4 and 5 progress?

BACKGROUND: Countdown to 2015 (Countdown) supported countries to produce case studies that examine how and why progress was made toward the Millennium Development Goals (MDGs) 4 and 5. Analysing how health-financing data explains improvements in RMNCH outcomes was one of the components to the case studies. METHODS: This paper presents a descriptive analysis on health financing from six Countdown case studies (Afghanistan, Ethiopia, Malawi, Pakistan, Peru, and Tanzania), supplemented by additional data from global databases and country reports on macroeconomic, health financing, demographic, and RMNCH outcome data as needed. It also examines the effect of other contextual factors presented in the case studies to help interpret health-financing data. RESULTS: Dramatic increases in health funding occurred since 2000, where the MDG agenda encouraged countries and donors to invest more resources on health. Most low-income countries relied on external support to increase health spending, with an average 20-64 % of total health spending from 2000 onwards. Middle-income countries relied more on government and household spending. RMNCH funding also increased since 2000, with an average increase of 119 % (2005-2010) for RMNH expenditures (2005-2010) and 165 % for CH expenditures (2005-2011). Progress was made, especially achieving MDG 4, even with low per capita spending; ranging from US$16 to US$44 per child under 5 years among low-income countries. Improvements in distal factors were noted during the time frame of the analysis, including rapid economic growth in Ethiopia, Peru, and Tanzania and improvements in female literacy as documented in Malawi, which are also likely to have contributed to MDG progress and achievements. CONCLUSIONS: Increases in health and RMNCH funding accompanied improvements in outcomes, though low-income countries are still very reliant on external financing, and out-of-pocket comprising a growing share of funds in middle-income settings. Enhancements in tracking RMNCH expenditures across countries are still needed to better understand whether domestic and global health financing initiatives lead to improved outcomes as RMNCH continues to be a priority under the Sustainable Development Goals.

Novel Sulfonamide Derivatives Carrying a Biologically Active 3,4-Dimethoxyphenyl Moiety as VEGFR-2 Inhibitors.

Novel sulfonamides 3-19 with a biologically active 3,4-dimethoxyphenyl moiety were designed and synthesized. The structures of the synthesized compounds were established using elemental analyses, IR, 1H-NMR, 13C-NMR spectral data and mass spectroscopy. All the synthesized compounds were evaluated for their in vitro anticancer activity against four cancer cell lines, namely human hepatocellular carcinoma (HepG2), human medulloblastoma (Daoy), human cervical cancer (HeLa), and human colon cancer (HT-29), by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and dasatinib as the reference drug. Among the tested derivatives, compounds 4, 10, 16, and 19 showed good activity as cytotoxic agents. The most active derivatives were evaluated for their ability to inhibit vascular endothelial growth factor receptor (VEGFR)-2. Compounds Z-4-(3-(3,4-dimethoxyphenyl)-3-oxoprop-1-enylamino)-N-(5-methyl-1,3,4-thiadiazol-2-yl)-benzenesulfonamide 10 and Z-4-(3-(3,4-dimethoxyphenyl)-3-oxoprop-1-enylamino)-N-(1H-indazol-6-yl)-benzenesulfonamide 19 were more active as VEGFR-2 inhibitors than dasatinib. Molecular docking of the most active derivatives on the active site of VEGFR-2 revealed that compound 19 exhibited favorable and promising results.

Patient and community experiences of tuberculosis diagnosis and care within a community-based intervention in Ethiopia: a qualitative study.

BACKGROUND: The Ethiopian TB control programme relies on passive case finding of TB cases. The predominantly rural-based population in Ethiopia has limited access to health facilities creating barriers to TB services. An intervention package aimed to bring TB diagnosis and treatment services closer to communities has been implemented through partnership with health extension workers (HEWs). They undertook advocacy, communication and social mobilization (ACSM) activities, identified symptomatic individuals, collected sputum, prepared smears and fixed slides at community level. Field supervisors supported HEWs by delivering smeared slides to the laboratory, feeding back results to the HEWs and following up smear-negative cases. Patients diagnosed with TB initiated treatment in the community, they were supported by supervisors and HEWs through the local health post. Case notification increased from 64 to 127/100,000 population/year. METHODS: This qualitative study assessed community members' treatment seeking behaviour and their perceptions of the intervention. In-depth interviews (n=36) were undertaken with participants in six districts. Participants were clients of the community-based intervention, currently on TB treatment or those screened negative for TB. Transcripts were translated to English and a thematic analytical framework was developed guided by the different steps symptomatic individuals take within the intervention package. Coding was done and queries run using NVivo software. RESULTS: Prior to the intervention many patients with chronic cough did not access TB services. Participants described difficulties they faced in accessing district level health facilities that required travel outside their communities. Giving sputum samples and receiving results from within their home communities was appreciated by all participants. The intervention had a high level of acceptability; particularly clear benefits emerged for poor women and men and those too weak to travel. Some participants appeared to prefer a diagnosis of TB, this is likely because receiving a negative smear microscopy result brought further uncertainty and necessitated seeking further investigation. CONCLUSIONS: There is evidence rural populations with high levels of poverty, and in particular women, are at high risk of unmet health needs and undiagnosed TB. Embedding TB services within communities was an acceptable approach for vulnerable groups experiencing poor access to health facilities. In the Ethiopian context this approach can facilitate early diagnosis and improve treatment outcomes.

Exploring providers' perspectives of a community based TB approach in Southern Ethiopia: implication for community based approaches.

BACKGROUND: There is increasing interest in the role of close-to-community providers in supporting universal health coverage, but questions remain about the best approaches to supporting and motivating these providers, and the optimal package they can deliver indifferent contexts and support required. We report on the experiences of different health providers involved in a community based intervention to support access to tuberculosis diagnosis and treatment in Southern Ethiopia. METHODS: The aim of the study is to explore the experiences of health providers in delivering a community-based tuberculosis package in southern Ethiopia and to draw lessons for community-based programmes. A qualitative methodology was used. Methods included in-depth interviews (IDIs, n= 37) with all health provider groups: Community health promoters (CHPs), health extension workers (HEWs), district supervisors and laboratory technicians were undertaken to obtain a detailed understanding of the experiences of providers in the community based tuberculosis package. These were complemented with cadre specific focus group discussions (n= 3). We used the framework approach for qualitative analysis. RESULTS: The key theme that emerged was the positive impact the community-based intervention had on vulnerable groups' access to diagnosis, care and treatment for tuberculosis. Providers found the positive feedback from, and visible impact on, communities very motivating. Other themes related to motivation and performance included supervision and support; learning new skills; team problem solving/ addressing challenges and incentives. Against the backdrop of the Ethiopian Health Extension Programme (HEP), HEWs were successfully able to take on new tasks (collecting sputum and preparing smears) with additional training and appropriate support from supervisors, laboratory technicians and CHPs. CONCLUSION: All categories of providers were motivated by the high visible impact of the community-based intervention on poor and vulnerable communities and households. HEWs role in the community-based intervention was supported and facilitated through the structures and processes established within the community-based intervention and the broader nation-wide Health Extension Programme. Within community based approaches there is need to develop context embedded strategies to support, sustain and motivate this critical cadre who play a pivotal role in linking health systems and rural communities.

TACTICS, an interactive platform for customized high-content bioimaging analysis.

We describe a modular MATLAB® Toolbox named TACTICS for time-lapse image analysis that meets several requirements not generally offered by currently available software packages: (i) the ability to assess quality of extracted imaging information by directly linking data end points to the original position, (ii) massively parallel analysis of each parameter, for flow cytometry-like assessment of possible relationships between parameters within sub-populations of the images, (iii) options for user control of the tracking such as an interface to restrict the analysis region, (iv) manual correction of automated processes and (v) user interfaces for post-tracking analysis that is linked to the original images, including options to view cell pedigrees and normalized polarization ratios based on fluorescence ratiometric measurements.

Synthesis and biological evaluation of new pyrazolone-pyridazine conjugates as anti-inflammatory and analgesic agents.

A new series of pyrazolone-pyridazine conjugates 3 and 4a-l were synthesized and characterized by spectroscopic means and elemental analyses. All compounds were tested in vivo for their anti-inflammatory and analgesic properties against diclofenac, as reference compound. The synthesized compounds were also evaluated for their ability to inhibit the production of certain inflammatory cytokines such as TNF-α and IL-6 in serum samples. The ulcerogenic potential of the synthesized compounds was also determined. IC50 values for inhibition of COX-1 and COX-2 enzymes were investigated in vitro for the most active candidates. Molecular docking was performed on the active site of COX-2 to predict their mode of binding to the amino acids. Among the synthesized derivatives, compounds 4c and 4e showed good analgesic and anti-inflammatory activities with lower ulcer index than the reference drug.