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Abstract Background Even though the urban health extension program (HEP) has been implemented since 2009, little was known about its implementation, experience and challenges. Therefore, this study was aimed at exploring the implementation, experience, and challenges of the urban HEP. Methods A qualitative case study was conducted in Addis Ababa from November 15 to December 29, 2017. The study participants were recruited purposefully. The parent populations were health extension professionals (HEPs). However, health post supervisors, health development army leaders (HDAs), Addis Ababa city HEP administrators, and other community members were also involved in the study. Four focus group discussions and 31 in-depth and key informant interviews were conducted. Data were transcribed verbatim, translated into the English, and analyzed by an inductive thematic analysis approach using Atlas ti7.1 software. Result The study found that there were 15 health service packages of the urban HEP delivered to the community based on the need of the households. The strategies for the program implementation were provision of trainings, home visitation, creation of model households, strengthening of HDAs, supervision and reporting, referral and feedback, and social and community mobilization. However, program implementation was challenged by the health system related challenges (health service package and delivery, workload of HEPs, shortage of trained HEPs, lack of regular supervision or monitoring, lack of logistical or motivational support, poor supply chain management, dissatisfaction of HEPs, assigning of more than expected households for HEPs, etc.), multisectoral related and community related challenges (HDAs need of incentives, and lack of graduating model households as per the plan, etc.). Conclusions Although the program had a significant contribution to the health of community, it was affected by different challenges that underscore the need to develop different strategies and taking of actions. Therefore, the district health office, health centers and stakeholders from different sectors should have to support and motivate the HEPs and HDAs, and work together with them for successful implementation of the program.

Key Clinical Message: Concomitant native and prosthetic valve infective endocarditis (IE) is very rare, and both can rarely be complicated by rapidly progressive glomerulonephritis (RPGN). This diagnosis has therapeutic implications, as not all RPGN need immunosuppression therapy., Abstract: Native and prosthetic valve infective endocarditis (IE) may be rarely complicated by rapidly progressive glomerulonephritis (RPGN). The diagnosis of IE as a cause of RPGN may be missed, and patients may be subjected to inappropriate immune suppressive therapy. Moreover, IE involving multi-valves has rarely been described, and there are only few case reports of simultaneous native and prosthetic valve endocarditis. Here, we present a case of 34-year-old female patient who has RPGN and whose initial workup missed IE. However, further workup revealed a diagnosis of native and prosthetic valve IE and our patient, who would have been subjected to inappropriate immune suppressive therapy, was treated with intravenous antibiotics alone and discharged with improvement., Competing Interests: The authors authors have no conflict of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

In this research, a brick kiln integrated with pollutant emission control technology was designed and applied in order to produce charcoal from Eucalyptus Globules wood. The batch operation carbonization of wood biomass was undertaken in a 1.25 m 3 volume brick kiln. A wet-packed scrubber was designed and constructed by filling gravels in a depth of 40 cm with aggregate sizes of 48-60 mm, 27-33 mm and 16-20 mm from the bottom to the top respectively aiming to treat emission from the charcoal-producing unit. The characteristics of the charcoal produced were determined to be composed of 9% moisture content, 1.5% ash content, 38% charcoal yield and a heating value of 27.53 MJ/kg. On the other hand, the wet scrubber integrated into a brick kiln was found to remove Hydrocarbons, C O 2 and CO by 97.8%, 98.5% and 99% respectively, which makes it efficient and practical way of controlling the gasses released during producing of charcoal., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Key Clinical Message: Low threshold is required to suspect complications of Plasmodium vivax malaria. Pulmonary thromboembolism, though rare, should be considered as its complication in the presence of unexplained and sudden onset shortness of breath., Abstract: The hypercoagulable complications of malaria typically manifest in the microvasculature. However, there are several cases of intracranial venous thrombosis caused by Plasmodium falciparum and Plasmodium vivax malaria, and there was one case report of pulmonary thromboembolism (PTE) due to P. falciparum . A 30-year-old Ethiopian male patient presented with sudden onset of shortness of breath for 3 days. He had also high-grade fever, chills, and rigors associated with loss of appetite and fatigue of similar duration. He was from malaria endemic area. He had a pulse rate of 108 beats per minutes, respiratory rate of 32 breaths per minute, oxygen saturation of 82% with atmospheric air and temperature of 38.9°C. Further examination revealed accentuation of pulmonary component of second heart sound. Complete blood count revealed mild anemia and peripheral blood film showed trophozoites of P. vivax . Pulmonary CT angiography showed filling defects in the right and left pulmonary arteries. The patient was diagnosed to have P. vivax malaria complicated by PTE. He was managed with intranasal oxygen, antimalarial agent, and anticoagulation. Upon serial evaluations on the third week and second month of follow up, he did not have complaints and physical examination was non-remarkable. Malaria is a protozoan disease with high mortality and morbidity. For a long time, severe cases of malaria were thought to be mostly caused by P. falciparum . However, recent evidences have shown a paradigm shift and we should remember that P. vivax can also cause severe malaria and this can be complicated by hypercoagulable conditions including PTE., Competing Interests: The authors declared no potential conflicts of interest., (© 2023 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Background: People living with human immunodeficiency virus (HIV) are facing an increased burden of noncommunicable diseases (NCDs) comorbidity. There is, however, paucity of information on the magnitude of HIV-NCDs comorbidity, its associated factors, and how the health system is responding to the double burden in Ethiopia., Objective: To determine the magnitude of comorbidity between HIV and hypertension or diabetes and associated factors among HIV-positive adults receiving antiretroviral therapy (ART) in Bahir Dar city, Ethiopia., Methods: A facility-based cross-sectional study was conducted among 560 randomly selected HIV-positive adults taking ART. Data were collected using a structured questionnaire and analyzed using SPSS version 23. Descriptive statistics were used to describe the data. A logistic regression model was fit to identify associated factors with comorbidity of HIV and NCDs., Results: The magnitude of comorbidity was 19.6% (95% confidence interval (CI): 16.0-23.0). Being older (55 and above years) adjusted odds ratio (AOR: 8.5; 95% CI: 3.2-15.1), taking second-line ART regimen containing tenofovir (AOR: 2.7; 95% CI: 1.3-5.6), and increased body mass index (BMI) ≥25 (AOR: 2.7; 95% CI: 1.2-6.5) were the factors associated with comorbidity. Participants reported that they were not managed in an integrated and coordinated manner., Conclusions: The magnitude of comorbidity among adults was high in the study area. Being older, second-line ART regimen and high BMI ≥25 increased the odds of having NCDs among HIV-positive adults. Targeted screening for the incidences of NCDs, addressing modifiable risk factors, and providing integrated care would help to improve the quality of life comorbid patients., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Despite poverty reduction and increased promotion of improved nutrition practices in the community, undernutrition in Ethiopia remains a concern. The present study aimed to explore the demand and supply side barriers that limit the uptake of nutrition services among pregnant women from the rural communities of the Tigray Region, Northern Ethiopia. A community-based qualitative study was conducted in December through January 2017. A total of 90 key informant in-depth interviews and 14 focus group discussions were undertaken. Study participants were purposively selected for specific characteristics, along with health professionals deployed at various levels of the health system, including health posts, health centers, woreda health offices, and the regional health bureau. Study participants were asked to identify the barriers and implementation challenges that limit access to nutrition services for pregnant women. Participants' responses were transcribed verbatim, without editing the grammar, to avoid losing meaning. The data were imported to ATLAS.ti 7 (qualitative data analysis software) for coding and analyzed using a thematic content analysis approach. The study findings indicated that the dietary quality of pregnant women in the study area remains poor and in some cases, poorer quality than pre-pregnancy. Across study sites, heavy workloads, food taboos and avoidances, low husband support, lack of economic resources, lack of awareness, low educational level of women, poor dietary habits, increased expenditure for cultural and religious festivities, "dependency syndrome", low physical access to health facilities, poorly equipped health facilities, focus on child health and nutrition, poor coordination among nutrition specific and sensitive sectors, and limited sources of nutrition information were identified as the demand and supply side barriers limiting the uptake of nutrition services during pregnancy. In conclusion, the community would benefit from improved social behavior change communication on nutrition during pregnancy and multi-sectoral coordination among nutrition-specific and nutrition-sensitive sectors., Competing Interests: The authors declare that they have no competing interests.

The prevalence of stunting in Sub-Saharan Africa has changed little since 2000, and the number of stunted children has increased. In contrast, Ethiopia is an example where the national stunting prevalence and number of stunted children have decreased consistently. We compare regional differences and temporal patterns in stunting with large-scale program coverage to identify where and when programs may have led to reductions in stunting. Data from three national demographic and health surveys and population statistics illustrate, at the regional level, where and when the prevalence and number of stunted children changed since 2000. Reports from large-scale nutrition and health programs were used to identify ecologic associations between geographic program coverage and reductions in stunting. From 2000 to 2005, the decline in the national stunting prevalence was mainly a result of reductions in Oromiya, SNNP and Tigray. Few nutrition programs had high coverage during this time, and economic growth may have contributed to stunting reduction by increasing household wealth and investments in sanitation. From 2005 to 2011, declines in stunting prevalence in Amhara, SNNP, Somali and Oromiya were largely responsible for national reductions. Numerous programs were implemented at scale and could have plausibly improved stunting. While ecologic relationships suggest that economic growth and large-scale programs may have contributed to the reduction in stunting in Ethiopia, stunting did not decrease in all regions despite increased program coverage expansion of the health system. Additional impact evaluations are needed identify the most effective programs to accelerate the reduction in the prevalence and number of stunted children. © 2016 John Wiley & Sons Ltd., (© 2016 John Wiley & Sons Ltd.)

The incorporation of unnatural amino acids into proteins that act as spectroscopic probes can be used to study protein structure and function. One such probe is 4-cyanophenylalanine (PheCN), the nitrile group of which has a stretching mode that occurs in a region of the vibrational spectrum that does not contain any modes from the usual components of proteins and the wavenumber is sensitive to the polarity of its environment. In this work we evaluate the potential of UV resonance Raman spectroscopy for monitoring the sensitivity of the νC≡N band of PheCN incorporated into proteins to the protein environment. Measurement of the Raman excitation profile of PheCN showed that considerable resonance enhancement of the Raman signal was obtained using UV excitation and the best signal-to-noise ratios were obtained with excitation wavelengths of 229 and 244 nm. The detection limit for PheCN in proteins was ~10 μM, approximately a hundred-fold lower than the concentrations used in IR studies, which increases the potential applications of PheCN as a vibrational probe. The wavenumber of the PheCN νC≡N band was strongly dependent on the polarity of its environment, when the solvent was changed from H(2)O to THF it decreased by 8 cm(-1). The presence of liposomes caused a similar though smaller decrease in νC≡N for a peptide, mastoparan X, modified to contain PheCN. The selectivity and sensitivity of resonance Raman spectroscopy of PheCN mean that it can be a useful probe of intra- and intermolecular interactions in proteins and opens the door to its application in the study of protein dynamics using time-resolved resonance Raman spectroscopy.

Background: Iodine-deficiency disorders are a major public health problem in Ethiopia. In conjunction with implementing control programs, baseline information needs to be established., Objective: To investigate the distribution and degree of severity of iodine-deficiency disorders in terms of goiter prevalence, urinary iodine excretion (UIE) levels, and proportion of households with iodated salt in Ethiopia., Methods: A nationwide, community-based, cross-sectional study was conducted from February to May 2005 among 10,965 children aged 6 to 12 years. A multistage, proportional-to-population-size sampling method was used. Goiters were classified by the method recommended by the World Health Organization/UNICEF/International Council for the Control of Iodine Deficiency Disorders (WHO/UNICEF/ICCIDD), in which the thyroid gland is graded as 0 (normal), 1 (palpable goiter), or 2 (visible goiter); urinary iodine was determined by the wet digestion method; and salt samples were analyzed by a rapid test kit., Results: The national total goiter weighted prevalence rate among children aged 6 to 12 years was 39.9% (95% confidence interval, 38.6% to 41.2%), representing more than 4 million children. The median UIE was 2.45 microg/ dL; 45.8% of children had UIE values of 2 microg/dL or less, and 22.8% had UIE values of 2.01 to 5.0 pg/dL. Only 4.2% of the households had iodated salt., Conclusions: According to the WHO/UNICEF/ ICCIDD classification, both goiter prevalence and UIE levels indicate that the whole country appears to be severely affected by iodine deficiency. Furthermore, the virtual absence of iodated salt in the households shows that currently there is no salt iodization program in the country. Dietary sources of iodine in Ethiopia are not dependable, and hence a sustainable universal salt iodization program needs to be implemented without delay.

The alpha-helix is a ubiquitous structural element in proteins, and a number of studies have addressed the mechanism of helix formation and melting in simple peptides. However, fundamental issues remain to be resolved, particularly the temperature (T) dependence of the rate. In this work, we report application of a novel kHz repetition rate solid-state tunable NIR (pump) and deep UV Raman (probe) laser system to study the dynamics of helix unfolding in Ac-GSPEA3KA4KA4-CO-D-Arg-CONH2, a peptide designed for helix stabilization in aqueous solution. Its T-dependent UV resonance Raman (UVRR) spectra, excited at 197 nm for optimal enhancement of amide vibrations, were decomposed into variable contributions from helix and coil spectra. The helix fractions derived from the UVRR spectra and from far UV CD spectra were coincident at low T but deviated increasingly at high T, the UVRR curve giving higher helix content. This difference is consistent with the greater sensitivity of UVRR spectra to local conformation than CD. After a laser-induced T-jump, the UVRR-determined helix fractions defined monoexponential decays, with time-constants of approximately 120 ns, independent of the final T (Tf = 18-61 degrees C), provided the initial T (Ti) was held constant (6 degrees C). However, there was also a prompt loss of helicity, whose amplitude increased with increasing Tf, thereby defining an initial enthalpic phase, distinct from the subsequent entropic phase. These phases are attributed to disruption of H-bonds followed by reorientation of peptide links, as the chain is extended. When Ti was raised in parallel with Tf (10 degrees C T-jumps), the prompt phase merged into an accelerating slow phase, an effect attributable to the shifting distribution of initial helix lengths. Even greater acceleration with rising Ti has been reported in T-jump experiments monitored by IR and fluorescence spectroscopies. This difference is attributable to the longer range character of these probes, whose responses are therefore more strongly weighted toward the H-bond-breaking enthalpic process.

Metal-binding sites in metalloproteins frequently occur at the interfaces of elements of secondary structure, which has enabled the retrostructural analysis of natural proteins and the de novo design of helical bundles that bind metal ion cofactors. However, the design of metalloproteins containing beta-structure is less well developed, despite the frequent occurrence of beta-conformations in natural metalloproteins. Here, we describe the design and construction of a beta-protein, RM1, that forms a stable, redox-active 4-Cys thiolate Fe(II/III) site analogous to the active site of rubredoxin. The protein folds into a beta-structure in the presence and absence of metal ions and binds Fe(II/III) to form a redox-active site that is stable to repeated cycles of oxidation and reduction, even in an aerobic environment.

It is well-known that end caps and the peptide length can dramatically influence the thermodynamics of the helix-coil transition. However, their roles in determining the kinetics of the helix-coil transition have not been studied extensively and are less well understood. Kinetic Ising models and sequential kinetic models involving barrier crossing via diffusion all predict that the helix formation time depends monotonically on the peptide length with the relaxation time increasing with respect to increasing chain length. Here, we have studied the helix-coil transition kinetics of a series of Ala-based α -helical peptides of different length (19-39 residues), with and without end caps, using time-resolved infrared spectroscopy coupled with laser-induced temperature jump ( T -jump) initiation method. The helical content of these peptides was kinetically monitored by probing the amide carbonyl stretching frequencies (i.e., the amide I' band) of the peptide backbone. We found that the relaxation rates for peptides with efficient end caps are more rapid than those of the corresponding peptides without good end caps. These results indicate that efficient end-capping sequences can not only stabilize preexisting helices but also promote helix formation through initiation. Furthermore, we found that the relaxation times of these peptides, following a T -jump of 1-11 °C, show rather complex behaviors as a function of the peptide length, in disagreement with theoretical predications. Theses results are not readily explained by theories in which Ala is taken to have a single helical propensity ( s ). However, recent studies have suggested that s depends on chain length; when this factor is considered, the mean first-passage times of the coil-to-helix transition show similar dependence on the peptide length as those observed experimentally.

We studied here the binding of the mastoparan X peptide to a zwitterionic lipid bilayer (POPC) and demonstrated that nitrile-derivatized amino acids can be used to determine the hydration state (or change in hydration state) of specific sites of membrane-interactive peptides (upon binding). We have also shown that polarized ATR-FTIR measurements can further be used to uncover information regarding the spatial orientation of individual side chains as well as their conformational preference within the lipid bilayer.

It is well-known that the C=N stretching vibration in acetonitrile is sensitive to solvent. Therefore, we proposed in this contribution to use this vibrational mode to report local environment of a particular amino acid in proteins or local environmental changes upon binding or folding. We have studied the solvent-induced frequency shift of two nitrile-derivatized amino acids, which are, AlaCN and PheCN, in H(2)O and tetrahydrofuran (THF), respectively. Here, THF was used to approximate a protein's hydrophobic interior because of its low dielectric constant. As expected, the C=N stretching vibrations of both AlaCN and PheCN shift as much as approximately 10 cm(-1) toward higher frequency when THF was replaced with H2O, indicative of the sensitivity of this vibration to solvation. To further test the utility of nitrile-derivatized amino acids as probes of the environment within a peptide, we have studied the binding between calmodulin (CaM) and a peptide from the CaM binding domain of skeletal muscle myosin light chain kinase (MLCK(579-595)), which contains a single PheCN. MLCK(579-595) binds to CaM in a helical conformation. When the PheCN was substituted on the polar side of the helix, which was partially exposed to water, the C=N stretching vibration is similar to that of PheCN in water. In constrast, when PheCN is introduced at a site that becomes buried in the interior of the protein, the C=N stretch is similar to that of PheCN in THF. Together, these results suggest that the C=N stretching vibration of nitrile-derivatized amino acids can indeed be used as local internal environmental markers, especially for protein conformational studies.

The helix-coil transition kinetics of an alpha-helical peptide were investigated by time-resolved infrared spectroscopy coupled with laser-induced temperature-jump initiation method. Specific isotope labeling of the amide carbonyl groups with 13C at selected residues was used to obtain site-specific information. The relaxation kinetics following a temperature jump, obtained by probing the amide I' band of the peptide backbone, exhibit nonexponential behavior and are sensitive to both initial and final temperatures. These data are consistent with a conformation diffusion process on the folding energy landscape, in accord with a recent molecular dynamics simulation study.

The helix-coil transition of a synthetic alpha-helical peptide (the D-Arg peptide), Ac-YGG(KAAAA)(3)-CO-D-Arg-CONH(2), was studied by static far-UV circular dichroism (CD) and time-resolved infrared spectroscopy coupled with the laser-induced temperature-jump technique for rapid relaxation initiation. Equilibrium thermal unfolding measurements of the D-Arg peptide monitored by CD spectroscopy reveal an apparent two-state helix-coil transition, with a thermal melting temperature around 10 degrees C. Time-resolved infrared (IR) measurements following a laser-induced temperature jump, however, reveal biphasic (or multiphasic) relaxation kinetics. The fast phase rises within the 20 ns response time of the detection system. The slow phase has a decay lifetime of approximately 140 ns at 300 K and exhibits monotonic temperature dependence with an apparent activation energy around 15.5 kcal/mol.

Synthetic procedures have been developed which lead to the 2-aza congeners 3 and several related N-oxides 4. The analogues 3 exhibited a wide range of in vitro cytotoxicity against L1210 leukemia, the human colon adenocarcinoma cell line LoVo, and the doxorubicin resistant LoVo/DX cell line. Selected analogues of 3 showed significant P388 antileukemic activity in mice with 3c exhibiting high activity. This activity was also retained in the related N-oxide 4a. These heterocyclic bioisosteric models are representative of the first anthracene-9,10-diones which display antileukemic activity comparable to mitoxantrone.

We synthesized two chemically reactive A ring modified analogs of colchicine, 2-chloroacetyl-2-demethylthiocolchicine (2-CTC) and 3-chloroacetyl-3-demethylthiocolchicine (3-CTC). Both are similar to colchicine as inhibitors of tubulin polymerization and act as competitive inhibitors of colchicine binding (apparent Ki values, 3 microM). [14C]-labeled 2-CTC and 3-CTC bound to tubulin at 37 degrees C but not at 0 degree C, and bound drug formed covalent bond(s) with tubulin. The binding and covalent reactions were inhibited by podophyllotoxin. About 60% of the bound 3-CTC rapidly formed a covalent bond with tubulin. With 2-CTC the covalent reaction was slower than the binding reaction, and only one-third of the bound 2-CTC reacted covalently with tubulin. The ratio of radiolabel in beta-tubulin to that in alpha-tubulin was about 4:1 with both 2-CTC and 3-CTC.

A number of cytostatic compounds (2-4, 7, and 8), which can be described as "diaryl", inhibit tubulin polymerization, cause cells to accumulate in mitotic arrest, and competitively inhibit the binding of colchicine to tubulin. They differ, however, in the separation of the two aryl moieties. To attempt to understand this variability we prepared a series of analogues modeled on 3 and 4 ("benzodioxole series") and on 7 and 8 ("combretastatin series") which differed only in the number of methylene units (ranging from none to four) separating the aryl moieties. These compounds were evaluated for their effects on tubulin polymerization, colchicine binding, and the growth of L1210 murine leukemia cells. In terms of inhibitory effects on tubulin polymerization, for the combretastatin series there was an optimal separation of the two phenyl rings by a two-carbon bridge (compound 24), with progressively decreasing inhibitory activity when the separation was by one carbon (20), three carbons (25), or four carbons (28) (the biphenyl analogue 16 was inactive). The benzodioxole series, however, did not permit us to generalize this finding, because the least active agents prepared (39 and 40) had a two-carbon bridge, while those with one- (5 and 6) and three-carbon (46 and 47) bridges were nearly equivalent in potency. Submicromolar IC50 values for inhibition of L1210 cell growth were only obtained for compounds 20 (IC50, 0.2 microM), 24 (0.07 microM), and 25 (0.4 microM). While evaluating the effects of these agents on tubulin polymerization, we noted with the combretastatin series and with several standard agents that apparent potency (in terms of IC50 values) was always lower if the reaction was performed at 30 degrees C, with 0.25 mM MgCl2, than at 37 degrees C, with 1.0 mM MgCl2. This enhancement of IC50 values in the former system as compared with the latter was particularly dramatic for the less active agents (e.g., 28) as compared with the more active (e.g. 24).

The ipso bis displacements of fluoride from 1,4-difluoroanthracene-9,10-dione (3) and 1,4-difluoro-5,8-dihydroxyanthracene-9,10-dione (4) by excess of a diamine (or a monoamine) in pyridine at room temperature lead to the symmetrically substituted 1,4-bis-substituted analogues 5 and 6, respectively. The ipso monodisplacements of fluoride from 3 and 4 can be accomplished by treatment with less than 1 molar equiv of a diamine (or a monoamine) to yield 7 and 8, respectively. Treatment of 7 or 8 with a different diamine leads to the unsymmetrically substituted 1,4-bis[(aminoalkyl)amino]anthracene-9,10-diones 9 and 10, respectively. Many of the synthetic unsymmetrical analogues have been evaluated for their antitumor activity against L1210 in vitro and in vivo. Cross resistance of analogue 10a with mitoxantrone (2) and doxorubicin was evaluated against MDR lines in vitro against human colon carcinoma LOVO and its subline resistant to DOXO (LOVO/DOXO). Potential mechanisms for the observed cytotoxicity are presented and discussed.