Search

This study, utilizing data from the 2020 Somaliland Demographic and Health Survey, investigates the prevalence of household solid fuel use in Somaliland and the factors associated with this practice. Our analysis reveals that a staggering 97.2% of households rely on solid fuels like wood and charcoal for cooking, with only 2.8% utilizing clean energy sources. We employed multilevel logistic regression to examine the influence of individual and community-level variables on fuel choice. Results highlight the significant roles of education level, gender of the household head, wealth status, and location of cooking in shaping fuel selection. The study, aligned with Sustainable Development Goal 7: Affordable and Clean Energy, emphasizes the urgency of promoting clean energy alternatives, improving cooking practices, and addressing the health and environmental impacts of solid fuel usage to foster a more sustainable energy landscape in Somaliland.

Abstract Background Seasonal malaria chemoprevention (SMC) using sulfadoxine-pyrimethamine plus amodiaquine (SP-AQ), is a community-based malaria preventive strategy commonly used in the Sahel region of sub-Saharan Africa. However, to date it has not been implemented in East Africa due to high SP resistance levels. This paper is a report on the implementation of SMC outside of the Sahel in an environment with a high level of presumed SP-resistance: five cycles of SMC using SPAQ were administered to children 3–59 months during a period of high malaria transmission (July–December 2019) in 21 villages in South Sudan. Methods A population-based SMC coverage survey was combined with a longitudinal time series analysis of health facility and community health data measured after each SMC cycle. SMC campaign effectiveness was assessed by Poisson model. SPAQ molecular resistance markers were additionally analysed from dried blood spots from malaria confirmed patients. Results Incidence of uncomplicated malaria was reduced from 6.6 per 100 to an average of 3.2 per 100 after SMC administration (mean reduction: 53%) and incidence of severe malaria showed a reduction from 21 per 10,000 before SMC campaign to a mean of 3.3 per 10,000 after each cycle (mean reduction: 84%) in the target group when compared to before the SMC campaign. The most prevalent molecular haplotype associated with SP resistance was the IRNGE haplotype (quintuple mutant, with 51I/59R/108N mutation in pfdhfr + 437G/540E in pfdhps). In contrast, there was a low frequency of AQ resistance markers and haplotypes resistant to both drugs combined (

Pfhrp2 and pfhrp3 gene deletions threaten the use of Plasmodium falciparum malaria rapid diagnostic tests globally. In South Sudan, deletion frequencies were 15.6% for pfhrp2, 20.0% for pfhrp3, and 7.5% for double deletions. Deletions were approximately twice as prevalent in monoclonal infections than in polyclonal infections.

BackgroundGhrelin (GHRL), a gastric peptide encoded by the GHRL gene, is known to be involved in energy homeostasis via its G protein receptor, encoded by the growth hormone secretagogue receptor (GHSR) gene. Some studies have shown associations between plasma GHRL levels and GHRL single-nucleotide polymorphisms (SNPs), namely the Leu72Met polymorphism (rs696217 TG), with type 2 diabetes mellitus (T2DM) and insulin resistance (IR), while others have not. The controversies in these associations raise the issue of ‘which SNPs in which populations.’ The aim of this study was to investigate whether SNPs in GHRL and/or GHSR genes were associated with T2DM, IR, or plasma GHRL levels among Arab Saudis.MethodsBlood was collected from 208 Saudi subjects with (n=107) and without (n=101) T2DM. DNA samples from these subjects were analyzed by real-time polymerase chain reaction to genotype five intronic SNPs in the GHRL (rs696217 TG, rs27647 CT, rs2075356 CT, and rs4684677 AT) and GHSR (rs509030 GC) genes. In addition, plasma GHRL levels were measured by a radioimmunoassay.ResultsNone of the SNPs were associated with T2DM, IR, or plasma GHRL levels. The frequencies of the alleles, genotypes, and haplotypes of the five SNPs were comparable between the T2DM patients and the non-diabetic subjects. A large number of the GHRL haplotypes indicates the molecular heterogeneity of the preproghrelin gene in this region.ConclusionNeither the Leu72Met polymorphism nor the other intronic GHRL and GHSR SNPs were associated with T2DM, IR, or GHRL levels. Further investigations should be carried out to explain the molecular basis of the association of the GHRL peptide with T2DM and IR.

BackgroundAlthough the exact mechanism of insulin resistance (IR) has not yet been established, IR is the hallmark characteristic of type 2 diabetes mellitus (T2DM). The aim of this study was to examine the relationship between plasma ghrelin levels and IR in Saudi subjects with T2DM.MethodsPatients with T2DM (n=107, cases) and non-diabetic apparently healthy subjects (n=101, controls) from Saudi Arabia were included in this study. The biochemical profiles and plasma insulin levels of all subjects were analyzed, and IR was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR) index. Active ghrelin levels in plasma were measured using the radioimmunoassay technique.ResultsOnly 46.7% (50 of 107) of the T2DM subjects had IR, including 26% (28 of 107) with severe IR (HOMA-IR ≥5), while 5.9% (six of 101) of the controls had moderate IR (3 ≤HOMA-IR

The role of the epithelial-to-mesenchymal transition (EMT) during hepatocellular carcinoma (HCC) progression is well established, however the regulatory mechanisms modulating this phenomenon remain unclear. Here, we demonstrate that transcription factor glioma-associated oncogene 1 (GLI1) modulates EMT through direct up-regulation of SNAI1 and serves as a downstream effector of the transforming growth factor-β1 (TGFβ1) pathway, a well-known regulator of EMT in cancer cells. Overexpression of GLI1 increased proliferation, viability, migration, invasion, and colony formation by HCC cells. Conversely, GLI1 knockdown led to a decrease in all the above-mentioned cancer-associated phenotypes in HCC cells. Further analysis of GLI1 regulated cellular functions showed that this transcription factor is able to induce EMT and identified SNAI1 as a transcriptional target of GLI1 mediating this cellular effect in HCC cells. Moreover, we demonstrated that an intact GLI1-SNAI1 axis is required by TGFβ1 to induce EMT in these cells. Together, these findings define a novel cellular mechanism regulated by GLI1, which controls the growth and EMT phenotype in HCC.

Background: Seasonal malaria chemoprevention (SMC) using sulfadoxine-pyrimethamine plus amodiaquine (SP-AQ), is a community-based malaria preventive strategy commonly used in the Sahel region of sub-Saharan Africa. However, to date it has not been implemented in East Africa due to high SP resistance levels. This paper is a report on the implementation of SMC outside of the Sahel in an environment with a high level of presumed SP-resistance: five cycles of SMC using SPAQ were administered to children 3–59 months during a period of high malaria transmission (July–December 2019) in 21 villages in South Sudan. Methods: A population-based SMC coverage survey was combined with a longitudinal time series analysis of health facility and community health data measured after each SMC cycle. SMC campaign effectiveness was assessed by Poisson model. SPAQ molecular resistance markers were additionally analysed from dried blood spots from malaria confirmed patients. Results: Incidence of uncomplicated malaria was reduced from 6.6 per 100 to an average of 3.2 per 100 after SMC administration (mean reduction: 53%) and incidence of severe malaria showed a reduction from 21 per 10,000 before SMC campaign to a mean of 3.3 per 10,000 after each cycle (mean reduction: 84%) in the target group when compared to before the SMC campaign. The most prevalent molecular haplotype associated with SP resistance was the IRNGE haplotype (quintuple mutant, with 51I/59R/108N mutation in pfdhfr + 437G/540E in pfdhps). In contrast, there was a low frequency of AQ resistance markers and haplotypes resistant to both drugs combined (< 2%). Conclusions: The SMC campaign was effective and could be used as an additional preventive tool in seasonal malaria settings outside of the Sahel, especially in areas where access to health care is unstable. Malaria case load reduction was observed despite the high level of resistance to SP. [ABSTRACT FROM AUTHOR]

Pfhrp2 and pfhrp3 gene deletions threaten the use of Plasmodium falciparum malaria rapid diagnostic tests globally. In South Sudan, deletion frequencies were 15.6% for pfhrp2, 20.0% for pfhrp3, and 7.5% for double deletions. Deletions were approximately twice as prevalent in monoclonal infections than in polyclonal infections. [ABSTRACT FROM AUTHOR]

Knockout of sulfatase 2 is associated with decreased steatohepatitis and fibrosis in a mouse model of nonalcoholic fatty liver disease. Am J Physiol Gastrointest Liver Physiol 319: G333-G344, 2020. First published July 20, 2020; doi:10.1152/ajpgi.00150.2019.--Sulfatase 2 (SULF2) is a heparan sulfate editing enzyme that regulates the milieu of growth factors and cytokines involved in a variety of cellular processes. We used a murine model of diet-induced steatohepatitis to assess the effect of SULF2 downregulation on the development of nonalcoholic steatohepatitis (NASH) and liver fibrosis. Wild-type B6;129 mice (WT) and Sulf2-knockout B6; 129P2-SULF2Gt(PST111)Byg mice (Sulf2-KO) were fed a fast-food diet (FFD) rich in saturated fats, cholesterol, and fructose or a standard chow diet (SC) ad libitum for 9 mo. WT mice on FFD showed a threefold increase in hepatic Sulf2 mRNA expression, and a 2.2-fold increase in hepatic SULF2 protein expression compared with WT mice on SC. Knockout of Sulf2 led to a significant decrease in diet-mediated weight gain and dyslipidemia compared with WT mice on FFD. Knockout of Sulf2 also abrogated diet-induced steatohepatitis and hepatic fibrosis compared with WT mice on FFD. Furthermore, expression levels of the profibrogenic receptors TGFR2 and PDGFR were significantly decreased in Sulf2-KO mice compared with WT mice on FFD. Together, our data suggest that knockout of Sulf2 significantly downregulates dyslipidemia, steatohepatitis, and hepatic fibrosis in a diet-induced mouse model of NAFLD, suggesting that targeting of SULF2 signaling may be a potential therapeutic mechanism in NASH. [ABSTRACT FROM AUTHOR]

Background: Ghrelin (GHRL), a gastric peptide encoded by the GHRL gene, is known to be involved in energy homeostasis via its G protein receptor, encoded by the growth hormone secretagogue receptor (GHSR) gene. Some studies have shown associations between plasma GHRL levels and GHRL single-nucleotide polymorphisms (SNPs), namely the Leu72Met polymorphism (rs696217 TG), with type 2 diabetes mellitus (T2DM) and insulin resistance (IR), while others have not. The controversies in these associations raise the issue of ‘which SNPs in which populations.’ The aim of this study was to investigate whether SNPs in GHRL and/or GHSR genes were associated with T2DM, IR, or plasma GHRL levels among Arab Saudis. Methods: Blood was collected from 208 Saudi subjects with (n=107) and without (n=101) T2DM. DNA samples from these subjects were analyzed by real-time polymerase chain reaction to genotype five intronic SNPs in the GHRL (rs696217 TG, rs27647 CT, rs2075356 CT, and rs4684677 AT) and GHSR (rs509030 GC) genes. In addition, plasma GHRL levels were measured by a radioimmunoassay. Results: None of the SNPs were associated with T2DM, IR, or plasma GHRL levels. The frequencies of the alleles, genotypes, and haplotypes of the five SNPs were comparable between the T2DM patients and the non-diabetic subjects. A large number of the GHRL haplotypes indicates the molecular heterogeneity of the preproghrelin gene in this region. Conclusion: Neither the Leu72Met polymorphism nor the other intronic GHRL and GHSR SNPs were associated with T2DM, IR, or GHRL levels. Further investigations should be carried out to explain the molecular basis of the association of the GHRL peptide with T2DM and IR. [ABSTRACT FROM AUTHOR]

Background: Although the exact mechanism of insulin resistance (IR) has not yet been established, IR is the hallmark characteristic of type 2 diabetes mellitus (T2DM). The aim of this study was to examine the relationship between plasma ghrelin levels and IR in Saudi subjects with T2DM. Methods: Patients with T2DM (n=107, cases) and non-diabetic apparently healthy subjects (n=101, controls) from Saudi Arabia were included in this study. The biochemical profiles and plasma insulin levels of all subjects were analyzed, and IR was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR) index. Active ghrelin levels in plasma were measured using the radioimmunoassay technique. Results: Only 46.7% (50 of 107) of the T2DM subjects had IR, including 26% (28 of 107) with severe IR (HOMA-IR ≥5), while 5.9% (six of 101) of the controls had moderate IR (3≤ HOMA-IR <5). HOMA-IR values were not associated with age, disease duration, or gender. Importantly, T2DM itself and the co-occurrence of IR with T2DM were significantly associated with low plasma ghrelin levels. However, ghrelin levels were inversely correlated with the HOMA-IR index, body weight, and fasting plasma insulin levels, mainly in the control subjects, which was indicative of the breakdown of metabolic homeostasis in T2DM. Conclusion: The prevalence of IR was relatively low, and IR may be inversely associated with plasma ghrelin levels among Saudi patients with T2DM. [ABSTRACT FROM AUTHOR]

The article offers information related to marginalization and rural development in Northern Kenya. Topics discussed include the impact of British colonization for the country, the presence of Somali inhabitants in Kenya, and the contribution of arid and semi-arid regions for economy. Also mentioned the role of the government for economic development.

Background: Sulfatase 2 (SULF2), an extracellular heparan sulphate 6-O-endosulphatase, has an oncogenic effect in hepatocellular carcinoma (HCC) that is partially mediated through glypican 3, which promotes heparin-binding growth factor signalling and HCC cell growth. SULF2 also increases phosphorylation of the anti-apoptotic Akt kinase substrate GSK3β and SULF2 expression is associated with a decreased apoptotic index in human HCCs. Methods: We investigated the functional and mechanistic effects of SULF2 on drug-induced apoptosis of HCC cells using immunohistochemistry, Western immunoblotting, gene transfection, real-time quantitative polymerase chain reaction, MTT and apoptosis assays and immunocytochemistry. Results: The increased expression of SULF2 in human HCCs was confirmed by immunohistochemistry and immunoblotting. Treatment with inhibitors of MEK, JNK and PI3 kinases decreased the viability of SULF2-negative Hep3B HCC cells and induced apoptotic caspase 3 and 7 activity, which was most strongly induced by the PI3K inhibitor LY294002. Forced expression of SULF2 in Hep3B cells significantly decreased activity of the apoptotic caspases 3 and 7 and induced resistance to LY294002-induced apoptosis. As expected, LY294002 inhibited activation of Akt kinase by PI3K. Conversely, knockdown of SULF2 using an shRNA construct targeting the SULF2 mRNA induced profound cell growth arrest and sensitized the endogenously SULF2-expressing HCC cell lines Huh7 and SNU182 to drug-induced apoptosis. The effects of knockdown of SULF2 on HCC cells were mediated by decreased Akt phosphorylation, downregulation of cyclin D1 and the anti-apoptotic molecule Bcl-2, and upregulation of the pro-apoptotic molecule BAD. Conclusion: The prosurvival, anti-apoptotic effect of SULF2 in HCC is mediated through activation of the PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

The article focuses on a study which showed that bone morphogenetic protein 3 (BMP3), EYA2, aristales-like homeobox-4 (ALX4) and vimentin genes are methylated in most colorectal neoplasms but rarely in normal epithelia. It evaluates high-yield methylated genes as candidate markers for screening colorectal neoplasia. It explores the effect of combining gene markers on detection sensitivity. It examines the relationship of BMP3, EYA2, ALX4 and vimentin genes.

Acute pulmonary embolism (PE), often resulting from deep vein thrombosis (DVT), is the third most frequent cause of cardiovascular death and is associated with increasing incidence, causing considerable morbidity and mortality. This review aims to evaluate the efficacy, safety, and outcomes of treatment options in the management of acute PE and DVT, encompassing both established and emerging technologies, such as catheter-directed thrombolysis, aspiration thrombectomy, and other endovascular techniques. A comprehensive literature review was conducted, assessing clinical studies, trials, and case reports that detail the use of percutaneous interventions for PE and DVT and analyzing the advantages and disadvantages of each percutaneous system. Several percutaneous treatments have shown promising results, especially in cases where rapid thrombus resolution is critical, such as in high- and intermediate-high-risk patients. The incidence of major complications, such as bleeding, remains a consideration, though it is generally manageable with proper patient selection and technique. It is fundamentally important to tailor the specific treatment strategy to the clinical and anatomical characteristics of each patient. Percutaneous treatments for acute PE and DVT represent valuable options in the therapeutic arsenal, offering enhanced outcomes in appropriately selected patients. Ongoing advancements in technology and technique, along with comprehensive clinical trials, are essential to further define the role and optimize the use of these interventions.

Coronary artery calcification is a complex anatomical and histological pathology with different pathways that contribute to calcium deposit and calcification progression. As part of the atherosclerotic process, extensive calcifications are becoming more common and are associated with poorer PCI outcomes if not properly addressed. Since no drug has shown to be effective in changing this process once it is started, proper knowledge of the underlying pathogenesis and how to diagnose and manage it is essential in contemporary coronary intervention. Atherosclerosis is a pandemic disease, quickly spreading across the world and not limited anymore to the industrialized Western world. In this paper, we review the role of intracoronary imaging and the main technologies available and propose a simple and rational algorithm for the choice of a preferential first strategy in the treatment of severely calcified coronary atherosclerosis, followed by three emblematic cases on how we successively applied it.

Safe and hygienic management of human waste is essential in humanitarian settings. Urine-diverting dry toilets (UDDTs) can enable this management in some humanitarian emergency settings. A seeded, longitudinal environmental study was conducted in Hiloweyn refugee camp, Dollo Ado, Ethiopia, to measure Escherichia coli and Ascaris suum ova inactivation within closed UDDT vaults and to document environmental conditions (temperature, moisture content, and pH) that could influence inactivation. Hiloweyn camp represented an optimal location for a desiccation-based sanitation technology such as the UDDT. E. coli and Ascaris ova inactivation was observed in UDDTs under warm, dry, alkaline conditions at 6, 9, and 12 months of storage; UDDTs with samples containing <1000 E. coli/g total solids increased from 30 % to 95 % over 12 months, and a >2.8-log 10 reduction in Ascaris ova viability was observed after 6 months. Additional laboratory-based studies were conducted to provide insights into the field study findings and study the impact of hydrated lime on E. coli and Ascaris ova inactivation. Results suggest that adding hydrated lime to elevate pH > 12 may increase inactivation and decrease storage time. Overall, UDDTs could contribute to the safe and hygienic management of human waste in comparable warm and dry humanitarian settings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Thomas Handzel reports financial support was provided by Research for Health in Humanitarian Crises. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Background: The underlying mechanisms responsible for the clinical benefits following coronary sinus narrowing and pressure elevation remain unclear. The present study aims to investigate whether coronary sinus narrowing improves the indexes of coronary microcirculatory function., Methods: Patients with refractory angina who had a clinical indication for reducer implantation underwent invasive physiological assessments before and 4 months after the procedure. The primary outcome was the change in the values of the index of microcirculatory resistance. Secondary end points included changes in coronary flow reserve and the resistive resistance ratio values. Angina status was assessed with the Canadian Cardiology Society class and the Seattle Angina Questionnaire., Results: Twenty-four patients with a history of obstructive coronary artery disease and prior coronary revascularization (surgical and percutaneous) treated with reducer implantation were enrolled, and 21 of them (87%) underwent repeated invasive coronary physiological assessment after 4 months. The index of microcirculatory resistance values decreased from 33.35±19.88 at baseline to 15.42±11.36 at 4-month follow-up ( P <0.001; mean difference, -17.90 [95% CI, -26.16 to -9.64]). A significant (≥20% from baseline) reduction of the index of microcirculatory resistance was observed in 15 (71.4% [95% CI, 47.8%-88.7%]) patients. The number of patients with abnormal index of microcirculatory resistance (≥25) decreased from 12 (57%) to 4 (19%; P =0.016). Coronary flow reserve increased from 2.46±1.52 to 4.20±2.52 (mean difference, 1.73 [95% CI, 0.51-2.96]). Similar findings were observed for resistive resistance ratio values. Overall, 16 patients (76.1%) had an improvement of 1 Canadian Cardiology Society class. Seattle Angina Questionnaire summary score increase of around 3 points (3.01 [95% CI, 1.39-4.61])., Conclusions: Coronary sinus reduction implantation is associated with a significant improvement in the parameters of coronary microcirculatory function. These findings provide insights into the improvement of angina symptoms and may have implications for the treatment of coronary microvascular dysfunction., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05174572., Competing Interests: Disclosures Dr Campo received research grants from SMT, Eukon, Siemens, GE Healthcare, and Abbott Vascular outside the present work. Dr Biscaglia received research grants from SMT, Eukon, Siemens, GE Healthcare, and Abbott Vascular outside the present work. Dr Banai is the medical director of Neovasc, Inc. The other authors report no conflicts.

Background: Atrial fibrillation catheter ablation (AFCA) should be considered as a strategy to avoid pacemaker (PM) implantation for patients with bradycardia-tachycardia syndrome (BTS), but lack of evidence is remarkable., Methods: Our aim was to conduct a random-effects model meta-analysis on safety and efficacy data from controlled trials and observational studies. We compared atrial fibrillation (AF) recurrence, AF progression, procedural complication, additional procedure, cardiovascular death, cardiovascular hospitalization, heart failure and stroke in patients undergoing AFCA vs. PM implantation., Results: PubMed/MEDLINE, Cochrane Database and Google Scholar were screened, and four retrospective studies were selected. A total of 776 patients (371 in the AFCA group, 405 in the PM group) were included. After a median follow-up of 67.5 months, lower AF recurrence [odds ratio (OR) 0.06, confidence interval (CI) 0.02-0.18, I2 = 82.42%, P < 0.001], AF progression (OR 0.12, CI 0.06-0.26, I2 = 0%, P < 0.001), heart failure (OR 0.12, CI 0.04-0.34, I2 = 0%, P < 0.001), and stroke (OR 0.30, CI 0.15-0.61, I2 = 0%, P = 0.001) were observed in the AFCA group. No differences were observed in cardiovascular death and hospitalization (OR 0.48, CI 0.10-2.28, I2 = 0%, P = 0.358 and OR 0.43, CI 0.14-1.29, I2 = 87.52%, P = 0.134, respectively). Higher need for additional procedures in the AFCA group was highlighted (OR 3.65, CI 1.51-8.84, I2 = 53.75%, P < 0.001). PM implantation was avoided in 91% of BTS patients undergoing AFCA., Conclusions: AFCA in BTS patients seems to be more effective than PM implantation in reducing AF recurrence and PM implantation may be waived in most BTS patients treated by AFCA. Need for additional procedures in AFCA patients is balanced by long-term benefit in clinical end points., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are known risk factors for liver disease, cirrhosis and hepatocellular carcinoma (HCC). There is substantial global variation in HBV and HCV prevalence resulting in variations in cirrhosis and HCC. We previously reported high prevalence of HBV and HCV infections in Somali immigrants seen at an academic medical center in Minnesota., Aim: To determine the prevalence of chronic viral hepatitis in Somali immigrants in Minnesota through a community-based screening program., Methods: We conducted a prospective community-based participatory research study in the Somali community in Minnesota in partnership with community advisory boards, community clinics and local mosques between November 2010 and December 2015 (data was analyzed in 2020). Serum was tested for hepatitis B surface antigen, hepatitis B core antibody, hepatitis B surface antibody and anti-HCV antibody., Results: Of 779 participants, 15.4% tested positive for chronic HBV infection, 50.2% for prior exposure to HBV and 7.6% for chronic HCV infection. Calculated age-adjusted frequencies in males and females for chronic HBV were 12.5% and 11.6%; for prior exposure to HBV were 44.8% and 41.3%; and for chronic HCV were 6.7% and 5.7%, respectively. Seven participants developed incident HCC during follow up., Conclusion: Chronic HBV and HCV are major risk factors for liver disease and HCC among Somali immigrants, with prevalence of both infections substantially higher than in the general United States population. Community-based screening is essential for identifying and providing health education and linkage to care for diagnosed patients., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Given the increasing frequency and duration of humanitarian emergencies worldwide, there is a need to identify a greater range of effective and contextually appropriate water, sanitation and hygiene (WASH) interventions. Typical sanitation systems may be poorly suited for some of the conditions in which humanitarian emergencies can occur, such as in drought-prone regions. Urine-diversion dry toilets (UDDTs) are one potential alternative sanitation option which can be used in these conditions. Between 2014 and 2016, the U.S. Centers for Disease Control and Prevention (CDC) partnered with local agencies to evaluate the acceptability of UDDTs in a refugee camp in Ethiopia. The overall goals were to provide evidence regarding the level of adoption and satisfaction with UDDTs in this emergency context and the factors associated with satisfaction. Two cross-sectional surveys were conducted 18-months apart, using a stratified design to sample UDDT and latrine users for comparison. The proportion who reported to use their UDDT consistently was 88.8% (95% CI 85.1-92.5) in the first survey and 93.4% (95% CI 90.6-96.2) in the second survey. Reported satisfaction levels were significantly higher among respondents in the second survey (p < 0.0001), where 97.0% (95% CI 95.1-98.9) of respondents stated either that they were mostly or very satisfied with their UDDT. There was no significant difference detected in satisfaction between UDDT and latrine users (p = 0.28). Using a multivariable logistic regression model, we identified several factors associated with a higher level of satisfaction with UDDTs. Those who had previously (before coming to the camp) used a pit latrine (AOR = 4.2; 95% CI 1.4-12.7) or had no sanitation system (AOR = 2.4; 95% CI 1.3-4.4) relative to a pour-flush toilet, had a clean UDDT (AOR = 2.8; 95% CI 1.7-4.6), had been in the camp for a longer time period (AOR = 2.3; 95% CI 1.7-3.0), did not share their UDDT (AOR = 1.8; 95% CI 1.0-3.0) and had used their UDDT for a longer time period (AOR = 1.7; 95% CI 1.2-2.4) had higher odds of satisfaction. The findings demonstrate that UDDTs have been effectively introduced and utilized in this context and this may have implications for other humanitarian settings where they can be similarly managed., (Published by Elsevier GmbH.)

Background: The optimal approach to guide percutaneous coronary intervention (PCI) has yet to be defined. The aim of this study was to compare functional driven (fractional flow reserve) versus intravascular imaging (intravascular ultrasound, IVUS, and/or optical coherence tomography, OCT) versus standard (coronary angiography only, CA)-guided PCI., Methods: Randomized controlled trials (RCTs) and propensity score weight-matched studies (PSWMs) comparing FFR versus IVUS versus OCT versus CA-guided PCI were included. Major adverse cardiovascular event (MACE; a composite end point of death or myocardial infarction [MI] or revascularization) was the primary endpoint, whereas definite stent thrombosis (ST) and single components of MACE were the secondary ones. Primary analyses were performed including only RCTs, secondary also with PSWMs., Results: Thirty-three studies were included in the analysis, 16 RCTs and 17 PSWMs. After 2 (1-3) years, IVUS performed better for MACE than CA (odds ratio [OR] 0.75 0.52-0.88), whereas there was just a trend for FFR (OR 0.81, 0.64-1.02). These results were mainly driven by reduced risk of all cause death, MI (FFR OR 0.74:0.57-0.99 and IVUS OR 0.82:0.54-0.94) and revascularization. IVUS reduced ST while FFR did not, and at meta-regression analysis, there was a trend for superiority of IVUS versus FFR to reduce subsequent MI in acute coronary syndrome (ACS) patients. The present results were consistent also after adding studies with PSWMs., Conclusions: Functional and intravascular imaging approaches seem to perform similarly in term of clinical outcomes, while both performed better compared with the standard approach. Imaging showed a potential benefit for ACS patients. The present results stress the need for a wider use of functional or imaging driven PCI., (© 2019 Wiley Periodicals, Inc.)

Incidence and predictors of adverse events after dual antiplatelet therapy (DAPT) cessation in patients treated with thin stents (<100 microns) in unprotected left main (ULM) or coronary bifurcation remain undefined. All consecutive patients presenting with a critical lesion of an ULM or involving a main coronary bifurcation who were treated with very thin strut stents were included. MACE (a composite end point of cardiovascular death, myocardial infarction [MI], target lesion revascularization [TLR], and stent thrombosis [ST]) was the primary endpoint, whereas target vessel revascularization (TVR) was the secondary endpoint, with particular attention to type and occurrence of ST and occurrence of ST, CV death, and MI during DAPT or after DAPT discontinuation. All analyses were performed according to length of DAPT dividing the patients in 3 groups: Short DAPT (3-months), intermediate DAPT (3 to 12 months), and long DAPT (12-months). A total of 117 patients were discharged with an indication for DAPT ≤3 months (median 1: 1 to 2.5), 200 for DAPT between 3 and 12 months (median 8: 7 to 10), and 1,958 with 12 months DAPT. After 12.8 months (8 to 20), MACE was significantly higher in the 3-month group compared with 3 to 12 and 12-month groups (9.4% vs 4.0% vs 7.2%, p ≤0.001), mainly driven by MI (4.4% vs 1.5% vs 3%, p ≤0.001) and overall ST (4.3% vs 1.5% vs 1.8%, p ≤0.001). Independent predictors of MACE were low GFR and a 2 stent strategy. Independent predictors of ST were DAPT duration <3 months and the use of a 2-stent strategy. In conclusion, even stents with very thin strut when implanted in real-life ULM or coronary bifurcation patients discharged with short DAPT have a relevant risk of ST, which remains high although not significant after DAPT cessation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Percutaneous coronary intervention (PCI) of unprotected left main disease (ULM) with drug-eluting stents (DES) is hampered by lack of information on long-term (≥10 years) safety data. All patients treated with PCI on ULM in 9 international centers with at least 10 years follow-up were enrolled. Baseline and procedural features were recorded. Repeat PCI (re-PCI) on ULM at 10 years was the primary end point. Secondary end points included major adverse cardiac events and its components (cardiac and noncardiac death, myocardial infarction, re-PCI not on ULM, and stent thrombosis). Sensitivity analysis was performed according to the presence of isolated ULM disease: 284 patients were enrolled. A total of 70 patients (21%) performed a re-PCI on ULM, 39 in the first year, and 31 between 1 and 10 years (only 5 overall performed for acute coronary syndrome). Patients with re-PCI on ULM did not show differences in baseline and procedural features, or experience higher rates of cardiovascular death (12% vs 11%, p 0.65), myocardial infarction (11% vs 6%, p 0.56), or of re-PCI on non-ULM disease (31% vs 27%, p 0.76) compared with those without re-PCI on ULM. At Kaplan-Meier analysis, patients with PCI in other coronary vessels were at higher risk of major adverse cardiac events, driven by target vessel revascularization (20.4% vs 32.9%, p 0.009), as confirmed at multivariate analysis (stenosis other than LM; hazard ratio 2, 1.4 to 2.7, all CI 95%). In conclusion, despite of using first-generation stents, PCI on ULM is safe, with low rates of recurrent events due to index revascularization. Progression of atherosclerotic lesions on other coronary vessels represents the only independent predictive factor for prognosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: There is uncertainty on which stenting approach confers the best long-term outlook for unprotected left main (ULM) bifurcation disease., Methods and Results: This is a non-randomized, retrospective study including all consecutive patients with 50% stenosis of the left main involving at least 1 of the arteries stemming from the left main treated with drug-eluting stents (DES) in 9 European centers between 2002 and 2004. Patients were divided into two groups: those treated with provisional stentings vs. those treated with two stent strategy. The outcomes of interest were 10-year rates of target lesion revascularization (TLR), major adverse cardiac events (MACE), and their components (cardiovascular death, myocardial infarction [MI], or repeat revascularization), along with stent thrombosis (ST). A total of 285 patients were included, 178 (62.5%) in the provisional stenting group and 87 (37.5%) in the two stent group. After 10 years, no differences in TLR were found at unadjusted analysis (19% vs 25%, p>0.05) nor after propensity score matching (25% vs 28%, p>0.05). Similar rates of MACE (60% vs 66%, p>0.05), death (34% vs 43%, p>0.05), MI (9% vs 14%, p>0.05) and ST were also disclosed at propensity-based analysis., Conclusion: Even after 10 year follow-up, patients treated with provisional stenting on left main showed comparable rates of target lesion revascularization compared to two stent strategy., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Although cholangiocarcinoma (CC) is an uncommon and highly lethal malignancy, early detection enables the application of potentially curative therapies and improves survival. Consequently, tools to improve the early diagnosis of CC are urgently needed. During a screen for genes epigenetically suppressed by methylation in CC that might serve as methylation markers for CC, we found that the BMP3 gene is methylated in CC cell lines, but the potential diagnostic value and the function of BMP3 in CC are unknown., Methods: We aimed to quantitatively assess BMP3 methylation in resected CC tumor specimens using methylation specific PCR and evaluate the tumor suppressor role of BMP3 in biliary cancer cell lines in comparison to an immortalized normal cholangiocyte cell line. Expression of BMP3 was quantified by mRNA levels before and after treatment with 5-Aza-2'-deoxycytidine and trichostatin A. After transfection with a BMP3 -containing plasmid, cell viability was measured using the bromodeoxyuridine incorporation assay and apoptosis quantified by caspase assay., Results: In primary CC tumor tissue specimens significantly more methylated BMP3 copies were found when compared to matched benign bile duct epithelium from the same patient, with high specificity. BMP3 expression was absent in cell lines with BMP3 methylation; this suppression of BMP3 expression was reversed by treatment with a DNA demethylating agent and histone de-acetylase inhibitor. Transfection of a BMP3 -expressing construct into a BMP3 -negative biliary cancer cell line restored BMP3 mRNA expression and reduced cell proliferation and cell viability while increasing the rate of apoptosis., Conclusion: These findings strongly support a tumor suppressor role for BMP3 in CC and suggest that BMP3 methylation may be a new biomarker for early detection of CCs. of the peptidome are also involved.

Discriminant markers are required for accurate cancer screening. We evaluated genes frequently methylated in colorectal neoplasia to identify the most discriminant ones. Four genes specifically methylated in colorectal cancer [bone morphogenetic protein 3 (BMP3), EYA2, aristaless-like homeobox-4 (ALX4), and vimentin] were selected from 41 candidate genes and evaluated on 74 cancers, 62 adenomas, and 70 normal epithelia. Methylation status was analyzed qualitatively and quantitatively and confirmed by bisulfite genomic sequencing. Effect of methylation on gene expression was evaluated in five colon cancer cell lines. K-ras and BRAF mutations were detected by sequencing. Methylation of BMP3, EYA2, ALX4, or vimentin was detected respectively in 66%, 66%, 68%, and 72% of cancers; 74%, 48%, 89%, and 84% of adenomas; and 7%, 5%, 11%, and 11% of normal epithelia (P < 0.01, cancer or adenoma versus normal). Based on area under the curve analyses, discrimination was not significantly improved by combining markers. Comethylation was frequent (two genes or more in 72% of cancers and 84% of adenomas), associated with proximal neoplasm site (P < 0.001), and linked with both BRAF and K-ras mutations (P < 0.01). Cell line experiments supported silencing of expression by methylation in all four study genes. This study shows BMP3, EYA2, ALX4, and vimentin genes are methylated in most colorectal neoplasms but rarely in normal epithelia. Comethylation of these genes is common, and pursuit of complementary markers for methylation-negative neoplasms is a rational strategy to optimize screening sensitivity.