Prevalance and determinants of hypertension among adults in Somalia using Somalia demographic health survey data, SDHS 2020.

BACKGROUND: Hypertension, a major global health concern, continues to affect millions of adults worldwide, leading to significant morbidity and mortality. The burden of hypertension is particularly pronounced in low- and middle-income countries, where limited healthcare resources and infrastructure pose unique challenges for effective prevention and management. Despite the pressing need for accurate data on hypertension prevalence and determinants, there is a dearth of research focusing on the Somali population. In this study, we aim to fill this critical knowledge gap by analyzing the latest available data from the Somalia Demographic Health Survey (SDHS) conducted in 2020. METHOD: The SDHS 2020 employed a three-stage stratified cluster sampling design to collect data from 48,796 individuals. Hypertension was measured through survey questions related to chronic diseases. Explanatory variables included age, sex, region, residence, tobacco use, wealth index, marital status, and body mass index (BMI). Statistical analysis involved univariate and multivariable logistic regression. RESULTS: The prevalence of hypertension in Somalia was found to be 2.11%, lower than previous studies in Hargeisa and the SLHDS 2020 report. Females had a higher prevalence than males, and urban areas exhibited higher rates compared to rural areas. Age, BMI, region, and wealth index were identified as significant factors associated with hypertension. DISCUSSION: The study's findings contribute to the understanding of hypertension in the Somali population and can inform public health interventions. The study benefits from its representative sample, multivariate analysis, and comparison with earlier studies. However, limitations include the cross-sectional design, limited information on lifestyle behaviors, and lack of data on treatment and control of hypertension. CONCLUSION: Hypertension is a public health concern in Somalia, and targeted interventions are needed to reduce its burden. Addressing factors such as age, gender, urban residence, BMI, and wealth index can contribute to hypertension management and control strategies. Future research should consider longitudinal studies and incorporate additional factors for a comprehensive assessment of hypertension etiology and management.

Occurrence, antibiotic resistance profiles and associated risk factors of Klebsiella pneumoniae in poultry farms in selected districts of Somalia Reginal State, Ethiopia.

BACKGROUND: Klebsiella pneumoniae is an opportunistic infection that causes production losses and death in the chicken industry. A cross-sectional study was conducted on exotic chicken breeds reared at the Jigjiga poultry farm from November 2022 to May 2023 to estimate the occurrence, associated risk factors, and antimicrobial susceptibility profiles of Klebsiella pneumoniae. The chickens were selected using systematic random sampling techniques. A total of 384 cloacal swabs were collected aseptically and transported to the laboratory for analysis. For statistical analysis, STATA® version 14.0 statistical software was used. RESULTS: From 384 examined faecal samples, 258 (67.2%) prevalences of Klebsiella pneumoniae were found. Furthermore, the association of the study's risk factors with the prevalence of Klebsiella pneumoniae was explored, and no statistically significant association was identified between sex and age. Nonetheless, relative prevalence at the age level was higher in chickens aged 12 months (67.6%) and Sasso breeds (90.0%). Similarly, male chickens and those raised for meat and egg production had a high prevalence rate of 72.5 and 75.8%, respectively. A total of 30 isolated Klebsiella pneumoniae colonies were tested in vitro for antibiotic sensitivity for six drugs, and it was shown that Klebsiella pneumoniae is moderately sensitive to Penicillin G (43.3%) while having higher resistance to Oxytetracycline (80.0%). CONCLUSIONS: The current findings revealed that the research area had the highest prevalence of Klebsiella pneumoniae, and the isolates were resistant to commonly used drugs in the study area. Thus, a long-term intervention plan, thorough research to determine a nationwide status, as well as further multi-drug resistance patterns and molecular characterization, were urged.

Assessment of the Performance of Lactate Dehydrogenase-Based Rapid Diagnostic Test for Malaria in Djibouti in 2022-2023.

Until 2020, Djiboutian health authorities relied on histidine-rich protein-2 (HRP2)-based rapid diagnostic tests (RDTs) to establish the diagnosis of Plasmodium falciparum. The rapid spread of P. falciparum histidine-rich protein-2 and -3 (pfhrp2/3) gene-deleted parasite strains in Djibouti has led the authorities to switch from HRP2-based RDTs to lactate dehydrogenase (LDH)-based RDTs targeting the plasmodial lactate dehydrogenase (pLDH) specific for P. falciparum and P. vivax (RapiGEN BIOCREDIT Malaria Ag Pf/Pv pLDH/pLDH) in 2021. This study was conducted with the primary objective of evaluating the diagnostic performance of this alternative RDT. Operational constraints related, in particular, to the implementation of this RDT during the COVID-19 pandemic were also considered. The performance of BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH) RDT was also compared to our previously published data on the performance of two HRP2-based RDTs deployed in Djibouti in 2018-2020. The diagnosis of 350 febrile patients with suspected malaria in Djibouti city was established using two batches of RapiGEN BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH) RDT over a two-year period (2022 and 2023) and confirmed by real-time quantitative polymerase chain reaction. The sensitivity and specificity for the detection of P. falciparum were 88.2% and 100%, respectively. For P. vivax, the sensitivity was 86.7% and the specificity was 100%. Re-training and closer supervision of the technicians between 2022 and 2023 have led to an increased sensitivity to detect P. falciparum (69.8% in 2022 versus 88.2% in 2023; p < 0.01). The receiver operating characteristic curve analysis highlighted a better performance in the diagnosis of P. falciparum with pLDH-based RDTs compared with previous HRP2-based RDTs. In Djibouti, where pfhrp2-deleted strains are rapidly gaining ground, LDH-based RDTs seem to be more suitable for diagnosing P. falciparum than HRP2-based RDTs. Awareness-raising and training for technical staff have also been beneficial.

Pattern of rheumatic heart disease among patients attending at a tertiary care hospital in Somalia: first report from Somalia.

Rheumatic heart disease (RHD) is the leading cause of valvular heart disease in underdeveloped nations. It remains a significant public health issue in Sub-Saharan African countries. This study aimed to determine the pattern, severity, and complications of RHD in Somalia. This was a retrospective cross-sectional study of all patients diagnosed with rheumatic heart disease. A total of 8526 echocardiographic examinations were done in our center over a two-year study period from January 2020 to December 2021. Patients with congenital cardiac disease, post-operative cases, myxomatous and old age degenerative disease were all excluded. Of 433 patients, 286 (66.1%) were female, and the mean age was 46.5 ± 20.3. The isolated mitral valve (MV) affected 222 (51.3%). Dual involvement of mitral and aortic valve (AV) was present in 190 (44%). Overall isolated or combined valve involvement, mitral regurgitation (MR) was the most common valve lesion 345 (79.7%), followed by mitral stenosis (MS) 160 (37%). According to the severity of lesions, severe MR was 230 (53.1%) patients, followed by severe MS (n=129, 29.8%). The most common complication of RHD depicted in our study were secondary pulmonary hypertension and enlarged left atrium, 23.8% (n=103) and 19.6% (n=85), respectively. In conclusion, in our study majority of RHD patients were females. Both isolated and in combination, MV was the most commonly affected, and mitral regurgitation was the most common valvular lesion. In our study high percentage of patients already had complications at the time of diagnosis.

Autoantibodies Which Bind to and Activate Keratinocytes in Systemic Sclerosis.

Systemic sclerosis (SSc) is a multisystem connective tissue disease characterised by pathological processes involving autoimmunity, vasculopathy and resultant extensive skin and organ fibrosis. Recent studies have demonstrated activation and aberrant wound healing responses in the epithelial layer of the skin in this disease, implicating the epithelial keratinocytes as a source of pro-fibrotic and inflammatory mediators. In this paper, we investigated the role of Immunoglobulin G (IgG) autoantibodies directed against epithelial cells, as potential initiators and propagators of pathological keratocyte activation and the ensuing SSc fibrotic cascade. A keratinocyte cell-based ELISA is used to evaluate the binding of SSc IgG. SSc skin biopsies were stained by immunofluorescence for the presence of IgG in the keratinocyte layer. Moreover, IgG purified from SSc sera was evaluated for the potential to activate keratinocytes in tissue culture and to induce TLR2 and 3 signalling in reporter cell lines. We demonstrate enhanced binding of SSc IgG to keratinocytes and the activation of these cells leading to the release of IL-1α, representing a potential initiating pathway in this disease.

Analysis of Echocardiographic Findings of Patients with Acute Ischemic Stroke Admitted to a Tertiary Care Hospital in Mogadishu, Somalia.

Background and Aims: The etiological investigation of the potential cardiac source of acute ischemic stroke is important for the secondary prevention of recurrent and future embolization. Transthoracic echocardiography is one of the most useful investigations for the assessment of the potential cardiac etiology of ischemic stroke. Our aim is to evaluate echocardiographic findings in patients with acute ischemic stroke admitted to a tertiary care hospital in Mogadishu, Somalia. Methods: This was a retrospective observational study conducted in the neurology department of a tertiary care hospital in Mogadishu, Somalia. We enrolled 315 patients with acute ischemic stroke admitted to the hospital who had undergone transthoracic echocardiography between March 2019 and March 2022. We analyzed transthoracic echocardiography findings, ischemic stroke subtypes, and their associated comorbidities. We also compared the demographic data, comorbidity, and survival status of patients with abnormal echo findings to those with normal echo findings. Findings: The mean age of patients was 62±12 years. Co-morbidities were present in about 251 (80%) of the subjects, hypertension was the most common comorbidity 99 (31.4%), followed by diabetes 72 (23%), and hyperlipidemia 37 (11.7%). Overall cardiac pathology in this study was 170 (54%). Forty-seven (15%) of the patients had low ejection fraction on transthoracic echocardiography. Male patients had slightly less left ventricular systolic dysfunction than female patients. 100 (32%) had left ventricular diastolic dysfunction (LVDD), while 113 (36%) had left ventricular hypertrophy (LVH). Patients with hypertension and diabetes had more echo abnormalities compared to others (P-values of 0.047 and 0.024, respectively). More abnormal echo findings were seen in patients who died during hospitalization than in those who survived (P = 0.008). Severe left ventricular systolic dysfunction was associated with higher mortality (P < 0.001). Conclusion: Most patients with stroke in this study had abnormal echocardiograms; however, only a few had cardioembolic strokes. Abnormalities in echocardiography were more common in patients who died during hospitalization than in those who survived.

Novel ANOVA-Statistic-Reduced Deep Fully Connected Neural Network for the Damage Grade Prediction of Post-Earthquake Buildings.

Earthquakes are cataclysmic events that can harm structures and human existence. The estimation of seismic damage to buildings remains a challenging task due to several environmental uncertainties. The damage grade categorization of a building takes a significant amount of time and work. The early analysis of the damage rate of concrete building structures is essential for addressing the need to repair and avoid accidents. With this motivation, an ANOVA-Statistic-Reduced Deep Fully Connected Neural Network (ASR-DFCNN) model is proposed that can grade damages accurately by considering significant damage features. A dataset containing 26 attributes from 762,106 damaged buildings was used for the model building. This work focused on analyzing the importance of feature selection and enhancing the accuracy of damage grade categorization. Initially, a dataset without primary feature selection was utilized for damage grade categorization using various machine learning (ML) classifiers, and the performance was recorded. Secondly, ANOVA was applied to the original dataset to eliminate the insignificant attributes for determining the damage grade. The selected features were subjected to 10-component principal component analysis (PCA) to scrutinize the top-ten-ranked significant features that contributed to grading the building damage. The 10-component ANOVA PCA-reduced (ASR) dataset was applied to the classifiers for damage grade prediction. The results showed that the Bagging classifier with the reduced dataset produced the greatest accuracy of 83% among all the classifiers considering an 80:20 ratio of data for the training and testing phases. To enhance the performance of prediction, a deep fully connected convolutional neural network (DFCNN) was implemented with a reduced dataset (ASR). The proposed ASR-DFCNN model was designed with the sequential keras model with four dense layers, with the first three dense layers fitted with the ReLU activation function and the final dense layer fitted with a tanh activation function with a dropout of 0.2. The ASR-DFCNN model was compiled with a NADAM optimizer with the weight decay of L2 regularization. The damage grade categorization performance of the ASR-DFCNN model was compared with that of other ML classifiers using precision, recall, F-Scores, and accuracy values. From the results, it is evident that the ASR-DFCNN model performance was better, with 98% accuracy.

Tripterygium wilfordii derivative celastrol, a YAP inhibitor, has antifibrotic effects in systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is characterised by extensive tissue fibrosis maintained by mechanotranductive/proadhesive signalling. Drugs targeting this pathway are therefore of likely therapeutic benefit. The mechanosensitive transcriptional co-activator, yes activated protein-1 (YAP1), is activated in SSc fibroblasts. The terpenoid celastrol is a YAP1 inhibitor; however, if celastrol can alleviate SSc fibrosis is unknown. Moreover, the cell niches required for skin fibrosis are unknown. METHODS: Human dermal fibroblasts from healthy individuals and patients with diffuse cutaneous SSc were treated with or without transforming growth factor ß1 (TGFß1), with or without celastrol. Mice were subjected to the bleomycin-induced model of skin SSc, in the presence or absence of celastrol. Fibrosis was assessed using RNA Sequencing, real-time PCR, spatial transcriptomic analyses, Western blot, ELISA and histological analyses. RESULTS: In dermal fibroblasts, celastrol impaired the ability of TGFß1 to induce an SSc-like pattern of gene expression, including that of cellular communication network factor 2, collagen I and TGFß1. Celastrol alleviated the persistent fibrotic phenotype of dermal fibroblasts cultured from lesions of SSc patients. In the bleomycin-induced model of skin SSc, increased expression of genes associated with reticular fibroblast and hippo/YAP clusters was observed; conversely, celastrol inhibited these bleomycin-induced changes and blocked nuclear localisation of YAP. CONCLUSIONS: Our data clarify niches within the skin activated in fibrosis and suggest that compounds, such as celastrol, that antagonise the YAP pathway may be potential treatments for SSc skin fibrosis.

Pattern of Neurological Disorders among Patients Evaluated in the Emergency Department; Cross-Sectional Study.

Introduction: Neurologic disorders are common reasons for emergency consultations. Most neurologic disorders seen in the emergency department (ED) are life-threatening and require urgent treatment. The goal of this study is to investigate the pattern of neurological disorders among patients evaluated in the ED. Methods: This is a cross-sectional study conducted in the ED of Mogadishu Somali Turkish Training and Research Hospital, from July 2021 to February 2022. The clinical and epidemiological characteristics of adult patients with neurologic manifestations in the ED were evaluated. Age, gender, distribution of neurological disease manifestations, neurological examination findings, and neurological diagnoses made by consultant neurologists were assessed. Results: During the study period, 321 patients were assessed (3.7 % of all ED admissions). The majority of the patients in the study were above 50 years of age (62.6% male). Hypertension was the most common comorbidity among these patients with 122 (38%) cases, followed by diabetes mellitus with 65 (20.2%), and heart diseases with 26 (8.1%) cases. The main reasons for neurology consultations were altered mental status with 141 (44%) cases, motor weakness with 102 (31.8%), seizures with 33 (10%), headache with 17 (5.3%), and vertigo with 9 (2.8%) cases. 196 (61%) had hemiplegia, 60 (18.7%) had consciousness impairment, and 38 (11.8%) had normal neurological examination. The most frequent neurological diagnoses were ischemic strokes with 125 (39%) cases, hemorrhagic strokes with 65 (20.2%), epileptic seizures with 28 (8.7%), and metabolic encephalopathies with 13 (4%) cases. The median duration of the neurology consultations was 20 minutes. 251 (78%) of the patients were admitted to the hospital, while 70 (22%) were discharged from the emergency department. After neurology consultation, the neurology department made the most admissions with 226 (90%) cases, while 25 (10%) were admitted by other departments. Of those admitted, 186 (74.2%) were admitted to the neurology ward, and 65 (25.8%) were admitted to the intensive care unit. Conclusion: In our study, neurologic emergencies accounted for 3.7% of all emergency admissions. Stroke, epileptic seizures, cerebral venous thrombosis, encephalopathies, and acute spinal cord diseases were the most common neurological disorders.  The admission rate was very high following neurologic assessment by neurologists.

Strategies to Reach Nomadic Children During Polio SIAs: Experience in Dadaab and Fafi Sub-Counties of Kenya after the 2013-2014 Polio Outbreak.

BACKGROUND: Poliomyelitis, often called polio is a viral paralytic disease caused by Polioviruses. Although all susceptible individuals are at risk of getting infected, only about 1% become paralyzed. During the 2013 Polio Outbreak in Garissa County in Kenya, 50% of the confirmed cases were from the nomadic population although it comprises of only less than 20% of the total population in the county. Following concerns from the Horn of Africa Polio Technical Advisory Group (TAG) regarding inadequate vaccine coverage of nomadic population, several strategies were put in place to improve coverage and Acute Flaccid Paralysis case reporting among nomads in the rest of the planned 2014 polio vaccination campaigns. We describe strategies initiated from April 2014 by the Ministry of Health and partners to reach children in nomadic settlement in the two sub-counties of Dadaab and Fafi of Garissa County. METHODS: The strategies involved improving the mapping and tracking of the nomadic population by establishing lists of nomadic settlements obtained from local clan leaders and government administrators, their <5-year-old populations and focal persons. Focal persons were used to mobilise residents in their respective settlements and guide vaccination teams during campaigns. Settlement leaders were sensitised to report cases of Acute Flaccid Paralysis. In remote hamlets, trained community health volunteers were used as vaccinators. In such places drugs for common illness were also provided during the campaigns. A tracking tool to monitor nomadic population movement and special tally sheets to capture data were created. Training of vaccination personnel and intense social mobilisation activities was done. RESULTS AND CONCLUSION: About 2,000 additional children, from both nomadic and non-nomadic areas were reached when the new initiatives were started. For the first time, an actual number of nomadic children accessed was documented. Suspected AFP cases continued to be reported from nomadic settlements, and the number of zero dose children among the nonpolio AFP cases dropped. With modification and improvement, these strategies may be used to take health services such as routine immunisation to nomadic communities and reduce their vulnerability to vaccine preventable disease outbreaks.

Combined exposure to hypoxia and ammonia aggravated biological effects on glucose metabolism, oxidative stress, inflammation and apoptosis in largemouth bass (Micropterus salmoides).

Hypoxia and ammonia are unavoidable environmental factors in aquaculture, and have been shown cause various adverse effects in fish. In the present study, a two-factor crossover experiment was carried out to evaluate the combined effect of hypoxia and ammonia on oxidative stress and glucose metabolism endpoints in largemouth bass. The fish were divided into four experimental groups: hypoxia and ammonia group, hypoxia group, ammonia group, and control group. The results showed that hypoxia and ammonia exposures both induced antioxidant response and oxidative stress (superoxide dismutase [SOD] and catalase [CAT] activities increased first then decreased, and malondialdehyde accumulated) and anaerobic glycolysis (increase of blood glucose, decrease of liver glycogen, accumulation of lactate, and increased lactate dehydrogenase activity). In addition, hypoxia and ammonia upregulated antioxidant enzyme genes (Cu/ZnSOD, CAT, and GPx), apoptosis genes (caspase 3, caspase 8, and caspase 9), as well as inflammatory genes (interleukin [IL]-1ß and IL-8) and downregulated an anti-inflammatory gene (IL-10), suggesting that apoptosis and inflammation may be related to oxidative stress. The increased expression of GLUT1, LDH, and MCT4 were induced by hypoxia and ammonia, suggesting that anaerobic glycolysis was increased. Furthermore, fish suffering from hypoxia or ammonia exposure showed some changes in gill tissues histology, and the most severe lesions of gill tissues appeared in simultaneous exposure. Overall, both hypoxia and ammonia affected homeostasis, and simultaneous exposure led to more deleterious effects on largemouth bass than exposure to the individual stressors.

Pathogenic Activation of Mesenchymal Stem Cells Is Induced by the Disease Microenvironment in Systemic Sclerosis.

OBJECTIVE: In systemic sclerosis (SSc), a persistent tissue repair process leads to progressive fibrosis of the skin and internal organs. The role of mesenchymal stem cells (MSCs), which characteristically initiate and regulate tissue repair, has not been fully evaluated. We undertook this study to investigate whether dividing metakaryotic MSCs are present in SSc skin and to examine whether exposure to the disease microenvironment activates MSCs and leads to transdifferentiation. METHODS: Skin biopsy material from patients with recent-onset diffuse SSc was examined by collagenase spread of 1-mm-thick surface-parallel sections, in order to identify dividing metakaryotic stem cells in each tissue plane. Adipose-derived MSCs from healthy controls were treated with dermal blister fluid (BF) from patients with diffuse SSc and profiled by next-generation sequencing, or they were evaluated for phenotypic changes relevant to SSc. Differential responses of dermal fibroblasts were studied in parallel. RESULTS: MSC-like cells undergoing active metakaryotic division were identified in SSc sections (but not control sections) most prominently in the deep dermis and adjacent to damaged microvessels, in both clinically involved and uninvolved skin. Furthermore, exposure to SSc BF caused selective MSC activation, inducing a myofibroblast signature, while reducing signatures of vascular repair and adipogenesis and enhancing migration and contractility. Microenvironmental factors implicated in inducing transdifferentiation included the profibrotic transforming growth factor ß, the presence of lactate, and mechanosensing, while the microenvironment Th2 cytokine, interleukin-31, enhanced osteogenic commitment (calcinosis). CONCLUSION: Dividing MSC-like cells are present in the SSc disease microenvironment where multiple factors, likely acting in concert, promote transdifferentiation and lead to a complex and resistant disease state.

Mogadishu calling: mental health awareness in Somalia via an innovative, live video-based mental health teaching programme established between Liverpool and Mogadishu.

In 2013 the Federal Government of Somalia contacted the Mersey Care National Health Service Foundation Trust (MCFT), asking whether they could formulate a teaching programme tailored towards improving mental health provision in Somalia, and the E-learning Mental Health Training Programme (SOM-Health) was eventually conceived. The fundamental aim was to provide mental health awareness to practitioners and trainees in Somalia so that they could deliver mental healthcare services confidently and effectively.

Prevalence and factors associated with neonatal mortality among neonates hospitalized at the National Hospital Nouakchott, Mauritania.

INTRODUCTION: Neonatal mortality remains a significant public health burden worldwide, with about 4 million deaths per year. To provide evidence for the implementation of prevention measures aimed at the reduction of neonatal mortality, we performed a study on factors associated with neonatal mortality at the Referral Hospital in Nouakchott, Mauritania. METHODS: We conducted a cross-sectional study between January 2013 and December 2013 and included neonatal patients hospitalized at the National Referral Hospital (NRH). Data were collected by reviewing the medical charts and through questionnaires administered to the parents. RESULTS: Two hundred and thirty-two (34.7%) of the 669 neonates included in the study died; 159 (71.3%) of deaths occurred during the first six days of life. Most neonates that died were born outside the hospital and admitted to NRH after birth (71.7%; 142/198). About 1/3 were transferred from other parts of the country outside of Nouakchott. Thirty (13.4%) of deaths were neonates born from teenage mothers. In bivariate analysis teenage mothers (RR=1.54; 95% CI: 1.15-2.05; p = 0.004), illiteracy of father (1.61; 1.13-23.0; p = 0.007), birth outside NRH (1.65; 1.28-2.13; p < 0.0001), low gestational age (3.28; 2.40-5.50; p < 0.0001), and low body temperature at admission (1.42; 1.11-1.83; p < 0.004) were significantly associated with neonatal death. In logistic regression analysis, low birth weight (adjusted odds ratio = 3.91; 95% confidence interval 1.69-9.05; p = 0.001), hypothermia (2.40; 1.12-5.14; p = 0.025), and birth outside the NRH (2.13; 1.02-4.45; p = 0.044) were independently associated with neonatal deaths. CONCLUSION: Neonatal mortality remains a significant burden in Mauritania. We identified different socioeconomic and clinical risk factors indicating the need for more intensified prenatal care and improved transport of high risk neonates, especially in the regions outside the capital.

Use of Patterned Collagen Coated Slides to Study Normal and Scleroderma Lung Fibroblast Migration.

Systemic sclerosis (SSc) is a spreading fibrotic disease affecting the skin and internal organs. We aimed to model pathogenic fibroblast migration in SSc in order to identify enhancing factors, measure the effect of migrating cells on underlying extracellular matrix (ECM) and test possible therapeutic inhibitors. Novel patterned collagen substrates were used to investigate alignment and migration of skin and lung fibroblasts from SSc patients and healthy controls. Normal lung but not skin fibroblasts consistently elongated and aligned with underlying collagen and migrated dependent on PDGF or serum. SSc lung fibroblasts remained growth factor dependent, did not migrate more rapidly and were less restricted to alignment of the collagen. Multiple collagen proline and lysine-modifying enzymes were identified in SSc but not control fibroblast extracellular matrix preparations, indicating differential levels of ECM modification by the diseased cells. Profiling of migrating cells revealed a possible SCF/c-Kit paracrine mechanism contributing to migration via a subpopulation of cells. Heparin, which binds ligands including PDGF and SCF, and imatininib which blocks downstream tyrosine kinase receptors, both inhibited lung fibroblast migration individually but showed synergy in SSc cells. Pathologic lung fibroblasts from SSc patients modify ECM during migration but remain growth factor dependent and sensitive to inhibitors.

A Role of Myocardin Related Transcription Factor-A (MRTF-A) in Scleroderma Related Fibrosis.

In scleroderma (systemic sclerosis, SSc), persistent activation of myofibroblast leads to severe skin and organ fibrosis resistant to therapy. Increased mechanical stiffness in the involved fibrotic tissues is a hallmark clinical feature and a cause of disabling symptoms. Myocardin Related Transcription Factor-A (MRTF-A) is a transcriptional co-activator that is sequestered in the cytoplasm and translocates to the nucleus under mechanical stress or growth factor stimulation. Our objective was to determine if MRTF-A is activated in the disease microenvironment to produce more extracellular matrix in progressive SSc. Immunohistochemistry studies demonstrate that nuclear translocation of MRTF-A in scleroderma tissues occurs in keratinocytes, endothelial cells, infiltrating inflammatory cells, and dermal fibroblasts, consistent with enhanced signaling in multiple cell lineages exposed to the stiff extracellular matrix. Inhibition of MRTF-A nuclear translocation or knockdown of MRTF-A synthesis abolishes the SSc myofibroblast enhanced basal contractility and synthesis of type I collagen and inhibits the matricellular profibrotic protein, connective tissue growth factor (CCN2/CTGF). In MRTF-A null mice, basal skin and lung stiffness was abnormally reduced and associated with altered fibrillar collagen. MRTF-A has a role in SSc fibrosis acting as a central regulator linking mechanical cues to adverse remodeling of the extracellular matrix.

An outbreak of acute febrile illness caused by Sandfly Fever Sicilian Virus in the Afar region of Ethiopia, 2011.

In malaria-endemic regions, many medical facilities have limited capacity to diagnose non-malarial etiologies of acute febrile illness (AFI). As a result, the etiology of AFI is seldom determined, although AFI remains a major cause of morbidity in developing countries. An outbreak of AFI was reported in the Afar region of Ethiopia in August of 2011. Retrospectively, 12,816 suspected AFI cases were identified by review of medical records. Symptoms were mild and self-limiting within 3 days after the date of onset; no fatalities were identified. All initial test results of AFI patient specimens were negative for selected pathogens using standard microbiological and molecular techniques. High-throughput sequencing of nucleic acid extracts of serum specimens from 29 AFI cases identified 17 (59%) of 29 samples as positive for Sandfly Fever Sicilian Virus (SFSV). These results were further confirmed by specific reverse transcription polymerase chain reaction. This is the first study implicating SFSV as an etiological agent for AFI in Ethiopia.

The space of access to primary mental health care: a qualitative case study.

Guided by theoretical perspectives of relational social science, this paper draws on reanalyses of multiple qualitative datasets related to a multi-ethnic, economically disadvantaged area in Liverpool, UK, with the aim to advance general understanding of access to primary mental health care while using local Somali minority as an instrumental focus. The findings generate a novel concept: the space of access. The shape and dynamics of the space of access are determined by at least four fields of tensions: understandings of area and community; cognitive mapping of mental well-being, illness and care; positioning of primary care services; and dynamics of resources beyond the 'medical zone' of care. The conclusions indicate a need for de-centring and re-connecting the role of medical professionals within primary care which itself needs to be transformed by endorsement of multiple avenues of access to diverse support and intrepid communication among all involved actors.