Non-Motor Symptoms and Associated Factors in Parkinson’s Disease Patients in Addis Ababa, Ethiopia: A Multicenter Cross-Sectional Study

BACKGROUND: Non-motor symptoms (NMSs) of Parkinson’s disease (PD) were often overlooked and less studied. Little is known about NMSs in Ethiopia. The aim of the study was to determine the prevalence of NMSs and associated factors.METHODS: A multi-center cross-sectional observational study was conducted. NMS questionnaire was used to screen for the NMSs. Both descriptive and analytical statistics were used to analyze the data.RESULTS: Total of 123 PD patients with median of 4 years were investigated. The mean age of PD patients was 62.9 years. The mean age of PD onset was 58.3 years. In 23.6% the age of onset was below age 50. Males accounted 72.4%. Majority of the patients were on Levodopa alone and 31.7% were on levodopa plus trihexyphenidyl. Longer duration of illness was associated with frequent occurrence of NMSs. Constipation was the commonest NMS (78%), followed by urinary urgency (67.5%) and nocturia (63.4%). An unexplained pain was reported by 45.5%, cognitive impairment (45.5%), and sleep disturbance was reported by 45.5% of the study participants. Neurophysciatric symptoms were reported by small proportion of the patients. Lower monthly earning was associated with swallowing problem, unexplained weight change, and lighheadness.CONCLUSION: The prevalence of NMS was high among PD patients in Ethiopia. Constipation was the commonest NMS. Longer duration of illness was associated with frequent occurrence of NMSs. Lower monthly earning was associated with swallowing problem, unexplained weight change, and lighheadness

Seroprevalence of SARS-CoV-2 antibody among individuals aged above 15 years and residing in congregate settings in Dire Dawa city administration, Ethiopia

Background Determining the extent of seropositivity of SARS-CoV-2 antibody has the potential to guide prevention and control efforts. We aimed to determine the seroprevalence of SARS-CoV-2 antibody among individuals aged above15 years and residing in the congregate settings of Dire Dawa city administration, Ethiopia. Method We analyzed COVID-19 seroprevalence data on 684 individuals from a community based cross-sectional survey conducted among individuals aged above 15 years and residing in congregate settings in Dire Dawa from June 15 to July 30, 2020. Data were collected using interview and blood sample collection. Participants were asked about demographic characteristics, COVID-19 symptoms, and their practice of preventive measures. Seroprevalence was determined using SARS-CoV-2 IgG test. Bivariate and multivariate multilevel mixed effects logistic regression model was fitted and statistical significance was set at p value < 0.05. Result The estimated SARS-CoV-2 seroprevalence was 3.2% (95 % CI 2.0–4.8) in the study region with no differences by age and sex but considerable differences were observed by self-reported practice of COVID-19 preventive measures. The cluster effect is not significant (P = 0.396) which has suggested no evidence of heterogeneity in SARS-CoV-2 seroprevalence among the clusters. The odds of SARS-CoV-2 antibody seroprevalence were higher for individuals who were employed and work by moving from home to work area (AOR; 9.73 95% CI 2.51, 37.68), reported of not wearing facemasks when leaving home (AOR; 6.4 95% CI 2.30, 17.66) and did not practice physical distancing measures (AOR; 10 95% CI 3.01, 33.20) compared to their counterparts, respectively. Our estimated seroprevalence of SARS-CoV-2 among participants who reported not to have practiced social distancing measures was 12.8 (95% CI, 7.0, 19) and 1.5 (95% CI, 0.5, 2.5) among those who reported of practicing them. More than 80% of study participants reported of implementing infection prevention measures (face masks and physical distancing recommendations). Conclusion The detected SARS-CoV-2 seroprevalence among the study participants was low at the time of the survey indicating higher proportion of population yet to be infected. COVID-19 preventive measures were associated with reduced seroprevalence and should be promoted to avoid transmission to the uninfected majority

Role of Sphingomyelin Synthase in Controlling the Antimicrobial Activity of Neutrophils against Cryptococcus neoformans

The key host cellular pathway(s) necessary to control the infection caused by inhalation of the environmental fungal pathogen Cryptococcus neoformans are still largely unknown. Here we have identified that the sphingolipid pathway in neutrophils is required for them to exert their killing activity on the fungus. In particular, using both pharmacological and genetic approaches, we show that inhibition of sphingomyelin synthase (SMS) activity profoundly impairs the killing ability of neutrophils by preventing the extracellular release of an antifungal factor(s). We next found that inhibition of protein kinase D (PKD), which controls vesicular sorting and secretion and is regulated by diacylglycerol (DAG) produced by SMS, totally blocks the extracellular killing activity of neutrophils against C. neoformans. The expression of SMS genes, SMS activity and the levels of the lipids regulated by SMS (namely sphingomyelin (SM) and DAG) are up-regulated during neutrophil differentiation. Finally, tissue imaging of lungs infected with C. neoformans using matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS), revealed that specific SM species are associated with neutrophil infiltration at the site of the infection. This study establishes a key role for SMS in the regulation of the killing activity of neutrophils against C. neoformans through a DAG-PKD dependent mechanism, and provides, for the first time, new insights into the protective role of host sphingolipids against a fungal infection

Sphingomyelin Synthases Regulate Protein Trafficking and Secretion

Sphingomyelin synthases (SMS1 and 2) represent a class of enzymes that transfer a phosphocholine moiety from phosphatidylcholine onto ceramide thus producing sphingomyelin and diacylglycerol (DAG). SMS1 localizes at the Golgi while SMS2 localizes both at the Golgi and the plasma membrane. Previous studies from our laboratory showed that modulation of SMS1 and, to a lesser extent, of SMS2 affected the formation of DAG at the Golgi apparatus. As a consequence, down-regulation of SMS1 and SMS2 reduced the localization of the DAG-binding protein, protein kinase D (PKD), to the Golgi. Since PKD recruitment to the Golgi has been implicated in cellular secretion through the trans golgi network (TGN), the effect of down-regulation of SMSs on TGN-to-plasma membrane trafficking was studied. Down regulation of either SMS1 or SMS2 significantly retarded trafficking of the reporter protein vesicular stomatitis virus G protein tagged with GFP (VSVG-GFP) from the TGN to the cell surface. Inhibition of SMSs also induced tubular protrusions from the trans Golgi network reminiscent of inhibited TGN membrane fission. Since a recent study demonstrated the requirement of PKD activity for insulin secretion in beta cells, we tested the function of SMS in this model. Inhibition of SMS significantly reduced insulin secretion in rat INS-1 cells. Taken together these results provide the first direct evidence that both enzymes (SMS1 and 2) are capable of regulating TGN-mediated protein trafficking and secretion, functions that are compatible with PKD being a down-stream target for SMSs in the Golgi

<i>Anopheles stephensi</i> as an emerging malaria vector in the Horn of Africa with high susceptibility to Ethiopian <i>Plasmodium vivax</i> and <i>Plasmodium falciparum</i> isolates

AbstractAnopheles stephensi, an efficient Asian malaria vector, recently spread into the Horn of Africa and may increase malaria receptivity in African urban areas. We assessed occurrence, genetic complexity, blood meal source and infection status of An. stephensi in Awash Sebat Kilo town, Ethiopia. We used membrane feeding assays to assess competence of local An. stephensi to P. vivax and P. falciparum isolates from clinical patients. 75.3% of the examined waterbodies were infested with An. stephensi developmental stages that were genetically closely related to isolates from Djibouti and Pakistan. Both P. vivax and P. falciparum were detected in wild-caught adult An. stephensi. Local An. stephensi was more receptive to P. vivax compared to a colony of An. arabiensis. We conclude that An. stephensi is an established vector in this part of Ethiopia, highly permissive for local P. vivax and P. falciparum isolates and presents an important new challenge for malaria control.Summary of the articleAn. stephensi, a metropolitan malaria vector that recently expanded to the Horn of African, was highly susceptible to local P. falciparum and P. vivax isolates from Ethiopia and may increase malariogenic potential of rapidly expanding urban settings in Africa.</jats:sec

Chlamydia trachomatis Co-opts GBF1 and CERT to Acquire Host Sphingomyelin for Distinct Roles during Intracellular Development

The obligate intracellular pathogen Chlamydia trachomatis replicates within a membrane-bound inclusion that acquires host sphingomyelin (SM), a process that is essential for replication as well as inclusion biogenesis. Previous studies demonstrate that SM is acquired by a Brefeldin A (BFA)-sensitive vesicular trafficking pathway, although paradoxically, this pathway is dispensable for bacterial replication. This finding suggests that other lipid transport mechanisms are involved in the acquisition of host SM. In this work, we interrogated the role of specific components of BFA-sensitive and BFA-insensitive lipid trafficking pathways to define their contribution in SM acquisition during infection. We found that C. trachomatis hijacks components of both vesicular and non-vesicular lipid trafficking pathways for SM acquisition but that the SM obtained from these separate pathways is being utilized by the pathogen in different ways. We show that C. trachomatis selectively co-opts only one of the three known BFA targets, GBF1, a regulator of Arf1-dependent vesicular trafficking within the early secretory pathway for vesicle-mediated SM acquisition. The Arf1/GBF1-dependent pathway of SM acquisition is essential for inclusion membrane growth and stability but is not required for bacterial replication. In contrast, we show that C. trachomatis co-opts CERT, a lipid transfer protein that is a key component in non-vesicular ER to trans-Golgi trafficking of ceramide (the precursor for SM), for C. trachomatis replication. We demonstrate that C. trachomatis recruits CERT, its ER binding partner, VAP-A, and SM synthases, SMS1 and SMS2, to the inclusion and propose that these proteins establish an on-site SM biosynthetic factory at or near the inclusion. We hypothesize that SM acquired by CERT-dependent transport of ceramide and subsequent conversion to SM is necessary for C. trachomatis replication whereas SM acquired by the GBF1-dependent pathway is essential for inclusion growth and stability. Our results reveal a novel mechanism by which an intracellular pathogen redirects SM biosynthesis to its replicative niche

Social media marketing strategy: definition, conceptualization, taxonomy, validation, and future agenda

Although social media use is gaining increasing importance as a component of firms’ portfolio of strategies, scant research has systematically consolidated and extended knowledge on social media marketing strategies (SMMSs). To fill this research gap, we first define SMMS, using social media and marketing strategy dimensions. This is followed by a conceptualization of the developmental process of SMMSs, which comprises four major components, namely drivers, inputs, throughputs, and outputs. Next, we propose a taxonomy that classifies SMMSs into four types according to their strategic maturity level: social commerce strategy, social content strategy, social monitoring strategy, and social CRM strategy. We subsequently validate this taxonomy of SMMSs using information derived from prior empirical studies, as well with data collected from in-depth interviews and a quantitive survey among social media marketing managers. Finally, we suggest fruitful directions for future research based on input received from scholars specializing in the field