Interleukin-17 and matrix metalloprotease-9 expression in the mycetoma granuloma

Mycetoma is a persistent, progressive granulomatous inflammatory disease caused either by fungi or by bacteria. Characteristic of this disease is that the causative agents organise themselves in macroscopic structures called grains. These grains are surrounded by a massive inflammatory reaction. The processes leading to this host tissue reaction and the immunophenotypic characteristics of the mycetoma granuloma are not known. Due to the massive immune reaction and the tissue remodeling involved, we hypothesised that the expression levels of interleukin-17 (IL-17) and matrix metalloprotease-9 (MMP-9) in the mycetoma granuloma formation were correlated to the severity of the disease and that this correlation was independent of the causative agent responsible for the granuloma reaction. To determine the expression of IL-17 and MMP-9 in mycetoma lesions, the present study was conducted at the Mycetoma Research Centre, Sudan. Surgical biopsies from 100 patients with confirmed mycetoma were obtained, and IL-17 and MMP-9 expression in the mycetoma granuloma were evaluated immunohistochemically. IL-17 was mainly expressed in Zones I and II, and far less in Zone III. MMP-9 was detected mainly in Zones II and III, and the least expression was in Zone I. MMP-9 was more highly expressed in Actinomadura pelletierii and Streptomyces somaliensis biopsies compared to Madurella mycetomatis biopsies. MMP-9 levels were directly proportional to the levels of IL-17 (p = 0.001). The only significant association between MMP9 and the patients' characteristics was the disease duration (

Reproducibility of the ribosomal RNA synthesis ratio in sputum and association with markers of mycobacterium tuberculosis burden

The MIND-IHOP study was funded by the IHOP grant (NIH R01 HL090335), Lung MicroCHIP grant (NIH U01 HL098964), and K24 grant (NIH K24 HL087713). These sources provided the funding to support participant enrollment and specimen collection. Emmanuel Musisi was supported by a scholarship from the Pulmonary Complications of AIDS Research Training Program (NIH D43 TW009607). N.D.W., R.M.S., J.L.D., and P.N. acknowledge funding from the U.S. National Institutes of Health (1R01AI127300-01A1). N.D.W. and M.I.V. acknowledge funding from the U.S. National Institutes of Health (1R21AI135652-01). N.D.W. acknowledges funding from Veterans Affairs (1IK2CX000914-01A1 and 1I01BX004527-01A1) and from the Doris Duke Charitable Foundation Clinical Scientist Development Award.There is a critical need for improved pharmacodynamic markers for use in human tuberculosis (TB) drug trials. Pharmacodynamic monitoring in TB has conventionally used culture or molecular methods to enumerate the burden of Mycobacterium tuberculosis organisms in sputum. A recently proposed assay called the rRNA synthesis (RS) ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis. Here, we evaluated RS ratio as a potential pharmacodynamic monitoring tool by testing pretreatment sputa from 38 Ugandan adults with drug-susceptible pulmonary TB. We quantified the RS ratio in paired pretreatment sputa and evaluated the relationship between the RS ratio and microbiologic and molecular markers of M. tuberculosis burden. We found that the RS ratio was highly repeatable and reproducible in sputum samples. The RS ratio was independent of M. tuberculosis burden, confirming that it measures a distinct new property. In contrast, markers of M. tuberculosis burden were strongly associated with each other. These results indicate that the RS ratio is repeatable and reproducible and provides a distinct type of information from markers of M. tuberculosis burden. Importance This study takes a major next step toward practical application of a novel pharmacodynamic marker that we believe will have transformative implications for tuberculosis. This article follows our recent report in Nature Communications that an assay called the rRNA synthesis (RS) ratio indicates the treatment-shortening of drugs and regimens. Distinct from traditional measures of bacterial burden, the RS ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis.Publisher PDFPeer reviewe

Short and long-term forecasting by the Netherlands Bureau for Economic Policy Analysis (CPB): science, witchcraft, or practical tool for policy?

This paper discusses five different types of forecasts by CPB: forecasts for next year, forecasts for next period of government, analyses of the sustainability of public finance, long-term scenarios and long-term effects of election platforms. CPB forecasts for next year and for the next period of government should be seen as well-motivated estimates based on all recent information, plausible assumptions and expected trends. The more distant the look into the future, the more uncertain are the forecasts. For such long-term analyses, the CPB employs scenarios, extended sensitivity analyses and identification of major political choices. Policy making is like sailing in fog. The regular set of CPB forecasts helps to look forward and to monitor whether a change of course is necessary. Despite fundamental uncertainty about the future, the CPB forecasts provide a good base for political discussions and decision making, like a coalition agreement, budget and wage rate negotiations and defining a long-term policy strategy. These forecasts inform Dutch society, reduce transaction costs in economic and political decision making, and foster consensus on economic and fiscal policy

A geographical analysis of ethnic distribution of jaw ameloblastoma in Nigerians

Introduction: Ameloblastoma is the most common odontogenic tumour in Nigeria. A definite geographic variation has been observed in the frequency of odontogenic tumors from different parts of the world. However, there is no study on the regional variations in Nigeria. Hence, this study was designed to document the ethnic and geographical distribution of jaw ameloblastoma in Nigeria.Methods: Archival data on ameloblastoma from 10 health facilities were obtained. Global Moran’s I detected geographic clustering in its distribution while Local Getis Ord indicated the location of ameloblastoma clusters. Chi-square tested associations between variables at 0.05 level of significance.Results: A total of 1,246 ameloblastoma cases were recorded in Nigeria. Besides substantial state variations, a South-North gradient was noticed in its distribution. Significant positive spatial autocorrelation was observed in the three major groups while ameloblas- toma hotspots were found in the SouthWestern and Northwestern Nigeria. The Igbos had a higher prevalence of ameloblastoma outside their home region than within.Conclusion: The study hypothesized that the geographical distribution of ameloblastoma in Nigeria is the result of all or one of the following:  the country’s tropical climate, migration patterns and health seeking behavior. Hopefully, these claims should lead to further enquiry on the underlying causes.Keywords: Ameloblastoma, ethnicity, spatial analysis, Nigeria

Epidemiology and antimicrobial resistance trends of Acinetobacter species in the United Arab Emirates: a retrospective analysis of 12 years of national AMR surveillance data

Introduction: Acinetobacter spp., in particular A. baumannii, are opportunistic pathogens linked to nosocomial pneumonia (particularly ventilator-associated pneumonia), central-line catheter-associated blood stream infections, meningitis, urinary tract infections, surgical-site infections, and other types of wound infections. A. baumannii is able to acquire or upregulate various resistance determinants, making it frequently multidrug-resistant, and contributing to increased mortality and morbidity. Data on the epidemiology, levels, and trends of antimicrobial resistance of Acinetobacter spp. in clinical settings is scarce in the Gulf Cooperation Council (GCC) and Middle East and North Africa (MENA) regions. Methods: A retrospective 12-year analysis of 17,564 non-duplicate diagnostic Acinetobacter spp. isolates from the United Arab Emirates (UAE) was conducted. Data was generated at 317 surveillance sites by routine patient care during 2010-2021, collected by trained personnel and reported by participating surveillance sites to the UAE National AMR Surveillance program. Data analysis was conducted with WHONET. Results: Species belonging to the A. calcoaceticus-baumannii complex were mostly reported (86.7%). They were most commonly isolated from urine (32.9%), sputum (29.0%), and soft tissue (25.1%). Resistance trends to antibiotics from different classes during the surveillance period showed a decreasing trend. Specifically, there was a significant decrease in resistance to imipenem, meropenem, and amikacin. Resistance was lowest among Acinetobacter species to both colistin and tigecycline. The percentages of multidrug-resistant (MDR) and possibly extensively drug-resistant (XDR) isolates was reduced by almost half between the beginning of the study in 2010 and its culmination in 2021. Carbapenem-resistant Acinetobacter spp. (CRAB) was associated with a higher mortality (RR: 5.7), a higher admission to ICU (RR 3.3), and an increased length of stay (LOS; 13 excess inpatient days per CRAB case), as compared to Carbapenem-susceptible Acinetobacter spp. Conclusion: Carbapenem-resistant Acinetobacter spp. are associated with poorer clinical outcomes, and higher associated costs, as compared to carbapenem-susceptible Acinetobacter spp. A decreasing trend of MDR Acinetobacter spp., as well as resistance to all antibiotic classes under surveillance was observed during 2010 to 2021. Further studies are needed to explore the reasons and underlying factors leading to this remarkable decrease of resistance over time

A geographical analysis of ethnic distribution of jaw ameloblastoma in Nigerians

Introduction: Ameloblastoma is the most common odontogenic tumour in Nigeria. A definite geographic variation has been observed in the frequency of odontogenic tumors from different parts of the world. However, there is no study on the regional variations in Nigeria. Hence, this study was designed to document the ethnic and geographical distribution of jaw ameloblastoma in Nigeria. Methods: Archival data on ameloblastoma from 10 health facilities were obtained. Global Moran\u2019s I detected geographic clustering in its distribution while Local Getis Ord indicated the location of ameloblastoma clusters. Chi-square tested associations between variables at 0.05 level of significance. Results: A total of 1,246 ameloblastoma cases were recorded in Nigeria. Besides substantial state variations, a South-North gradient was noticed in its distribution. Significant positive spatial autocorrelation was observed in the three major groups while ameloblastoma hotspots were found in the SouthWestern and Northwestern Nigeria. The Igbos had a higher prevalence of ameloblastoma outside their home region than within. Conclusion: The study hypothesized that the geographical distribution of ameloblastoma in Nigeria is the result of all or one of the following: the country\u2019s tropical climate, migration patterns and health seeking behavior. Hopefully, these claims should lead to further enquiry on the underlying causes. DOI: https://dx.doi.org/10.4314/ahs.v19i1.44 Cite as: Adisa AO, Osayomi T, Effiom OA, Kolude B, Lawal AO, Soyele OO, et al. A geographical analysis of ethnic distribution of jaw ameloblastoma in Nigerians. Afri Health Sci. 2019;19(1). 1677-1686. https://dx.doi.org/10.4314/ ahs. v19i1.4

Varicellovirus UL49.5 Proteins Differentially Affect the Function of the Transporter Associated with Antigen Processing, TAP

Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in MHC class I–restricted antigen presentation, as TAP imports peptides into the ER, where peptide loading of MHC class I molecules takes place. In this study, the UL49.5 proteins of the varicelloviruses bovine herpesvirus 1 (BHV-1), pseudorabies virus (PRV), and equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are characterized as members of a novel class of viral immune evasion proteins. These UL49.5 proteins interfere with MHC class I antigen presentation by blocking the supply of antigenic peptides through inhibition of TAP. BHV-1, PRV, and EHV-1 recombinant viruses lacking UL49.5 no longer interfere with peptide transport. Combined with the observation that the individually expressed UL49.5 proteins block TAP as well, these data indicate that UL49.5 is the viral factor that is both necessary and sufficient to abolish TAP function during productive infection by these viruses. The mechanisms through which the UL49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 block TAP exhibit surprising diversity. BHV-1 UL49.5 targets TAP for proteasomal degradation, whereas EHV-1 and EHV-4 UL49.5 interfere with the binding of ATP to TAP. In contrast, TAP stability and ATP recruitment are not affected by PRV UL49.5, although it has the capacity to arrest the peptide transporter in a translocation-incompetent state, a property shared with the BHV-1 and EHV-1 UL49.5. Taken together, these results classify the UL49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms

Perinatal mortality and its predictors in Beni City, Democratic Republic of Congo: a cross-sectional study

Abstract Background Globally, perinatal mortality rates have decreased considerably in the last 30 years. However, in sub-Saharan African countries perinatal mortality remains a public health burden. Therefore, this study aimed to determine the Perinatal Mortality Rate and the factors associated with perinatal mortality in Beni City, Northeastern Democratic Republic of Congo. Methods A hospital-based retrospective cross-sectional study was conducted among 1394 deliveries that were documented in Beni General Referral Hospital from 2 January to May 31, 2022. The study was done in the conflict-ridden Beni city of the North Kivu Province. Analysis was done using Open Epi and SPSS version 22. Binary and Multivariate logistic regression analyses were performed. Odds ratio with 95% confidence interval was used to measure strength of association. Results Findings indicate that 60.7% of 1394 participants were below the age of 21 years, and 95.1% (1325) Beni residents. The Perinatal Mortality Rate was 42.3 per 1000 live births. Majority (51) of the postpartum women who experienced perinatal mortality didn`t have a history of perinatal mortality as compared to their counterparts. Multivariable analysis revealed that birth weight (AoR = 0.082, 95% CI 0.014–0.449, p < 0.05) and Apgar score in the 10th minute (AoR = 0.082, 95% CI 0.000- 0.043, p < 0.05) were significantly associated with Perinatal mortality. Conclusion The high perinatal mortality rate in Beni General Referral Hospital, approximately four in every 100 births remains a disturbing public health concern of which is attributable to low birth weight and Apgar score. This study may help policy-makers and healthcare providers to design preventive interventions

Conservative management of post-traumatic cerebral myiasis: report of a unique case and literature review

Cerebral myiasis is extremely rare, and surgical intervention is the primary treatment used. Successful conservative management alone, without surgical removal of the brain infestation has not yet been published. We report the a case of a 24-year-old African homeless man who was found on the street in a state of decreased level of consciousness, with larvae exiting from the left supra and postauricular dirty wounds and from his left ear. The patient was diagnosed with post-traumatic cerebral myiasis of the left temporal lobe and cerebellum. It was treated successfully by debridement of the external wounds and administration of antibiotics, without surgical removal of the brain infestations. For the first time, this case illustrates the novelty and appropriateness of the conservative management of cerebral myiasis. This is also the first report of cerebral myiasis with cerebellar involvement and the second report of post-traumatic cerebral myiasis in literature. Continuous..