Preparation of methanediamine (CH2(NH2)2)—A precursor to nucleobases in the interstellar medium

Although methanediamine (CH2(NH2)2) has historically been the subject of theoretical scrutiny, it has never been isolated to date. Here, we report the preparation of methanediamine (CH2(NH2)2)—the simplest diamine. Low-temperature interstellar analog ices composed of ammonia and methylamine were exposed to energetic electrons which act as proxies for secondary electrons produced in the track of galactic cosmic rays. These experimental conditions, which simulate the conditions within cold molecular clouds, . result in radical formation and initiate aminomethyl (ĊH2NH2) and amino (NH2) radical chemistry. Exploiting tunable photoionization reflectron time-of-flight mass spectrometry (PI-ReToF-MS) to make isomer-specific assignments, methanediamine was identified in the gas phase upon sublimation, while its isomer methylhydrazine (CH3NHNH2) was not observed. The molecular formula was confirmed to be CH6N2 through the use of isotopically labeled reactants. Methanediamine is the simplest molecule to contain the NCN moiety and could be a vital intermediate in the abiotic formation of heterocyclic and aromatic systems such as nucleobases, which all contain the NCN moiety

a cross-sectional study on the association between urbanicity and the acquisition of immunity

Background Malaria incidence has declined considerably over the last decade. This is partly due to a scale-up of control measures but is also attributed to increasing urbanization. This study aimed to analyse the association between malaria and urbanization and the effect of urbanicity on the acquisition of semi-immunity. Methods In 2012, children with fever presenting to St Michael’s Hospital Pramso/Ghana were recruited. The malaria-positive-fraction (MPF) of fever cases was calculated on community-level to approximate the malaria risk. The mean age of malaria cases was calculated for each community to estimate the acquisition of semi-immunity. The level of urbanicity for the communities was calculated and associations between MPF, urbanicity and immunity were modelled using linear regression. Results Twenty-six villages were included into the study with a mean MPF of 35 %. A linear decrease of 5 % (95 % CI: 4–6 %) in MPF with every ten-point increase in urbanicity was identified. The mean age of malaria patients increased by 2.9 months (95 % CI: 1.0–4.8) with every ten-point increase in urbanicity. Discussion The results confirm an association between an increase in urbanicity and declining malaria risk and demonstrate that the acquisition of semi-immunity is heterogeneous on a micro- epidemiological scale and is associated with urbanicity

Characterization of Salmonella enterica from invasive bloodstream infections and water sources in rural Ghana.

BACKGROUND: Non-typhoidal Salmonella (NTS) cause the majority of bloodstream infections in Ghana, however the mode of transmission and source of invasive NTS in Africa are poorly understood. This study compares NTS from water sources and invasive bloodstream infections in rural Ghana. METHODS: Blood from hospitalised, febrile children and samples from drinking water sources were analysed for Salmonella spp. Strains were serotyped to trace possible epidemiological links between human and water-derived isolates.. Antibiotic susceptibility testing was performed, RESULTS: In 2720 blood culture samples, 165 (6%) NTS were isolated. S. Typhimurium (70%) was the most common serovar followed by S. Enteritidis (8%) and S. Dublin (8%). Multidrug resistance (MDR) was found in 95 (58%) NTS isolates, including five S. Enteritidis. One S. Typhimurium showed reduced fluroquinolone susceptibility. In 511 water samples, 19 (4%) tested positive for S. enterica with two isolates being resistant to ampicillin and one isolate being resistant to cotrimoxazole. Serovars from water samples were not encountered in any of the clinical specimens. CONCLUSION: Water analyses demonstrated that common drinking water sources were contaminated with S. enterica posing a potential risk for transmission. However, a link between S. enterica from water sources and patients could not be established, questioning the ability of water-derived serovars to cause invasive bloodstream infections

Molecular Evidence for Flea-Borne Rickettsiosis in Febrile Patients from Madagascar.

Rickettsiae may cause febrile infections in humans in tropical and subtropical regions. From Madagascar, no molecular data on the role of rickettsioses in febrile patients are available. Blood samples from patients presenting with fever in the area of the capital Antananarivo were screened for the presence of rickettsial DNA. EDTA (ethylenediaminetetraacetic acid) blood from 1020 patients presenting with pyrexia > 38.5 °C was analyzed by gltA-specific qPCR. Positive samples were confirmed by ompB-specific qPCR. From confirmed samples, the gltA amplicons were sequenced and subjected to phylogenetic analysis. From five gltA-reactive samples, two were confirmed by ompB-specific qPCR. The gltA sequence in the sample taken from a 38-year-old female showed 100% homology with R. typhi. The other sample taken from a 1.5-year-old infant was 100% homologous to R. felis. Tick-borne rickettsiae were not identified. The overall rate of febrile patients with molecular evidence for a rickettsial infection from the Madagascan study site was 0.2% (2/1020 patients). Flea-borne rickettsiosis is a rare but neglected cause of infection in Madagascar. Accurate diagnosis may prompt adequate antimicrobial treatment

Spatial heterogeneity of malaria in Ghana: a cross-sectional study on the association between urbanicity and the acquisition of immunity.

BACKGROUND: Malaria incidence has declined considerably over the last decade. This is partly due to a scale-up of control measures but is also attributed to increasing urbanization. This study aimed to analyse the association between malaria and urbanization and the effect of urbanicity on the acquisition of semi-immunity. METHODS: In 2012, children with fever presenting to St Michael's Hospital Pramso/Ghana were recruited. The malaria-positive-fraction (MPF) of fever cases was calculated on community-level to approximate the malaria risk. The mean age of malaria cases was calculated for each community to estimate the acquisition of semi-immunity. The level of urbanicity for the communities was calculated and associations between MPF, urbanicity and immunity were modelled using linear regression. RESULTS: Twenty-six villages were included into the study with a mean MPF of 35 %. A linear decrease of 5 % (95 % CI: 4-6 %) in MPF with every ten-point increase in urbanicity was identified. The mean age of malaria patients increased by 2.9 months (95 % CI: 1.0-4.8) with every ten-point increase in urbanicity. DISCUSSION: The results confirm an association between an increase in urbanicity and declining malaria risk and demonstrate that the acquisition of semi-immunity is heterogeneous on a micro-epidemiological scale and is associated with urbanicity

Drinking water from dug wells in rural ghana--salmonella contamination, environmental factors, and genotypes.

Salmonellosis is an important but neglected disease in sub-Saharan Africa. Food or fecal-oral associated transmissions are the primary cause of infections, while the role of waterborne transmission is unclear. Samples were collected from different dug wells in a rural area of Ghana and analyzed for contamination with bacteria, and with Salmonella in particular. In addition, temporal dynamics and riks factors for contamination were investigated in 16 wells. For all Salmonella isolates antibiotic susceptibility testing was performed, serovars were determined and strains from the same well with the same serovar were genotyped. The frequency of well water contamination with Gram-negative rod-shaped bacteria was 99.2% (n = 395). Out of 398 samples, 26 (6.5%) tested positive for Salmonella spp. The serovar distribution was diverse including strains not commonly isolated from clinical samples. Resistance to locally applied antibiotics or resistance to fluoroquinolones was not seen in the Salmonella isolates. The risk of Salmonella contamination was lower in wells surrounded by a frame and higher during the rainy season. The study confirms the overall poor microbiological quality of well water in a resource-poor area of Ghana. Well contamination with Salmonella poses a potential threat of infection, thus highlighting the important role of drinking water safety in infectious disease control

Incidence and characteristics of bacteremia among children in rural Ghana.

The objective of the study was to describe systemic bacterial infections occurring in acutely ill and hospitalized children in a rural region in Ghana, regarding frequency, incidence, antimicrobial susceptibility patterns and associations with anthropometrical data.Blood cultures were performed in all children below the age of five years, who were admitted to Agogo Presbyterian Hospital (APH), Asante Region, Ghana, between September 2007 and July 2009. Medical history and anthropometrical data were assessed using a standardized questionnaire at admission. Incidences were calculated after considering the coverage population adjusted for village-dependent health-seeking behavior.Among 1,196 hospitalized children, 19.9% (n = 238) were blood culture positive. The four most frequent isolated pathogens were nontyphoidal salmonellae (NTS) (53.3%; n = 129), Staphylococcus aureus (13.2%; n = 32), Streptococcus pneumoniae (9.1%; n = 22) and Salmonella ser. Typhi (7.0%; n = 17). Yearly cumulative incidence of bacteremia was 46.6 cases/1,000 (CI 40.9-52.2). Yearly cumulative incidences per 1,000 of the four most frequent isolates were 25.2 (CI 21.1-29.4) for NTS, 6.3 (CI 4.1-8.4) for S. aureus, 4.3 (CI 2.5-6.1) for S. pneumoniae and 3.3 (CI 1.8-4.9) for Salmonella ser. Typhi. Wasting was positively associated with bacteremia and systemic NTS bloodstream infection. Children older than three months had more often NTS bacteremia than younger children. Ninety-eight percent of NTS and 100% of Salmonella ser. Typhi isolates were susceptible to ciprofloxacin, whereas both tested 100% susceptible to ceftriaxone. Seventy-seven percent of NTS and 65% of Salmonella ser. Typhi isolates were multi-drug resistant (MDR). Systemic bacterial infections in nearly 20% of hospitalized children underline the need for microbiological diagnostics, to guide targeted antimicrobial treatment and prevention of bacteremia. If microbiological diagnostics are lacking, calculated antimicrobial treatment of severely ill children in malaria-endemic areas should be considered

Comparative evaluation of the treatment efficacy of suberoylanilide hydroxamic acid (SAHA) and paclitaxel in ovarian cancer cell lines and primary ovarian cancer cells from patients

BACKGROUND: In most patients with ovarian cancer, diagnosis occurs after the tumour has disseminated beyond the ovaries. In these cases, post-surgical taxane/platinum combination chemotherapy is the "gold standard". However, most of the patients experience disease relapse and eventually die due to the emergence of chemotherapy resistance. Histone deacetylase inhibitors are novel anticancer agents that hold promise to improve patient outcome. METHODS: We compared a prototypic histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), and paclitaxel for their treatment efficacy in ovarian cancer cell lines and in primary patient-derived ovarian cancer cells. The primary cancer cells were isolated from malignant ascites collected from five patients with stage III ovarian carcinomas. Cytotoxic activities were evaluated by Alamar Blue assay and by caspase-3 activation. The ability of SAHA to kill drug-resistant 2780AD cells was also assessed. RESULTS: By employing the cell lines OVCAR-3, SK-OV-3, and A2780, we established SAHA at concentrations of 1 to 20 μM to be as efficient in inducing cell death as paclitaxel at concentrations of 3 to 300 nM. Consequently, we treated the patient-derived cancer cells with these doses of the drugs. All five isolates were sensitive to SAHA, with cell killing ranging from 21% to 63% after a 72-h exposure to 20 μM SAHA, while four of them were resistant to paclitaxel (i.e., <10% cell death at 300 nM paclitaxel for 72 hours). Likewise, treatment with SAHA led to an increase in caspase-3 activity in all five isolates, whereas treatment with paclitaxel had no effect on caspase-3 activity in three of them. 2780AD cells were responsive to SAHA but resistant to paclitaxel. CONCLUSION: These ex vivo findings raise the possibility that SAHA may prove effective in the treatment of paclitaxel-resistant ovarian cancer in vivo

Urbanicity and Paediatric Bacteraemia in Ghana-A Case-Control Study within a Rural-Urban Transition Zone.

BACKGROUND: Systemic bacterial infections are a major cause of paediatric febrile illness in sub-Saharan Africa. Aim of this study was to assess the effects of social and geographical determinants on the risk of bacteraemia in a rural-urban transition zone in Ghana. METHODS: Children below 15 years of age with fever were recruited at an outpatient department in the suburban belt of Kumasi, Ghana's second largest city. Blood was taken for bacterial culture and malaria diagnostics. The socio-economic status of participants was calculated using Principle Component Analysis. A scale, based on key urban characteristics, was established to quantify urbanicity for all communities in the hospital catchment area. A case-control analysis was conducted, where children with and without bacteraemia were cases and controls, respectively. RESULTS: Bacteraemia was detected in 72 (3.1%) of 2,306 hospital visits. Non-typhoidal Salmonella (NTS; n = 24; 33.3%) and Salmonella typhi (n = 18; 25.0%) were the most common isolates. Logistic regression analysis showed that bacteraemia was negatively associated with urbanicity (odds ratio [OR] = 0.8; 95% confidence interval [CI]: 0.7-1.0) and socio-economic status (OR = 0.8; 95% CI: 0.6-0.9). Both associations were stronger if only NTS infections were used as cases (OR = 0.5; 95% CI: 0.3-0.8 and OR = 0.6; 95% CI: 0.4-1.0, respectively). CONCLUSIONS: The results of this study highlight the importance of individual as well as community factors as independent risk factors for invasive bacterial infection (IBI) and especially NTS. Epidemiological data support physicians, public health experts and policy makers to identify disease prevention and treatment needs in order to secure public health in the transitional societies of developing countries

Antibiotic resistance and clonal diversity of invasive Staphylococcus aureus in the rural Ashanti Region, Ghana.

BACKGROUND: Staphylococcus aureus is among the most common pathogens isolated from blood cultures in Ghana; yet the epidemiology of blood infections in rural settings is poorly described. This study aims to investigate antimicrobial susceptibility and clonal diversity of S. aureus causing bloodstream infections in two hospitals in the Ashanti Region, Ghana. METHODS: Blood cultures were performed for all febrile patients (≥37.5 °C) on hospital admission. Antibiotic susceptibility testing for S. aureus isolates was carried out by the VITEK 2 system. Multiplex polymerase chain reaction (PCR) was used to detect S. aureus-specific nuc gene, Panton-Valentine leukocidin (PVL), and methicillin-resistant S. aureus (MRSA)-specific mecA and mecC genes. The population structure of S. aureus was assessed by spa typing. RESULTS: In total, 9,834 blood samples were cultured, out of which 0.6% (n = 56) were positive for S. aureus. Multidrug resistance (MDR) was detected in 35.7% (n = 20) of the S. aureus strains, of which one was a MRSA. The highest rate of antibiotic resistance was seen for commonly available antibiotics, including penicillin (n = 55; 98.2%), tetracycline (n = 32; 57.1%) and trimethoprim/sulfamethoxazole (n = 26; 46.4%). Of all S. aureus strains, 75.0% (n = 42) carried the PVL-encoding genes. We found 25 different spa types with t355 (n = 11; 19.6%), t314 (n = 8; 14.3%), t084 (n = 8; 14.3%) and t311 (n = 5; 8.9%) being predominant. CONCLUSION: The study exhibited an alarmingly large level of antibiotic resistance to locally available antibiotics. The frequency of genetically diverse and PVL-positive methicillin-sensitive S. aureus (MSSA) was high and could represent a reservoir for the emergence of virulent PVL-positive MRSA clones