Determination of process-related impurities in <Emphasis Type="Italic">N</Emphasis>-acetylglucosamine prepared by chemical and enzymatic methods: structural elucidation and quantification

β-N-acetylglucosamine (β-AG) is a monosaccharide distributed widely in living organisms with various pivotal roles. The presence of particulates and impurities can affect the safety and efficacy of a product for its intended duration of use. Thus, the current study was carried out to identify and quantify the potentially-harmful process related impurities; namely α-N,6-diacetylglucosamine (α-DAG) and α-N-acetylglucosamine (α-AG), derived from the chemical and enzymatic synthesis of β-AG. The impurities were characterized using a high resolution mass spectrometry, a nuclear magnetic resonance spectroscopy, and liquid chromatography-tandem mass spectrometry (LC/MS/MS). The developed method showed a good linearity (R ² ≥ 0.998), satisfactory precision (≤6.1 % relative standard deviation), intra- and inter-day accuracy (88.20–97.50 %), extraction recovery (89.30–110.50 %), matrix effect (89.70–105.20 %), and stability (92.70–101.60 %). The method was successfully applied to determine the level of α-DAG that was 3.04 and 0.07 % of the total β-AG, following chemical and enzymatic methods, respectively. It can be concluded that the enzymatic rather than the chemical method is more efficient for the synthesis of β-AG. Characterization of impurities heeds the signal for acquiring and evaluating data that establishes biological safety.     

Serum interleukin-30 level in patients with psoriasis and its correlation with psoriasis severity: a case-control study

ObjectivesTo examine the serum levels of interleukin (IL)-30 in patients with psoriasis and evaluate the correlations with the Psoriasis Area and Severity Index (PASI).MethodsSerum was collected from 26 patients with psoriasis and 26 healthy controls in a case–control setting, and the level of IL-30 was determined using an enzyme-linked immunosorbent assay. Statistical analysis of the IL-30 levels among groups and further correlation analyses of IL-30 levels with PASI scores were performed.ResultsA significant increase in the level of IL-30 in patients with psoriasis compared with healthy controls was observed. In addition, a positive correlation between the IL-30 concentration and PASI scores was found in patients with psoriasis.ConclusionIL-30 is presumably involved in the proliferation of epidermal cells during the development of psoriasis. Further studies with a larger number of participants are required to comprehensively elucidate the biological roles of IL-30 in the pathogenesis of psoriasis.     

Socio-economic,trafficking exposures and mental health symptoms of human trafficking returnees in Ethiopia: using a generalized structural equation modelling

Background

Mental health problems among trafficked persons could be the result of concomitantly interwoven effects of various factors. Analyzing the networked relationships concurrently could be a more substantive approach to better understand the role of risk factors in this population. This study aimed to assess the magnitude of mental health symptoms as well as the association among socio-demographic, trafficking related exposure variables, and mental health problems of Ethiopian returnees from trafficking.

Methods

A sample of 1387 returnees who were trafficked via three major human trafficking corridors of Ethiopia were selected consecutively. Data related to socio-economic, trafficking exposure variables, and symptoms of mental illness were collected in personal interviews. Anxiety was measured with a brief measure for generalized anxiety disorder (GAD-7), depression with a patient health questionnaire (PHQ-9), and PTSD with post-traumatic checklist (PCL-C). Generalized structural equation modeling was employed to estimate the relationships among exogenous, mediating, and endogenous variables simultaneously.

Results

The prevalence of symptoms of anxiety was estimated at 51.9% (95% CI 49.3–54.6%); PTSD was estimated at 34.5% (95% CI 32.1–37.1%) and depression at 58.3% (95% CI 55.6–60.9%). Restricted freedom of movement had a direct positive effect on anxiety (β?=?1.24, 95% CI 0.97–1.51), depression (β?=?0.94, 95% CI 0.71–1.17) and PTSD (13.00, 95% CI 11.23–14.77). Violence experienced during the trafficking period was a mediator variable and significantly associated with anxiety (β?=?0.46; 95% CI 0.26–0.66) and PTSD (β?=?4.00; 95% CI 2.06–5.94). History of detention had a positive total effect on GAD (total β?=?1.380, 95% CI 1.074–1.687) and PTSD (total β?=?15.63, 95% CI 13.708–17.545), and direct positive effect on depression (β?=?0.89, 95% CI 0.65–1.13).

Conclusion

Ethiopian trafficked persons were highly likely to return with increased levels of mental health symptoms, namely anxiety, depression, and PTSD. Socio-economic and trafficking related exposures mediated by violence were factors affecting mental health symptoms. Thus, in addition to economic re-integrations of victims, strategies should be designed and implemented to address the prevalent mental health problems.

     

Outcome of elderly patients after failure to hypomethylating agents given as frontline therapy for acute myeloid leukemia: Single institution experience*

Outcomes of acute myeloid leukemia (AML) in elderly patients unfit for intensive chemotherapy is challenging. Hypomethylating agents (HMAs) can be effective in these patients but responses are usually short‐lived. The majority of patients will either have stable disease or progress through therapy. We hereby describe the outcome of these patients at our institution after they fail HMAs. The data on 56 AML patients at Mayo Clinic, Rochester were reviewed. Patients were considered for our study if they received HMA as frontline therapy for their AML. Out of 56 patients, 15 (27%) patients received azacitidine (AZA) and 41 (73%) received decitabine. Complete remission was found in 10 (18%), with overall response of 28% and median response duration of 10 months. Thirteen (81%) out of 16 responders relapsed. Therefore 53 patients were included in the primary or secondary failure analysis with a median overall survival (OS) of 2 months after the date of failure. Out of 53 patients, 12 (23%) received subsequent treatments. None of the 12 patients who got first salvage therapy achieved remission. Five out of the 12 patients received second salvage therapy, 2 (40%) of which achieved CR. Median OS for patients who received subsequent salvage therapies was better than those who did not receive any subsequent therapy after failing HMA (9.5 vs. 2 months, P = .0009). Outcome for patients who have primary or secondary failure is very poor. Our study provides important historical data for future novel therapies, which are sorely needed for these patients.     

Ruptured splenic artery aneurysm as a rare cause of acute abdomen; a case report done at Tikur Anbessa Specialized Hospital, Addis Ababa

Splenic artery aneurysm is a rare phenomenon although it is the second most common visceral artery aneurysm. Usually it occurs in adults with an increase in incidence as age increases and the diagnosis is made incidentally during work-up of patients for other clinical conditions. When it ruptures life threatening hemorrhage occurs and patients usually die if the correct diagnosis is not made timely. Here we present a ruptured splenic artery aneurysm which was misdiagnosed as a hemorrhagic pancreatitis and finally the diagnosis was made on post contrast computed tomography scan. Physicians must include ruptured splenic artery aneurysm as one of the differential diagnosis of acute abdomen particularly in patients who are in shock state and anemic.     

Trimethoprim as Adjuvant Treatment in Schizophrenia: A Double-Blind,Randomized, Placebo-Controlled Clinical Trial

Various infectious agents, such as Toxoplasma gondii, have been hypothesized to be potentially relevant etiological factors in the onset of some cases of schizophrenia. We conducted a randomized, double-blind, placebo-controlled treatment trial in an attempt to explore the hypothesis that the symptoms of schizophrenia may be related to infection of the central nervous system with toxoplasma gondii. Systematically selected patients with ongoing and at least moderately severe schizophrenia from Butajira, in rural Ethiopia, were randomly allocated to trimethoprim or placebo, which were added on to participants'' regular antipsychotic treatments. Trial treatments were given for 6 months. The Positive and Negative Syndrome Scale (PANSS) was used to assess outcome. Ninety-one patients were included in the study, with 80 cases (87.9%) positive for T. gondii immunoglobulin G antibody. Seventy-nine subjects (87.0%) completed the trial. The mean age of subjects was 35.3 (SD = 8.0) years, with a mean duration of illness of 13.2 (SD = 6.7) years. Both treatment groups showed significant reduction in the overall PANSS score with no significant between-group difference. In this sample of patients with chronic schizophrenia, trimethoprim used as adjuvant treatment is not superior to placebo. However, it is not possible to draw firm conclusion regarding the etiological role of toxoplasmosis on schizophrenia based on this study because the timing and the postulated mechanisms through which toxoplasmosis produces schizophrenia are variable.     

High levels of misconceptions and stigma in a community highly endemic for podoconiosis in southern Ethiopia

The impact of public health interventions for tropical diseases is limited by lack of understanding of the sociocultural context into which these interventions are delivered. Podoconiosis (endemic non-filarial elephantiasis) is a considerable public health problem in Ethiopia, yet little is known about community understanding of it. This study aimed to assess the knowledge, attitudes and practices of community members towards podoconiosis in a highly endemic area in southern Ethiopia. A cross-sectional study was conducted in January 2007 among 438 study participants selected by multistage probability sampling. Most respondents (93.5%) had seen a patient with podoconiosis and 91.6% had heard of the local terms for podoconiosis. The proportion of respondents holding at least one misconception about causation was 93.4% (95% CI 91.1-95.7%). More than one-half (55.8%) showed stigmatising attitudes towards social interactions with podoconiosis patients and 63.8% had unfavourable attitudes towards the condition. Just over one-half (55.2%) of respondents were wearing shoes during the interview, but shoe wearing was inconsistent and inadequate to prevent podoconiosis. In this highly endemic area, the community held significant misconceptions about causation, care, treatment and prevention of podoconiosis. Community interventions for podoconiosis must include education components aimed at dispelling misconceptions and stigma.     

Impact assessment of gilgel gibe hydroelectric dam on schitosomiasis: a cross sectional study in southwest ethiopia

Background

Intestinal schistosomiasis is prevalent in East Africa including Ethiopia. Constructed five years back, Gilgel Gibe dam is suspected to harbor the intermediate host for transmission of schistosomiasis. The objective of this study was to determine the prevalence of intestinal schistosomiasis and risk factors among school children.

Methods

A comparative cross-sectional study was carried out in October 2008 in four Woredas bordering Gilgel Gibe dam, within 10 kilometers, and Bulbul, which is 30 Kms away from the dam. Children attending grades 1–8 in the schools located adjacent to the dam constituted the cases and those living in Bulbul constitute the controls. Using Epinfo version 6.0 for cross-sectional study, a sample size of 937 was determined. Sample size allocation was done 2:1 for cases and control. After interview, stool sample was collected and analyzed. Screening for the presence of intermediate host and physiochemical analyses of selected water bodies along the major water contact sites of the reservoir was also done Data were entered into computer and analyzed using SPSS for windows version 13.0.1.

Results

Out of 624 sampled cases and 312 controls, 585 and 270 participated in the study giving a response rate of 93.8% and 86.5%, respectively. Four hundred seventy four (81.0% of the cases and 203 (75.2%) controls use latrine regularly. On stool examination, 406 (47.5%) children, 295 (50.4%) cases and 111 (41.1%) controls) were positive to intestinal parasites but only two children, both from the control groups, were positive for Schistosoma mansoni. The three river water samples on which malacological survey was done had similar physicochemical characteristics in many ways except high conductivity, pH and percent of dissolved oxygen concentration (milligram per liter) at one site where uninfected Biomphilaria Pfeifferi was found

Conclusion

The study revealed that schistosomiasis is not yet a problem at Gilgel-Gibe dam. But, continuous surveying is required as the intermediate host is prevalent, the water bodies are suitable for the intermediate host and cases of schistosomiasis are identified 30 kms away the dam, in control area.     

The Myelofibrosis Symptom Assessment Form (MFSAF): An evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis

Quality of life (QoL) in patients with myelofibrosis (MF) is severely compromised by severe constitutional symptoms (i.e. fatigue, night sweats, fever, weight loss), pruritus, and symptoms from frequently massive hepatosplenomegaly. Given that no current instrument of patient reported outcomes (PRO) exists that covers the unique spectrum of symptomatology seen in MF patients, we sought to develop a new PRO instrument for MF patients for use in therapeutic clinical trials. Utilizing data from an international Internet-based survey of 458 patients with MF we created a 20-item instrument (MFSAF: Myelofibrosis Symptom Assessment Form) which measures the symptoms reported by >10% of MF patients and includes a measure of QoL. We subsequently validated the MFSAF in a prospective trial of MF patients involving patient and provider feedback, as well as comparison to other validated instruments used in cancer patients. The MFSAF results were highly correlated with other instruments, judged comprehensive and understandable by patients, and should be considered for evaluation of MF symptoms in therapeutic trials.     

Multidrug-resistant tuberculosis in central Asia

Multidrug-resistant tuberculosis (MDR-TB) has emerged as a major threat to TB control, particularly in the former Soviet Union. To determine levels of drug resistance within a directly observed treatment strategy (DOTS) program supported by Médecins Sans Frontières in two regions in Uzbekistan and Turkmenistan, Central Asia, we conducted a cross-sectional survey of smear-positive TB patients in selected districts of Karakalpakstan (Uzbekistan) and Dashoguz (Turkmenistan). High levels of MDR-TB were found in both regions. In Karakalpakstan, 14 (13%) of 106 new patients were infected with MDR-TB; 43 (40%) of 107 previously treated patients were similarly infected. The proportions for Dashoguz were 4% (4/105 patients) and 18% (18/98 patients), respectively. Overall, 27% of patients with positive smear results whose infections were treated through the DOTS program in Karakalpakstan and 11% of similar patients in Dashoguz were infected with multidrug-resistant strains of TB on admission. These results show the need for concerted action by the international community to contain transmission and reduce the effects of MDR-TB.