Indicators of Asthma Control in Asthmatic Patients: Are they related to Depression?

BACKGROUND: Many patients with chronic illnesses suffer from depression. A poorly controlled asthma that presents with repeated attacks of breathlessness is a recognised risk factor for bipolar disorders. On the other hand, depression can aggravate asthma symptoms.AIM: The aim of this study is to determine the indicators of the asthma control test (ACT) among the asthmatic patients who attend the outpatient clinic for follow-up and to investigate the relation between these indicators and clinical depression, using a standardised depression scale.METHODS: A total of 38 adult asthmatic patients (29 women, age 17–85 years), with variable levels of control, were assessed using the ACT and the Beck Depression Inventory (BDI). Data obtained were analysed with the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL, USA) version 20. The association of depression with the various indicators of asthma control was analysed with the Chi-Square test. Statistical significance was determined at p< 0.05.RESULTS: The uncontrolled asthma is associated with depression in 37% of all participants compared to 0% in the well-controlled group (p = 0.002). Depression is significantly related to asthma interference with daily activities (p = 0.003), breathlessness (p < 0.001), night symptoms (p = 0.036), use of bronchodilators (p = 0.007), and poor compliance with medical treatment (p = 0.003). The poor educational attainment and comorbidities have significant relations to both uncontrolled asthma and clinical depression (p < 0.05).CONCLUSION: All indicators of the poor asthma control are associated with clinical depression. A significant proportion of the uncontrolled asthma patients suffers from depression. The possibility of improving asthma control with a pharmacological treatment of depression has to be considered

Artesunate plus sulfadoxine-pyrimethamine for treatment of uncomplicated Plasmodium falciparum malaria in Sudan

BACKGROUND: Early diagnosis and effective treatment with an appropriate drug form the main components of the World Health Organization's strategy to reduce malaria related mortality. The few available drugs might be safeguarded if combined with artesunate. The addition of artesunate to a standard antimalarial treatment substantially reduces treatment failure, recrudescence and gametocyte carriage. METHODS: During late 2004, the efficacy of artesunate (4 mg/kg. day, on days 0–2) plus sulfadoxine-pyrimethamine (25 mg/kg, on day 0) for the treatment of uncomplicated Plasmodium falciparum malaria was investigated in four sentinel areas in Sudan, with different malaria transmission (Damazin, Kassala, Kosti, and Malakal). RESULTS: Two hundreds and sixty-nine patients completed the 28-day follow-up. On day one, 60 (22.3%) patients were febrile and 15 (5.5%) patients were parasitaemic. On day three, all the patients were afebrile and aparasitaemic. While two patients (0.7%, Kassala) showed late Clinical and Parasitological Failures, the rest (99.3%) of the patients demonstrated Adequate Clinical and Parasitological Response. A gametocytaemia were detected during the follow-up in one patient (0.37%, Kassala). Adverse drug effects were detected in 32 (11.9%) patients CONCLUSION: The study showed that AS plus SP is an effective, safe drug in the treatment of uncomplicated P. falciparum malaria in Sudan

ZAP-70 Expression in B-Chronic Lymphocytic Leukemia in Sudanese Patients

Background: Chronic lymphocytic leukemia is the most common form of leukemia in adults. The prognostic impact of ZAP-70 in CLL has been reported in several studies. The aim of conducting this study was to investigate the prevalence of ZAP-70 in Sudanese patients with chronic lymphocytic leukemia attending Khartoum Oncology Hospital.Materials and Methods: A total of 93 newly diagnosed patients with chronic lymphocytic leukemia were enrolled in this study. Lymphadenopathy and organomegaly were assessed in all participants using clinical examination, chest radiography, and abdominal ultrasound. Full blood count was carried out by an automated hematology analyzer. ZAP-70 was evaluated using flowcytometry on peripheral blood samples. ZAP-70 was defined as positive expression at a cutoff level of 20%. Results: There were 63 (67.7%) males and 30 (32.3%) females and the median age of the group was 63 years; 68 patients (73.1%) were presented with anemia and 66(70.9%) had lymphadenopath;y. Majority of our patients 35 (37.6%) were in Rai stage IV. ZAP-70 positivity was detected in 21 patients (22.6%). There was no statistically significant association of ZAP-70 with age, sex, lymphadenopathy, organomegaly, hemoglobin concentration, total white blood cell count, platelet count and Rai staging system (p-value > 0.05). Conclusion: Only 21 patients (22.6%) were ZAP-70 positive. There was no association between ZAP-70 and the study variables. Further studies to evaluate prognostic role of ZAP-70 in Sudanese patients with chronic lymphocytic leukemia are recommended

Histopathological Features of Methotrexate Induced Pulmonary Lesions in Rheumatoid Arthritis Patients: A Systematic Review of Case Reports

BACKGROUND: Methotrexate (MTX) is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA); however, it causes many side effects, including pulmonary lesions. In this review, we characterised the histopathological features of MTX-induced pulmonary lesions in RA patients.AIM: We carried out an electronic search of the relevant literature published during the period from 1990 to 2016. We included only the cases with definitive histo-pathological findings caused by MTX therapy.MATERIAL AND METHODS: The total number of cases is 27. Male: female ratio was 1:3, and ages ranged from 48 to 87 years old, with a mean (SD) = 65.7 (1.0). The cases were originally from Asia (55%), Europe (41%), and America (4%). The major complications of methotrexate therapy were lymphoproliferative disorders (42%) followed by interstitial fibrosis (33), and infections (25%). The incidence of these complications significantly increases with the duration of MTX treatment (p = 0.044). Among the infections, the most common causative organism was pneumocystis jiroveci. The majority of patients who developed infections following methotrexate therapy were from Europe whereas the majority of those who developed lymphoproliferative disorders were from Asia (p = 0.003).CONCLUSION: In conclusion, methotrexate therapy in rheumatoid arthritis patients causes different types pulmonary complications

Clear Cell Renal Cell Carcinoma is linked to Epithelial‐to‐Mesenchymal Transition and to Fibrosis

Clear cell renal cell carcinoma (ccRCC) represents the most common type of kidney cancer with high mortality in its advanced stages. Our study aim was to explore the correlation between tumor epithelial‐to‐mesenchymal transition (EMT) and patient survival. Renal biopsies of tumorous and adjacent nontumorous tissue were taken with a 16 g needle from our patients (n = 26) undergoing partial or radical nephrectomy due to ccRCC. RNA sequencing libraries were generated using Illumina TruSeq® Access library preparation protocol and TruSeq Small RNA library preparation kit. Next generation sequencing (NGS) was performed on Illumina HiSeq2500. Comparative analysis of matched sample pairs was done using the Bioconductor Limma/voom R‐package. Liquid chromatography‐tandem mass spectrometry and immunohistochemistry were applied to measure and visualize protein abundance. We detected an increased generic EMT transcript score in ccRCC. Gene expression analysis showed augmented abundance of AXL and MMP14, as well as down‐regulated expression of KL (klotho). Moreover, microRNA analyses demonstrated a positive expression correlation of miR‐34a and its targets MMP14 and AXL. Survival analysis based on a subset of genes from our list EMT‐related genes in a publicly available dataset showed that the EMT genes correlated with ccRCC patient survival. Several of these genes also play a known role in fibrosis. Accordingly, recently published classifiers of solid organ fibrosis correctly identified EMT‐affected tumor samples and were correlated with patient survival. EMT in ccRCC linked to fibrosis is associated with worse survival and may represent a target for novel therapeutic interventions.Peer reviewe

Effect of different concentrations of soybean lecithin and virgin coconut oil in Tris-based extender on the quality of chilled and frozen-thawed bull semen

Aim: The objective of this study was to evaluate the effects of different concentrations of soybean lecithin (SL) and virgin coconut oil (VCO) in Tris-based extender on chilled and frozen-thawed bull semen quality parameters. Materials and Methods: A total of 24 ejaculates were collected from four bulls via an electroejaculator. Semen samples were diluted with 2% VCO in Tris-based extender which consists of various concentrations of SL (1, 1.25, 1.5, and 1.75%). A 20% egg yolk in Tris used as a positive control (C+). The diluted semen samples were divided into two fractions; one for chilling which were stored at 4°C for 24, 72, and 144 h before evaluated for semen quality parameters. The second fraction used for freezing was chilled for 3 h at 4°C, packed into 0.25 mL straws and then cryopreserved in liquid nitrogen. The samples were then evaluated after 7 and 14 days. Chilled and frozen semen samples were thawed at 37°C and assessed for general motility using computer-assisted semen analysis, viability, acrosome integrity and morphology (eosin-nigrosin stain), membrane integrity, and lipid peroxidation using thiobarbituric acid reaction test. Results: The results showed that all the quality parameters assessed were significantly (p<0.05) improved at 1.5% SL concentration in chilled semen. Treatment groups of 1, 1.25, 1.5, and 1.75% SL were higher in quality parameters than the control group (C+) in chilled semen. However, all the quality parameters in frozen-thawed semen were significantly higher in the C+ than the treated groups. Conclusion: In conclusion, supplementation of 1.5% SL in 2% VCO Tris-based extender enhanced the chilled bull semen. However, there was no marked improvement in the frozen-thawed quality parameters after treatment

Feasibility and acceptability of home-based management of malaria strategy adapted to Sudan's conditions using artemisinin-based combination therapy and rapid diagnostic test

<p>Abstract</p> <p>Background</p> <p>Malaria remains a major public health problem especially in sub-Saharan Africa. Despite the efforts exerted to provide effective anti-malarial drugs, still some communities suffer from getting access to these services due to many barriers. This research aimed to assess the feasibility and acceptability of home-based management of malaria (HMM) strategy using artemisinin-based combination therapy (ACT) for treatment and rapid diagnostic test (RDT) for diagnosis.</p> <p>Methods</p> <p>This is a study conducted in 20 villages in Um Adara area, South Kordofan state, Sudan. Two-thirds (66%) of the study community were seeking treatment from heath facilities, which were more than 5 km far from their villages with marked inaccessibility during rainy season. Volunteers (one per village) were trained on using RDTs for diagnosis and artesunate plus sulphadoxine-pyrimethamine for treating malaria patients, as well as referral of severe and non-malaria cases. A system for supply and monitoring was established based on the rural health centre, which acted as a link between the volunteers and the health system. Advocacy for the policy was done through different tools. Volunteers worked on non-monetary incentives but only a consultation fee of One Sudanese Pound (equivalent to US$0.5).</p> <p>Pre- and post-intervention assessment was done using household survey, focus group discussion with the community leaders, structured interview with the volunteers, and records and reports analysis.</p> <p>Results and discussion</p> <p>The overall adherence of volunteers to the project protocol in treating and referring cases was accepted that was only one of the 20 volunteers did not comply with the study guidelines. Although the use of RDTs seemed to have improved the level of accuracy and trust in the diagnosis, 30% of volunteers did not rely on the negative RDT results when treating fever cases. Almost all (94.7%) the volunteers felt that they were satisfied with the spiritual outcome of their new tasks. As well, volunteers have initiated advocacy campaigns supported by their village health committees which were found to have a positive role to play in the project that proved their acceptability of the HMM design. The planned system for supply was found to be effective. The project was found to improve the accessibility to ACTs from 25% to 64.7% and the treatment seeking behaviour from 83.3% to 100% before- and after the HMM implementation respectivly.</p> <p>Conclusion</p> <p>The evaluation of the project identified the feasibility of the planned model in Sudan's condition. Moreover, the communities as well as the volunteers found to be satisfied with and supportive to the system and the outcome. The problem of treating other febrile cases when diagnosis is not malaria and other non-fever cases needs to be addressed as well.</p

Progress towards implementation of ACT malaria case-management in public health facilities in the Republic of Sudan: a cluster-sample survey

<p>Abstract</p> <p>Background</p> <p>Effective malaria case-management based on artemisinin-based combination therapy (ACT) and parasitological diagnosis is a major pillar within the 2007-2012 National Malaria Strategic Plan in the Sudan. Three years after the launch of the strategy a health facility survey was undertaken to evaluate case-management practices and readiness of the health facilities and health workers to implement a new malaria case-management strategy.</p> <p>Methods</p> <p>A cross-sectional, cluster sample survey was undertaken at public health facilities in 15 states of Sudan. Data were collected using quality-of-care assessment methods. The main outcomes were the proportions of facilities with ACTs and malaria diagnostics; proportions of health workers exposed to malaria related health systems support activities; and composite and individual indicators of case-management practices for febrile outpatients stratified by age, availability of ACTs and diagnostics, use of malaria diagnostics, and test result.</p> <p>Results</p> <p>We evaluated 244 facilities, 294 health workers and 1,643 consultations for febrile outpatients (425 < 5 years and 1,218 ≥ 5 years). Health facility and health worker readiness was variable: chloroquine was available at only 5% of facilities, 73% stocked recommended artesunate and sulfadoxine/pyrimethamine (AS+SP), 51% had the capacity to perform parasitological diagnosis, 53% of health workers had received in-service training on ACTs, 24% were trained in the use of malaria Rapid Diagnostic Tests, and 19% had received a supervisory visit including malaria case-management. At all health facilities 46% of febrile patients were parasitologically tested and 35% of patients were both, tested and treated according to test result. At facilities where AS+SP and malaria diagnostics were available 66% of febrile patients were tested and 51% were both, tested and treated according to test result. Among test positive patients 64% were treated with AS+SP but 24% were treated with artemether monotherapy. Among test negative patients only 17% of patients were treated for malaria. The majority of ACT dispensing and counseling practices were suboptimal.</p> <p>Conclusions</p> <p>Five years following change of the policy from chloroquine to ACTs and 3 years before the end of the new malaria strategic plan chloroquine was successfully phased out from public facilities in Sudan, however, an important gap remained in the availability of ACTs, diagnostic capacities and coverage with malaria case-management activities. The national scale-up of diagnostics, using the findings of this survey as well as future qualitative research, should present an opportunity not only to expand existing testing capacities but also to implement effective support interventions to bridge the health systems gaps and support corrective case-management measures, including the discontinuation of artemether monotherapy treatment.</p

Clinical and biological significance of RAD51 expression in breast cancer: a key DNA damage response protein

Impaired DNA damage response (DDR) may play a fundamental role in the pathogenesis of breast cancer (BC). RAD51 is a key player in DNA double-strand break repair. In this study, we aimed to assess the biological and clinical significance of RAD51 expression with relevance to different molecular classes of BC and patients’ outcome. The expression of RAD51 was assessed immunohistochemically in a well-characterised annotated series (n = 1184) of early-stage invasive BC with long-term follow-up. A subset of cases of BC from patients with known BRCA1 germline mutations was included as a control group. The results were correlated with clinicopathological and molecular parameters and patients’ outcome. RAD51 protein expression level was also assayed in a panel of cell lines using reverse phase protein array (RPPA). RAD51 was expressed in the nuclei (N) and cytoplasm (C) of malignant cells. Subcellular colocalisation phenotypes of RAD51 were significantly associated with clinicopathological features and patient outcome. Cytoplasmic expression (RAD51C+) and lack of nuclear expression (RAD51 N-) were associated with features of aggressive behaviour, including larger tumour size, high grade, lymph nodal metastasis, basal-like, and triple-negative phenotypes, together with aberrant expression of key DDR biomarkers including BRCA1. All BRCA1-mutated tumours had RAD51C+/N- phenotype. RPPA confirmed IHC results and showed differential expression of RAD51 in cell lines based on ER expression and BRCA1 status. RAD51 N+ and RAD51C+ tumours were associated with longer and shorter breast cancer-specific survival (BCSS), respectively. The RAD51 N+ was an independent predictor of longer BCSS (P<0.0001). Lack of RAD51 nuclear expression is associated with poor prognostic parameters and shorter survival in invasive BC patients. The significant associations between RAD51 subcellular localisation and clinicopathological features, molecular subtype and patients’ outcome suggest that the trafficking of DDR proteins between the nucleus and cytoplasm might play a role in the development and progression of BC

Long-term follow-up of glycemic and neurological outcomes in an international series of patients with sulfonylurea-treated ABCC8 permanent neonatal diabetes

This is the author accepted manuscript. The final version is available from the American Diabetes Association via the DOI in this record OBJECTIVE ABCC8 mutations cause neonatal diabetes mellitus that can be transient (TNDM) or, less commonly, permanent (PNDM); ∼90% of individuals can be treated with oral sulfonylureas instead of insulin. Previous studies suggested that people with ABCC8-PNDM require lower sulfonylurea doses and have milder neurological features than those with KCNJ11-PNDM. However, these studies were short-term and included combinations of ABCC8-PNDM and ABCC8-TNDM. We aimed to assess the long-term glycemic and neurological outcomes in sulfonylurea-treated ABCC8-PNDM. RESEARCH DESIGN AND METHODS We studied all 24 individuals with ABCC8-PNDM diagnosed in the U.K., Italy, France, and U.S. known to transfer from insulin to sulfonylureas before May 2010. Data on glycemic control, sulfonylurea dose, adverse effects including hypoglycemia, and neurological features were analyzed using nonparametric statistical methods. RESULTS Long-term data were obtained for 21 of 24 individuals (median follow-up 10.0 [range 4.1–13.2] years). Eighteen of 21 remained on sulfonylureas without insulin at the most recent follow-up. Glycemic control improved on sulfonylureas (presulfonylurea vs. 1-year posttransfer HbA1c 7.2% vs. 5.7%, P = 0.0004) and remained excellent long-term (1-year vs. 10-year HbA1c 5.7% vs. 6.5%, P = 0.04), n = 16. Relatively high doses were used (1-year vs. 10-year dose 0.37 vs. 0.25 mg/kg/day glyburide, P = 0.50) without any severe hypoglycemia. Neurological features were reported in 13 of 21 individuals; these improved following sulfonylurea transfer in 7 of 13. The most common features were learning difficulties (52%), developmental delay (48%), and attention deficit hyperactivity disorder (38%). CONCLUSIONS Sulfonylurea treatment of ABCC8-PNDM results in excellent long-term glycemic control. Overt neurological features frequently occur and may improve with sulfonylureas, supporting early, rapid genetic testing to guide appropriate treatment and neurodevelopmental assessment.Wellcome Trus