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Article ; Online: Editorial: Neuroimmunology in Africa.

Masocha, Willias / Idro, Richard / Furlan, Roberto / Lakhdar-Ghazal, Nouria

2023 Volume 14, Page(s) 1201494

MeSH term(s)	Humans ; Cytokines ; Inflammation ; Africa
Chemical Substances	Cytokines
Language	English
Publishing date	2023-05-02
Publishing country	Switzerland
Document type	Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1201494
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Article ; Online: Ketogenic dietary therapy utilization in Kenya: A qualitative exploration of dietitian's perceptions.

Samia, Pauline / Naanyu, Violet / Helen Cross, J / Idro, Richard / Boon, Paul / Wilmshurst, Jo / Luchters, Stanley

Epilepsy & behavior reports

2024 Volume 26, Page(s) 100661

Abstract: This study utilized a qualitative design to explore dietitians' perceptions regarding Ketogenic Diet Therapy (KDT) for patients with drug-resistant epilepsy in Kenya. Dietitians from Kenya were selected and consented. Audio-recorded interviews were ... ...

Abstract	This study utilized a qualitative design to explore dietitians' perceptions regarding Ketogenic Diet Therapy (KDT) for patients with drug-resistant epilepsy in Kenya. Dietitians from Kenya were selected and consented. Audio-recorded interviews were conducted, followed by thematic analysis of verbatim transcripts to identify recurring patterns. The study enrolled 18 dietitians, fourteen of whom correctly described their understanding of KDT for managing drug-resistant epilepsy. There was a lack of confidence in their capacity to initiate the KDT with all expressing the need for further training and facilitation. Only one dietitian reported having initiated and maintained KDT. There was an overall positive view regarding KDT and willingness to implement KDT for patients with drug-resistant epilepsy. Dietitians expressed concerns regarding the availability of national policies, inadequate staffing to support families who require KDT, and the cost of implementing this intervention. Dietitians expressed interest in virtual training to enhance their understanding of KDT. Dietitians in Kenya are mostly aware of KDT utilization for the management of drug-resistant epilepsy. However, they cited poor capability and various barriers to implementation. There is a need for policies to facilitate KDT as a treatment option for the benefit of patients with drug-resistant epilepsy.
Language	English
Publishing date	2024-03-20
Publishing country	United States
Document type	Journal Article
ISSN	2589-9864
ISSN (online)	2589-9864
DOI	10.1016/j.ebr.2024.100661
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Article ; Online: Neuroimmunology of Common Parasitic Infections in Africa.

Idro, Richard / Ogwang, Rodney / Barragan, Antonio / Raimondo, Joseph Valentino / Masocha, Willias

Frontiers in immunology

2022 Volume 13, Page(s) 791488

Abstract: Parasitic infections of the central nervous system are an important cause of morbidity and mortality in Africa. The neurological, cognitive, and psychiatric sequelae of these infections result from a complex interplay between the parasites and the host ... ...

Abstract	Parasitic infections of the central nervous system are an important cause of morbidity and mortality in Africa. The neurological, cognitive, and psychiatric sequelae of these infections result from a complex interplay between the parasites and the host inflammatory response. Here we review some of the diseases caused by selected parasitic organisms known to infect the nervous system including
MeSH term(s)	Animals ; Parasites/physiology ; Parasitic Diseases/epidemiology ; Plasmodium falciparum ; Toxoplasma/physiology ; Trypanosoma brucei brucei
Language	English
Publishing date	2022-02-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.791488
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Article: Prevalence and risk factors of gross neurologic deficits in children after severe malaria: a systematic review protocol.

Okullo, Allen Eva / John, Chandy C / Idro, Richard / Conroy, Andrea L / Kinengyere, Alison Annet / Ojiambo, Kevin Ouma / Otike, Caroline / Ouma, Simple / Ocan, Moses / Obuku, Ekwaro A / van Hensbroek, Michaël Boele

Research square

2024

Abstract: Background: Children exposed to severe malaria may recover with gross neurologic deficits (GND). Several risk factors for GND after cerebral malaria (CM), the deadliest form of severe malaria, have been identified in children. However, there is ... ...

Abstract	Background: Children exposed to severe malaria may recover with gross neurologic deficits (GND). Several risk factors for GND after cerebral malaria (CM), the deadliest form of severe malaria, have been identified in children. However, there is inconsistency between previously reported and more recent findings. Although CM patients are the most likely group to develop GND, it is not clear if other forms of severe malaria (non-CM) may also contribute to the malaria related GND. The aim of this systematic review is to synthesize evidence on the prevalence and risk factors for GND in children following CM and map the changes in patterns over time. In addition, this review will synthesize evidence on the reported prevalence and risk factors of gross neurologic deficits following other forms of severe malaria. Methods: The systematic review will be conducted according to recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols (PRISMA-P). Relevant research articles will be identified using relevant search terms from the following databases: MEDLINE, Embase, Web of Science and Global Index Medicus (GIM). The articles will be screened at title and abstract, then at full text for inclusion using Discussion: Findings from this systematic review will inform policy makers on planning, design and implementation of interventions targeting the treatment and rehabilitation of GND following severe malaria in children. Systematic review registration: The protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42022297109.
Language	English
Publishing date	2024-02-23
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3374025/v1
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Article ; Online: Bi-isotype immunoglobulins enhance antibody-mediated neutrophil activity against

Ogwang, Rodney / Murugu, Lewis / Nkumama, Irene N / Nyamako, Lydia / Kai, Oscar / Mwai, Kennedy / Murungi, Linda / Idro, Richard / Bejon, Philip / Tuju, James / Kinyanjui, Sam Muchina / Osier, Faith H A

Frontiers in immunology

2024 Volume 15, Page(s) 1360220

Abstract: Background: Malaria remains a major global health priority, and monoclonal antibodies (mAbs) are emerging as potential new tools to support efforts to control the disease. Recent data suggest that Fc-dependent mechanisms of immunity are important ... ...

Abstract	Background: Malaria remains a major global health priority, and monoclonal antibodies (mAbs) are emerging as potential new tools to support efforts to control the disease. Recent data suggest that Fc-dependent mechanisms of immunity are important mediators of protection against the blood stages of the infection, but few studies have investigated this in the context of mAbs. We aimed to isolate mAbs agnostic to cognate antigens that target whole merozoites and simultaneously induce potent neutrophil activity measured by the level of reactive oxygen species (ROS) production using an antibody-dependent respiratory burst (ADRB) assay. Methods: We used samples from semi-immune adults living in coastal Kenya to isolate mAbs that induce merozoite-specific ADRB activity. We then tested whether modifying the expressed IgG1 isotype to an IgG-IgA Fc region chimera would enhance the level of ADRB activity. Results: We isolated a panel of nine mAbs with specificity to whole merozoites. mAb J31 induced ADRB activity in a dose-dependent fashion. Compared to IgG1, our modified antibody IgG-IgA bi-isotype induced higher ADRB activity across all concentrations tested. Further, we observed a negative hook effect at high IgG1 mAb concentrations (i.e., >200 µg/mL), but this was reversed by Fc modification. We identified MSP3.5 as the potential cognate target of mAb J31. Conclusions: We demonstrate an approach to engineer mAbs with enhanced ADRB potency against blood-stage parasites.
Language	English
Publishing date	2024-04-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1360220
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Article: Neurocognitive Impairment in Ugandan Children with Sickle Cell Anemia Compared to Sibling Controls: A cross-sectional study.

Bangirana, Paul / Boehme, Amelia K / Birabwa, Annet / Opoka, Robert O / Munube, Deogratias / Mupere, Ezekiel / Kasirye, Phillip / Muwanguzi, Grace / Musiimenta, Maxencia / Ru, George / Green, Nancy S / Idro, Richard

medRxiv : the preprint server for health sciences

2024

Abstract: Introduction: Neurocognitive function in Ugandan children aged 1-12 years with sickle cell anemia (SCA) were compared to their non-SCA siblings to identify risk factors for disease-associated impairment.: Methods: This cross-sectional neurocognitive ... ...

Abstract	Introduction: Neurocognitive function in Ugandan children aged 1-12 years with sickle cell anemia (SCA) were compared to their non-SCA siblings to identify risk factors for disease-associated impairment. Methods: This cross-sectional neurocognitive function study of children with SCA (N=242) and non-SCA siblings (N=127) used age- and linguistically-appropriate standardized tests of cognition, executive function and attention for children ages 1-4 and 5-12 years. Test scores were converted to locally derived age-normalized z-scores. The SCA group underwent standardized stroke examination for prior stroke and transcranial doppler ultrasound (TCD) to determine stroke risk by arterial flow velocity. Results: The SCA group was younger than siblings (mean ages 5.46±3.0 versus 7.11±3.51 years, respectively; p <.001), with lower hemoglobin concentration (7.32±1.02 vs. 12.06±1.42, p <.001). Overall cognitive SCA z-scores were lower: -0.73 ±0.98 vs. siblings -0.25 ±1.12 (p<.001), with comparable findings for executive function of -1.09±0.94 versus -0.84±1.26 (p=0.045), respectively. Attention z-scores for ages 5-12 for the SCA group and controls were similar: -0.37±1.4 vs. -0.11±0.17 (p=.09). Overall differences by SCA status were largely driven by the older age group, as z-scores in the younger sub-sample did not differ from controls. Analyses revealed the strongest predictors of poor neurocognitive outcomes among the SCA sample to be the disease, age and prior stroke (each p<.001). Impact from anemia and SCA were indistinguishable. Discussion: Neurocognitive testing in children with SCA compared to non-SCA siblings revealed poorer SCA-associated functioning in children older than age 4. Results indicate need for trials assessing impact from disease modification for children with SCA.
Language	English
Publishing date	2024-01-29
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.09.23298329
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Article: Hydroxyurea Therapy for Neurological and Cognitive Protection in Pediatric Sickle Cell Anemia in Uganda (BRAIN SAFE II): Protocol for a single-arm open label trial.

Mboizi, Vincent / Nabaggala, Catherine / Munube, Deogratias / Ssenkusu, John M / Kasirye, Phillip / Kamya, Samson / Kawooya, Michael G / Boehme, Amelia / Minja, Frank / Mupere, Ezekiel / Opoka, Robert / Rosano, Caterina / Green, Nancy S / Idro, Richard

medRxiv : the preprint server for health sciences

2024

Abstract: Background: Children with sickle cell anemia (SCA) in Sub-Saharan Africa are at high risk of sickle cerebrovascular injury (SCVI). Hydroxyurea, a commonly used disease-modifying therapy, may prevent or decrease SCVI for reduced incident stroke, stroke ... ...

Abstract	Background: Children with sickle cell anemia (SCA) in Sub-Saharan Africa are at high risk of sickle cerebrovascular injury (SCVI). Hydroxyurea, a commonly used disease-modifying therapy, may prevent or decrease SCVI for reduced incident stroke, stroke risk and potentially cognitive dysfunction. We aim to test the impact of daily hydroxyurea therapy on these outcomes in Ugandan children with SCA. We hypothesize that hydroxyurea therapy over 36 months will prevent, stabilize or improve these complications of SCA. Methods: The BRAIN SAFE II study is an open-label, single-arm trial of daily hydroxyurea for 270 children with SCA (HbSS) in Uganda, ages 3-9 years. Following baseline assessments, participants began hydroxyurea therapy and clinically followed per local guidelines. Standard hydroxyurea dose is escalated to maximum tolerated dose (MTD). SCVI is assessed by cerebral arterial velocity using Doppler ultrasound, with cognitive function determined by formal neurocognitive testing (primary outcomes). Structural SCVI is assessed by magnetic resonance imaging (MRI) and angiography (MRA) in a sub-sample of 90 participants ages ≥5 years, along with biomarkers of anemia, inflammation and malnutrition (secondary outcomes). At trial midpoint (18 months) and completion (36 months), primary outcomes will be compared to participants' baseline to determine hydroxyurea impact and relationships to secondary outcomes. Conclusion: This open-label, single-arm trial will examine the impact of hydroxyurea on preventing or ameliorating SCA SCVI in children, assessed by reducing incident stroke, stroke risk and neurocognitive dysfunction. Trial results will provide important insight into the role of hydroxyurea therapy on critical manifestations of SCVI in children with SCA.
Language	English
Publishing date	2024-01-13
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.12.24301208
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Article ; Online: Chronic pain among children with cerebral palsy attending a Ugandan tertiary hospital: a cross-sectional study.

Bambi, Emma Nsalazi / Mwesige, Angelina Kakooza / Lekuya, Hervé Monka / Kasirye, Philip / Idro, Richard

BMC pediatrics

2021 Volume 21, Issue 1, Page(s) 456

Abstract: Background: Children with cerebral palsy (CP) frequently experience chronic pain. The burden and severity of such pain is often underestimated in relation to their other impairments. Recognition and awareness of this chronic pain among children with CP ... ...

Abstract	Background: Children with cerebral palsy (CP) frequently experience chronic pain. The burden and severity of such pain is often underestimated in relation to their other impairments. Recognition and awareness of this chronic pain among children with CP constitute the cornerstone for caretakers and clinicians to improve the quality of life of those children. This study aimed to determine the prevalence of chronic pain among children with CP, and the factors associated. Methods: A cross-sectional study of children with CP, aged 2-12 years, attending the CP rehabilitation clinic and Pediatric Neurology Clinic at Mulago Hospital, Uganda from November 2017 to May 2018. A detailed history and clinical examination were performed and the co-morbidities were determined. CP was classified using the Gross Motor Function Classification System (GMFCS), Manual Ability Classification System, Communication Function Classification System (CFCS), and the Eating and Drinking Ability Classification System (EDACS) and documented with the level of impairment in the different domains. Pain was assessed by using the revised Face, Legs, Activity, Consolability, Cry pain scale. Results: A total of 224 children with CP were enrolled. The prevalence of chronic pain was 64.3%. The majority had spastic bilateral CP (77.8%), moderate pain lasting over 6 months, and none of them was on long-term pain management. Epilepsy (60.9%), behavioral problem (63.2%), hearing impairment (66,7%), learning problem (67,6%), dental caries (75%), gastro-esophageal reflux (75%), sleep disorders (79.5%), vision impairment (80%), and malnutrition (90%) were co- morbid conditions of chronic pain in children with CP in this study. The factors independently associated with chronic pain among children with CP were the GMFCS level IV & V, CFCS level IV & V, EDACS level IV & V, female children, and caretaker aged more than 30 years. Conclusions: Two-thirds of children with CP attending rehabilitation in this hospital had chronic pain. None was receiving pain management. Chronic pain was associated with the presence of multiple co-morbidities and more severe disability. Rehabilitation and care programs for children with CP should include assessment of pain in routine care and provide interventions for pain relief in children with CP even at an early age.
MeSH term(s)	Cerebral Palsy/complications ; Cerebral Palsy/epidemiology ; Child ; Chronic Pain/epidemiology ; Chronic Pain/etiology ; Cross-Sectional Studies ; Dental Caries ; Female ; Humans ; Quality of Life ; Severity of Illness Index ; Tertiary Care Centers ; Uganda/epidemiology
Language	English
Publishing date	2021-10-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2041342-7
ISSN	1471-2431 ; 1471-2431
ISSN (online)	1471-2431
ISSN	1471-2431
DOI	10.1186/s12887-021-02928-1
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Article ; Online: Vitamin D status and associated factors among HIV-infected children and adolescents on antiretroviral therapy in Kampala, Uganda.

Piloya, Thereza Were / Bakeera-Kitaka, Sabrina / Kisitu, Grace Paul / Idro, Richard / Cusick, Sarah E

PloS one

2021 Volume 16, Issue 6, Page(s) e0253689

Abstract: Background: A high prevalence of suboptimal serum vitamin D has been reported among HIV infected children even in countries with high sunshine abundance throughout the year. Vitamin D is a potent immune modulator of innate and adaptive immune responses. ...

Abstract	Background: A high prevalence of suboptimal serum vitamin D has been reported among HIV infected children even in countries with high sunshine abundance throughout the year. Vitamin D is a potent immune modulator of innate and adaptive immune responses. Vitamin D regulates immune responses through the vitamin D receptor on CD4 cells. We aimed to determine the vitamin D status of HIV infected children and factors associated with suboptimal vitamin D. Methods: This was a cross sectional study. We enrolled children aged between 6 months and 12 years attending an outpatient paediatric HIV clinic. Serum 25-hydroxyvitamin D (25(OH)D) was measured using the electrochemoluminisence method. Suboptimal vitamin D was defined as 25(OH)D <30 ng/ml, vitamin D insufficiency and deficiency were 21-29 ng/ml and <20 ng/ml respectively. Anthropometry, physical exam and medical history were documented. Logistic regression was performed. Results: We enrolled 376 children with mean age (sd) 8.05 years (3.03), a median (IQR) duration of ART of 5.9 years (3.2-8.4). Majority of the children (64%) had been exposed to non nucleoside reverse transcriptase inhibitors (NNRTIs). A third were severely immunosuppressed (CD4% ≤15%) at ART initiation. At the time of the study, the majority (89%) were virologically suppressed (VL <1000 copies/ml). Prevalence of 25(OH)D <30 ng/ml was 49 (13%) of 375 participants and 11 (3%) had 25(OH)D <20 ng/ml. Lopinavir/ritonavir regimen was independently associated with 25(OH)D <30 ng/ml; OR 0.27 CI (0.13-0.57), p value-0.002. Serum 25(OH)D <20 ng/ml was associated with CD4 count ≤15% at ART initiation OR 6.55(1.30-32.9), p value-0.023 and use of NNRTIs; OR 10.9(1.22-96.2), p value-0.03. Conclusion: We found a low prevalence of suboptimal vitamin D compared to earlier reports. Severe immunosuppression at ART initiation and use of NNRTIs increases odds of deficiency. Vitamin D supplementation should be considered in severely immunosuppressed children initiating ART.
MeSH term(s)	Calcifediol/blood ; Child ; Child, Preschool ; Female ; HIV Infections/blood ; HIV Infections/drug therapy ; HIV Infections/epidemiology ; HIV-1/metabolism ; Humans ; Infant ; Lopinavir/administration & dosage ; Male ; Ritonavir/administration & dosage ; Uganda/epidemiology ; Vitamin D Deficiency/blood ; Vitamin D Deficiency/drug therapy ; Vitamin D Deficiency/epidemiology
Chemical Substances	Lopinavir (2494G1JF75) ; Ritonavir (O3J8G9O825) ; Calcifediol (P6YZ13C99Q)
Language	English
Publishing date	2021-06-24
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0253689
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Article ; Online: Health related quality of life in children with spina bifida in Uganda.

Bannink, Femke / Idro, Richard / Van Hove, Geert

Disability and health journal

2018 Volume 11, Issue 4, Page(s) 650–654

Abstract: Background: Studies on health related quality of life (HRQOL) of children with disabilities in low income countries are limited.: Objective: To inform interventions for children with spina bifida in low income countries, HRQOL of children with spina ... ...

Abstract	Background: Studies on health related quality of life (HRQOL) of children with disabilities in low income countries are limited. Objective: To inform interventions for children with spina bifida in low income countries, HRQOL of children with spina bifida and siblings, predictors, relationships between HRQOL and parental stress in Uganda were examined. Methods: Demographic, impairment, daily, social functioning data, and HRQOL using the KIDSCREEN-10 were collected from 39 children, 33 siblings, and 39 parents from a cohort of families of children with spina bifida. T-tests, correlations, analysis of variance and regression analysis were used to compare means between children with spina bifida and their siblings, understand relationships between variables, and identify predictors of HRQOL. Results: Children with spina bifida (N = 39) had lower HRQOL compared to their siblings (N = 33) (t = -3.868, p < .001 parental; t = -3.248, p = .002 child ratings). Parents (N = 39) indicated higher parental stress for their child with spina bifida (t = 2.143, p = 0.036). HRQOL child outcomes were predicted by the presence of hydrocephalus (β = -.295, p = 0.013) for children with spina bifida, and daily functioning levels (β = .336, p = 0.038), and parental support (β = .357, p = 0.041) for siblings specifically. Parent rated HRQOL outcomes were predicted by parental distress (β = -.337, p = 0.008), incontinence (β = .423, p = 0.002), and daily functioning levels (β = .325, p = 0.016) for children with spina bifida. Conclusions: To improve HRQOL investment in neurosurgical care, community based rehabilitation, incontinence management, and parental support are required. A combination of child friendly semi-structured and creative research methods are recommended to study HRQOL.
MeSH term(s)	Adult ; Child ; Disabled Children/psychology ; Disabled Children/statistics & numerical data ; Female ; Humans ; Male ; Middle Aged ; Parents/psychology ; Quality of Life/psychology ; Siblings/psychology ; Spinal Dysraphism/psychology ; Surveys and Questionnaires ; Uganda
Language	English
Publishing date	2018-04-03
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2414615-8
ISSN	1876-7583 ; 1936-6574
ISSN (online)	1876-7583
ISSN	1936-6574
DOI	10.1016/j.dhjo.2018.03.008
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