The Ethnomedicine of the Haya people of Bugabo ward, Kagera Region, north western Tanzania

\ud The Kagera region, in north western Tanzania, is endowed with a strong culture of traditional medicine that is well supported by a rich diversity of medicinal plants. However, most of the plants in this region have not been documented nor evaluated for safety and efficacy. As an initiative in that direction, this study documented the knowledge on medicinal plant use by traditional healers of Bugabo Ward in Bukoba District. Key informants were selected with the help of local government officials and information on their knowledge and use of plants for therapeutic purposes was gathered using a semi-structured interview format. In this study 94 plant species representing 84 genera and 43 families were found to be commonly used in the treatment of a variety of human ailments. The family Asteraceae had the highest number of species being used as traditional medicines. The study revealed that Malaria is treated using the highest number of different medicinal species (30), followed by skin conditions (19), maternal illnesses and sexually transmitted diseases (14), respiratory diseases (11) and yellow fever, Herpes simplex and peptic ulcers (10). Majority of the species are used to treat less than five different diseases/conditions each and leaves were the most commonly used part, comprising 40% of all the reports on use of plant parts. Trees comprised the most dominant growth form among all plants used for medicinal purposes in the study area. Bugabo Ward has a rich repository of medicinal plants and this reinforces the need for an extensive and comprehensive documentation of medicinal plants in the area and a concomitant evaluation of their biological activity as a basis for developing future medicines.\u

Medulloblastoma outcome is adversely associated with overexpression of EEF1D, RPL30, and RPS20 on the long arm of chromosome 8

BACKGROUND: Medulloblastoma is the most common malignant brain tumor of childhood. Improvements in clinical outcome require a better understanding of the genetic alterations to identify clinically significant biological factors and to stratify patients accordingly. In the present study, we applied cytogenetic characterization to guide the identification of biologically significant genes from gene expression microarray profiles of medulloblastoma. METHODS: We analyzed 71 primary medulloblastomas for chromosomal copy number aberrations (CNAs) using comparative genomic hybridization (CGH). Among 64 tumors that we previously analyzed by gene expression microarrays, 27 were included in our CGH series. We analyzed clinical outcome with respect to CNAs and microarray results. We filtered microarray data using specific CNAs to detect differentially expressed candidate genes associated with survival. RESULTS: The most frequent lesions detected in our series involved chromosome 17; loss of 16q, 10q, or 8p; and gain of 7q or 2p. Recurrent amplifications at 2p23-p24, 2q14, 7q34, and 12p13 were also observed. Gain of 8q is associated with worse overall survival (p = 0.0141), which is not entirely attributable to MYC amplification or overexpression. By applying CGH results to gene expression analysis of medulloblastoma, we identified three 8q-mapped genes that are associated with overall survival in the larger group of 64 patients (p < 0.05): eukaryotic translation elongation factor 1D (EEF1D), ribosomal protein L30 (RPL30), and ribosomal protein S20 (RPS20). CONCLUSION: The complementary use of CGH and expression profiles can facilitate the identification of clinically significant candidate genes involved in medulloblastoma growth. We demonstrate that gain of 8q and expression levels of three 8q-mapped candidate genes (EEF1D, RPL30, RPS20) are associated with adverse outcome in medulloblastoma

Medulloblastomas overexpress the p53-inactivating oncogene WIP1/PPM1D

Medulloblastoma is the most common malignant brain tumor of childhood. Despite numerous advances, clinical challenges range from recurrent and progressive disease to long-term toxicities in survivors. The lack of more effective, less toxic therapies results from our limited understanding of medulloblastoma growth. Although TP53 is the most commonly altered gene in cancers, it is rarely mutated in medulloblastoma. Accumulating evidence, however, indicates that TP53 pathways are disrupted in medulloblastoma. Wild-typep53-induced phosphatase 1 (WIP1 or PPM1D) encodes a negative regulator of p53. WIP1 amplification (17q22-q23) and its overexpression have been reported in diverse cancer types. We examined primary medulloblastoma specimens and cell lines, and detected WIP1 copy gain and amplification prevalent among but not exclusively in the tumors with 17q gain and isochromosome 17q (i17q), which are among the most common cytogenetic lesions in medulloblastoma. WIP1 RNA levels were significantly higher in the tumors with 17q gain or i17q. Immunoblots confirmed significant WIP1 protein in primary tumors, generally higher in those with 17q gain or i17q. Under basal growth conditions and in response to the chemotherapeutic agent, etoposide, WIP1 antagonized p53-mediated apoptosis in medulloblastoma cell lines. These results indicate that medulloblastoma express significant levels of WIP1 that modulate genotoxic responsiveness by negatively regulating p53

In vitro neuroprotective potential of four medicinal plants against rotenone-induced toxicity in SH-SY5Y neuroblastoma cells

BACKGROUND: Lannea schweinfurthii, Zanthoxylum capense, Scadoxus puniceus and Crinum bulbispermum are used traditionally to treat neurological disorders. The aim of this study was to evaluate the cytoprotective potential of the four plants, after induction of toxicity using rotenone, in SH-SY5Y neuroblastoma cells. METHODS: Cytotoxicity of the plant extracts and rotenone was assessed using the sulforhodamine B (SRB) assay. Fluorometry was used to measure intracellular redox state (reactive oxygen species (ROS) and intracellular glutathione content), mitochondrial membrane potential (MMP) and caspase-3 activity, as a marker of apoptotic cell death. RESULTS: Of the tested plants, the methanol extract of Z. capense was the least cytotoxic; LC(50) 121.3 ± 6.97 μg/ml, while S. puniceus methanol extract was the most cytotoxic; LC(50) 20.75 ± 1.47 μg/ml. Rotenone reduced intracellular ROS levels after 24 h exposure. Pre-treating cells with S. puniceus and C. bulbispermum extracts reversed the effects of rotenone on intracellular ROS levels. Rotenone exposure also decreased intracellular glutathione levels, which was counteracted by pre-treatment with any one of the extracts. MMP was reduced by rotenone, which was neutralized by pre-treatment with C. bulbispermum ethyl acetate extract. All extracts inhibited rotenone-induced activation of caspase-3. CONCLUSION: The studied plants demonstrated anti-apoptotic activity and restored intracellular glutathione content following rotenone treatment, suggesting that they may possess neuroprotective properties

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global, regional, and national burden of other musculoskeletal disorders, 1990-2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021

Background Musculoskeletal disorders include more than 150 different conditions affecting joints, muscles, bones, ligaments, tendons, and the spine. To capture all health loss from death and disability due to musculoskeletal disorders, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) includes a residual musculoskeletal category for conditions other than osteoarthritis, rheumatoid arthritis, gout, low back pain, and neck pain. This category is called other musculoskeletal disorders and includes, for example, systemic lupus erythematosus and spondylopathies. We provide updated estimates of the prevalence, mortality, and disability attributable to other musculoskeletal disorders and forecasted prevalence to 2050. Methods Prevalence of other musculoskeletal disorders was estimated in 204 countries and territories from 1990 to 2020 using data from 68 sources across 23 countries from which subtraction of cases of rheumatoid arthritis, osteoarthritis, low back pain, neck pain, and gout from the total number of cases of musculoskeletal disorders was possible. Data were analysed with Bayesian meta-regression models to estimate prevalence by year, age, sex, and location. Years lived with disability (YLDs) were estimated from prevalence and disability weights. Mortality attributed to other musculoskeletal disorders was estimated using vital registration data. Prevalence was forecast to 2050 by regressing prevalence estimates from 1990 to 2020 with Socio-demographic Index as a predictor, then multiplying by population forecasts. Findings Globally, 494 million (95% uncertainty interval 431–564) people had other musculoskeletal disorders in 2020, an increase of 123·4% (116·9–129·3) in total cases from 221 million (192–253) in 1990. Cases of other musculoskeletal disorders are projected to increase by 115% (107–124) from 2020 to 2050, to an estimated 1060 million (95% UI 964–1170) prevalent cases in 2050; most regions were projected to have at least a 50% increase in cases between 2020 and 2050. The global age-standardised prevalence of other musculoskeletal disorders was 47·4% (44·9–49·4) higher in females than in males and increased with age to a peak at 65–69 years in male and female sexes. In 2020, other musculoskeletal disorders was the sixth ranked cause of YLDs globally (42·7 million [29·4–60·0]) and was associated with 83 100 deaths (73 600–91 600). Interpretation Other musculoskeletal disorders were responsible for a large number of global YLDs in 2020. Until individual conditions and risk factors are more explicitly quantified, policy responses to this burden remain a challenge. Temporal trends and geographical differences in estimates of non-fatal disease burden should not be overinterpreted as they are based on sparse, low-quality data. Funding Bill & Melinda Gates Foundation