Fisetin induces G2/M phase arrest and caspase-mediated cleavage of p21Cip1 and p27Kip1 leading to apoptosis and tumor growth inhibition in HNSCC.

The anticancer potential and associated mechanisms of flavonoid fisetin are yet to be fully investigated on human head and neck squamous cell carcinoma (HNSCC). In the present study, fisetin (25-75 µM for 24-48 h) dose-dependently inhibited growth and induced death in HNSCC Cal33 and UM-SCC-22B cells, without showing any death in normal cells. Fisetin (25-50 µM) induced G2/M phase arrest via decrease in Cdc25C, CDK1, cyclin B1 expression, and an increase in p53(S15). A concentration-dependent increase in fisetin-induced DNA damage and apoptosis in HNSCC cells was authenticated by comet assay, gamma-H2A.X(S139) phosphorylation, and marked cleavage of PARP protein. Interestingly, fisetin-induced cell death occurred independently of p53 and reactive oxygen species production. The activation of JNK and inhibition of PI3K/Akt, ERK1/2, EGFR, and STAT-3 signaling were identified. Further, fisetin-induced apoptosis was mediated, in part, via p21Cip1 and p27Kip1 cleavage by caspase, which was reversed by z-VAD-FMK, a pan-caspase inhibitor. Subsequently, fisetin was also found to induce autophagy; nevertheless, autophagy attenuation exaggerated apoptosis. Oral fisetin (50 mg/kg body weight) treatment to establish Cal33 xenograft in mice for 19 days showed 73% inhibition in tumor volume (p < 0.01) along with a decrease in Ki67-positive cells and an increase in cleaved caspase-3 level in tumors. Consistent with the effect of 50 µM fisetin in vitro, the protein levels of p21Cip1 and P27Kip1 were also decreased by fisetin in tumors. Together, these findings showed strong anticancer efficacy of fisetin against HNSCC with downregulation of EGFR-Akt/ERK1/2-STAT-3 pathway and activation of JNK/c-Jun, caspases and caspase-mediated cleavage of p21Cip1 and p27Kip1.

Breast cancer risk prediction using machine learning: a systematic review.

Background: Breast cancer is the leading cause of cancer-related fatalities among women worldwide. Conventional screening and risk prediction models primarily rely on demographic and patient clinical history to devise policies and estimate likelihood. However, recent advancements in artificial intelligence (AI) techniques, particularly deep learning (DL), have shown promise in the development of personalized risk models. These models leverage individual patient information obtained from medical imaging and associated reports. In this systematic review, we thoroughly investigated the existing literature on the application of DL to digital mammography, radiomics, genomics, and clinical information for breast cancer risk assessment. We critically analyzed these studies and discussed their findings, highlighting the promising prospects of DL techniques for breast cancer risk prediction. Additionally, we explored ongoing research initiatives and potential future applications of AI-driven approaches to further improve breast cancer risk prediction, thereby facilitating more effective screening and personalized risk management strategies. Objective and methods: This study presents a comprehensive overview of imaging and non-imaging features used in breast cancer risk prediction using traditional and AI models. The features reviewed in this study included imaging, radiomics, genomics, and clinical features. Furthermore, this survey systematically presented DL methods developed for breast cancer risk prediction, aiming to be useful for both beginners and advanced-level researchers. Results: A total of 600 articles were identified, 20 of which met the set criteria and were selected. Parallel benchmarking of DL models, along with natural language processing (NLP) applied to imaging and non-imaging features, could allow clinicians and researchers to gain greater awareness as they consider the clinical deployment or development of new models. This review provides a comprehensive guide for understanding the current status of breast cancer risk assessment using AI. Conclusion: This study offers investigators a different perspective on the use of AI for breast cancer risk prediction, incorporating numerous imaging and non-imaging features.

Cancer Pathways Targeted by Berberine: Role of microRNAs.

Cancer is a complex and heterogeneous malignant disease. Due to its multifactorial nature, including progressive changes in genetic, epigenetic, transcript, and protein levels, conventional therapeutics fail to save cancer patients. Evidence indicates that dysregulation of microRNA (miRNA) expression plays a crucial role in tumorigenesis, metastasis, cell proliferation, differentiation, metabolism, and signaling pathways. Moreover, miRNAs can be used as diagnostic and prognostic markers and therapeutic targets in cancer. Berberine, a naturally occurring plant alkaloid, has a wide spectrum of biological activities in different types of cancers. Inhibition of cell proliferation, metastasis, migration, invasion, and angiogenesis, as well as induction of cell cycle arrest and apoptosis in cancer cells, is reported by berberine. Recent studies suggested that berberine regulates many oncogenic and tumor suppressor miRNAs implicated in different phases of cancer. This review discussed how berberine inhibits cancer growth and propagation and regulates miRNAs in cancer cells. And how berberine-mediated miRNA regulation changes the landscape of transcripts and proteins that promote or suppress cancer progression. Overall, the underlying molecular pathways altered by berberine and miRNA influencing the tumor pathophysiology will enhance our understanding to combat the malignancy.

Deep learning, radiomics and radiogenomics applications in the digital breast tomosynthesis: a systematic review.

BACKGROUND: Recent advancements in computing power and state-of-the-art algorithms have helped in more accessible and accurate diagnosis of numerous diseases. In addition, the development of de novo areas in imaging science, such as radiomics and radiogenomics, have been adding more to personalize healthcare to stratify patients better. These techniques associate imaging phenotypes with the related disease genes. Various imaging modalities have been used for years to diagnose breast cancer. Nonetheless, digital breast tomosynthesis (DBT), a state-of-the-art technique, has produced promising results comparatively. DBT, a 3D mammography, is replacing conventional 2D mammography rapidly. This technological advancement is key to AI algorithms for accurately interpreting medical images. OBJECTIVE AND METHODS: This paper presents a comprehensive review of deep learning (DL), radiomics and radiogenomics in breast image analysis. This review focuses on DBT, its extracted synthetic mammography (SM), and full-field digital mammography (FFDM). Furthermore, this survey provides systematic knowledge about DL, radiomics, and radiogenomics for beginners and advanced-level researchers. RESULTS: A total of 500 articles were identified, with 30 studies included as the set criteria. Parallel benchmarking of radiomics, radiogenomics, and DL models applied to the DBT images could allow clinicians and researchers alike to have greater awareness as they consider clinical deployment or development of new models. This review provides a comprehensive guide to understanding the current state of early breast cancer detection using DBT images. CONCLUSION: Using this survey, investigators with various backgrounds can easily seek interdisciplinary science and new DL, radiomics, and radiogenomics directions towards DBT.

Invasive Breast Cancer: miR-24-2 Targets Genes Associated with Survival and Sensitizes MDA-MB-231 Cells to Berberine.

MicroRNA aberrations including that of miR-24-2 have been reported in various cancers. However, the target genes for miR-24-2 are yet to be identified and validated in invasive breast cancer and the triple-negative breast cancer (TNBC). Using in silico approaches and gene expression analyses, we identified and validated the target genes of miR-24-2 in invasive breast cancer, majority of which were TNBC. We studied the translational potential of these target genes using berberine in a TNBC cell line. Differentially expressed genes targeted by miR-24-2 were identified and analyzed for their survival effects using the The Cancer Genome Atlas-Breast Invasive Carcinoma (-BRCA) samples. Furthermore, we carried out protein-protein interaction, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene expression, and Kaplan-Meier survival analyses using common targets of miR-24-2 in invasive breast cancer/TNBC. We identified 11 biomarker candidate genes as crucial targets of miR-24-2. The survival of breast cancer patients was significantly associated with the low expressions of nine genes, including RACGAP1, KIAA1199, TIMM17A, LYRM7, IL1R1, SLC1A3, DTX4, L1CAM, and SAP30-like (SAP30L), and high expressions of two genes, SOD2 and HLA-DQB2. These in silico findings were validated by overexpressing miR-24-2 and assessing the expression pattern of these target genes in the TNBC MDA-MB-231 cells. miR-24-2 overexpression inhibited (by 20%; p < 0.001) cell proliferation and sensitized the anticancer effect of berberine. In all, this study reports on the novel target genes of miR-24-2 in invasive breast cancer/TNBC, and that miR-24-2 sensitizes MDA-MB-231 cells to berberine. These data lend evidence for the translational potentials of miR-24-2 for invasive breast cancer diagnostic and therapeutic innovation.

A Polyherbal Formulation Habb-e-Ustukhuddus Induces Apoptosis and Inhibits Cell Migration in Lung and Breast Cancer Cells without Any Toxicity in Mice.

OBJECTIVE: A polyherbal medicine, Habb-e-Ustukhuddus (HU), is used for its anti-inflammatory properties. However, the anticancer and chemopreventive properties of HU were not known, and Therefore, investigated in  the  present study. METHODS: Cancer cells were treated with 50-400 µg/ml HU and MTT, trypan blue, and clonogenic assays were performed. Propidium iodide (PI) staining, annexin V-FITC assay, and JC-1 staining were done for cell cycle progression, apoptosis, and mitochondrial membrane potential, respectively, using flow cytometry. Immunoblotting, cell migration and invasion assays were performed. Chemical characterization of HU was done through GC-MS and HPLC analyses. C57BL/6 mice were used to assess the in vivo toxicity of HU. RESULTS: While evaluating the anticancer activity, the methanolic extract of HU (50-400 µg/ml) strongly inhibited the growth and survival (P<0.05-0.001) of lung and breast cancer cells and increased the cell population in the sub-G1 phase of the cell cycle. HU caused apoptotic death of cancer cells (P<0.05-0.001), which was associated with the depolarization of mitochondrial membrane potential (Δψ) (P<0.001) and an increase in Bax to Bcl-2 protein ratio. Further, HU inhibited the invasion and migration of cancer cells, which was accompanied by an increase in the epithelial marker, E-cadherin, and a decrease in the mesenchymal marker, vimentin. The HU characterization by GC-MS and HPLC analyses showed the abundance of bioactive compounds including flavonoids and alkaloids. In the chemopreventive study, the oral administration of methanolic extract of the formulation HU (50 and 100 mg/kg body weight) to mice did not cause any toxicity and significantly increased the specific activities of hepatic drug metabolizing phase I and phase II enzymes, which suggested for its detoxification potential of xenobiotic compounds. CONCLUSION: Together, these results demonstrated the anticancer potential HU, without any apparent toxicity in mice, and thus HU could be further explored for its clinical utility in cancer control.

A Survey of Saudi General Practitioners on the Use of Thromboprophylaxis Guidelines and Risk Assessment Tools in Atrial Fibrillation.

Clinical practice guidelines advise patients with atrial fibrillation who are at risk for stroke to undergo thromboprophylaxis with oral anticoagulants. However, it is noted that guidelines are not always followed. We sought to learn how Saudi Arabian general practitioners (GPs) self-reported using risk assessment tools and atrial fibrillation clinical practice guidelines created by cardiology associations, as well as how GPs felt about the resources that were available. Through the use of a self-administered questionnaire, we carried out a cross-sectional survey. A total of two-hundred GPs participated in the study. The guidelines were frequently used when a clinical decision regarding anticoagulation therapy appeared difficult (n = 57, 28.4%). The most predominant strengths of participants' chosen clinical guidelines were clear recommendations (n = 56, 27.9%), easy-to-follow algorithms (n = 39, 16.9%), detailed recommendations supported by evidence (n = 34, 16.9%), and online availability (n = 27, 13.4%). Many respondents said they used a formal stroke risk assessment tool in addition to their clinical judgment as a GP for most decisions (60%). Most respondents preferred using the CHA2DS2-VASc (n = 106, 52.7%), CHA2DS2-VA (n = 45, 22.4%), CHADS2 (n = 35, 17.4%), and GARFIELD (n = 14, 7.0%). HAS-BLED (n = 100, 49.8%) and HEMORR2HAGES (n = 50, 24.9%) were the most frequently utilized formal tools for assessing the risk of bleeding among GPs. Over half of the participants referred to guidelines when deciding thromboprophylaxis in patients with atrial fibrillation. Additionally, many respondents used formal procedures for assessing the risks of bleeding and stroke in addition to their clinical judgement in their roles as GPs. The guideline was assessed as being extremely helpful overall by GPs who used it to make thromboprophylaxis decisions.

Neurobiology of depression in Parkinson's disease: Insights into epidemiology, molecular mechanisms and treatment strategies.

Parkinson's disease (PD) is characterized mainly by motor dysfunctions due to the progressive loss of dopaminergic neurons. However, PD patients experience a multitude of debilitating non-motor symptoms, including depression, which may have deleteriously detrimental effects on life. Depression is multifactorial and exhibits a bimodal progression in PD, but its underlying molecular mechanisms are poorly understood. Studies demonstrating the pathophysiology of depression in PD and the specific treatment strategies for depression-like symptoms in PD patients are largely lacking, often underrated, under-recognized and, consequently, inadequately/under-treated. Nevertheless, reports suggest that the incidence of depression is approximately 20-30% of PD patients and may precede the onset of motor symptoms. Diagnosing depression in PD becomes difficult due to the clinical overlap in symptomatology between the two diseases, and the nigrostriatal dysfunction alone is insufficient to explain depressive symptoms in PD. Therefore, the current study provides an overview of the molecular mechanisms underlying the development of depression in PD and new insights into developing current antidepressant strategies to treat depression in PD. This review will identify and understand the molecular pathological mechanisms of depression in PD that will fundamentally help tailoring therapeutic interventions for depressive symptoms in PD.

Neural crest cells development and neuroblastoma progression: Role of Wnt signaling.

Neuroblastoma (NB) is one of the most common heterogeneous extracranial cancers in infancy that arises from neural crest (NC) cells of the sympathetic nervous system. The Wnt signaling pathway, both canonical and noncanonical pathway, is a highly conserved signaling pathway that regulates the development and differentiation of the NC cells during embryogenesis. Reports suggest that aberrant activation of Wnt ligands/receptors in Wnt signaling pathways promote progression and relapse of NB. Wnt signaling pathways regulate NC induction and migration in a similar manner; it regulates proliferation and metastasis of NB. Inhibiting the Wnt signaling pathway or its ligands/receptors induces apoptosis and abrogates proliferation and tumorigenicity in all major types of NB cells. Here, we comprehensively discuss the Wnt signaling pathway and its mechanisms in regulating the development of NC and NB pathogenesis. This review highlights the implications of aberrant Wnt signaling in the context of etiology, progression, and relapse of NB. We have also described emerging strategies for Wnt-based therapies against the progression of NB that will provide new insights into the development of Wnt-based therapeutic strategies for NB.

Federated Learning for Privacy Preservation in Smart Healthcare Systems: A Comprehensive Survey.

Recent advances in electronic devices and communication infrastructure have revolutionized the traditional healthcare system into a smart healthcare system by using internet of medical things (IoMT) devices. However, due to the centralized training approach of artificial intelligence (AI), mobile and wearable IoMT devices raise privacy issues concerning the information communicated between hospitals and end-users. The information conveyed by the IoMT devices is highly confidential and can be exposed to adversaries. In this regard, federated learning (FL), a distributive AI paradigm, has opened up new opportunities for privacy preservation in IoMT without accessing the confidential data of the participants. Further, FL provides privacy to end-users as only gradients are shared during training. For these specific properties of FL, in this paper, we present privacy-related issues in IoMT. Afterwards, we present the role of FL in IoMT networks for privacy preservation and introduce some advanced FL architectures by incorporating deep reinforcement learning (DRL), digital twin, and generative adversarial networks (GANs) for detecting privacy threats. Moreover, we present some practical opportunities for FL in IoMT. In the end, we conclude this survey by discussing open research issues and challenges while using FL in future smart healthcare systems.

A novel 4'-brominated derivative of fisetin induces cell cycle arrest and apoptosis and inhibits EGFR/ERK1/2/STAT3 pathways in non-small-cell lung cancer without any adverse effects in mice.

The therapeutic toxicity and resistance to currently available treatment options are major clinical challenges for the management of lung cancer. As a novel strategy, we synthesized analogues of a known flavonol, fisetin, which has shown anti-tumorigenic potential against cancer in cell culture with no adverse effects in animal models. We studied the synthetic analogues of fisetin for their anti-cancer potential against lung cancer cells, toxicity in mice and efficacy in a xenograft model. Brominated fisetin analogues were screened for their effects on the viability of A549 and H1299 lung cancer cells, and three analogues (3a, 3b, 3c), showed improved activity compared to fisetin. These analogues were more effective in restricting lung cancer cell proliferation, inducing G2 M phase cell cycle arrest and apoptosis. The fisetin analogues also downregulated EGFR/ERK1/2/STAT3 pathways. Fisetin analogue-induced apoptosis was accompanied by a higher Bax to Bcl-2 expression ratio. Based on the in vitro studies, the most effective fisetin analogue 3b was evaluated for in vivo toxicity, wherein it did not show any hepatotoxicity or adverse health effects in mice. Furthermore, analogue 3b showed greater antitumor efficacy (p < .001) as compared to its parent compound fisetin in a human lung cancer cell xenograft study in athymic mice. Together, our data suggest that the novel fisetin analogue 3b is more effective in restricting lung cancer cell growth, both in vitro as well as in vivo, without any apparent toxicity, supporting its further development as a novel anti-lung cancer agent.

Naringenin alleviates paraquat-induced dopaminergic neuronal loss in SH-SY5Y cells and a rat model of Parkinson's disease.

Parkinson's disease (PD), a common neurodegenerative disease is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. The cause of dopaminergic loss in PD remains unknown for a long time, however, recent reports suggest oxidative stress plays a key role in the pathogenesis of PD. Paraquat (PQ), a widely used herbicide is an oxidative stress inducer that has been implicated as a potential risk factor for the development of PD. Flavonoids are naturally occurring polyphenolic compounds that display a variety of therapeutic properties against oxidative stress. Naringenin (NAR), a natural flavonoid, exhibits neuroprotection against PD-related pathology. However, studies on its neuroprotective role and the underlying mechanisms are scarce, therefore the present study explored the potential neuroprotective role of NAR in PQ-induced parkinsonism in SH-SY5Y cells and rat model. The effect of NAR on PQ-induced cellular toxicity was determined by measuring cell viability, oxidative stress, ATP levels and the same effect was determined by assessing behavioral, biochemical, immunohistochemical, qRT-PCR and Western blot in rat model. NAR treatment in SH-SY5Y cells resulted in increased cell viability, reduced oxidative stress, elevated mitochondrial membrane potential, and higher cellular ATP levels. In rats, NAR treatment resulted in significant neuroprotection against PQ-induced behavioral deficits, oxidative stress, mitochondrial dysfunction, and astrocytosis. NAR treatment significantly modulated PQ-induced mRNA expressions of DRD2, DAT, LRRK2, SNCA, ß-catenin, caspase-3, BDNF genes. NAR treatment increased TH protein expression and modulated its immunoreactivity in rat striatum. Also, GFAP decreased in response to NAR treatment. So, in the present study, NAR exhibits neuroprotection against PQ-induced neurotoxicity and neurodegeneration indicating its novel therapeutic potential against PD.

A modified truncated distribution for modeling the heavy tail, engineering and environmental sciences data.

Truncated models are imperative to efficiently analyze the finite data that we observe in almost all the real life situations. In this paper, a new truncated distribution having four parameters named Weibull-Truncated Exponential Distribution (W-TEXPD) is developed. The proposed model can be used as an alternative to the Exponential, standard Weibull and shifted Gamma-Weibull and three parameter Weibull distributions. The statistical characteristics including cumulative distribution function, hazard function, cumulative hazard function, central moments, skewness, kurtosis, percentile and entropy of the proposed model are derived. The maximum likelihood estimation method is employed to evaluate the unknown parameters of the W-TEXPD. A simulation study is also carried out to assess the performance of the model parameters. The proposed probability distribution is fitted on five data sets from different fields to demonstrate its vast application. A comparison of the proposed model with some extant models is given to justify the performance of the W-TEXPD.

Clinico-epidemiological Characteristics of Corrosive Ingestion: A Cross-sectional Study at a Tertiary Care Hospital of Multan, South-Punjab Pakistan.

Introduction Corrosive ingestion is a grave public health problem. It is a medical emergency and shows diverse clinical presentations. The ingestion of corrosive substances has devastating effects on upper gastrointestinal and respiratory tracts and the corrosive injury is associated with numerous life-threatening complications. The present study aims to explore the clinico-epidemiological characteristics of patients of corrosive ingestion presenting at a tertiary care hospital of Multan, Pakistan. Method The target study population consists of all the patients with primary diagnosis of corrosive ingestion who presented to the department of thoracic surgery, Nishtar Medical University Hospital Multan, Pakistan, from January 2016 to December 2017. The follow-up cases and the cases with ingestion of substances other than corrosives were not included in the study. All the included cases were evaluated by detailed history, thorough physical examination and the necessary investigations. The post-cor-rosive tissue damage was classified accord-ing to Zargar's classification system. All the demographic data and other variables were measured and recorded using a Performa. The data were analyzed by using computer program SPSS 21 version. Results The total study population was 206 patients. There were 135 females (65.5%) and 71 male patients (34.5%). Age ranged from 2 to 42 years (mean 23.44 ± 7.19). Only seven cases were found in the age group of 2-7 years. The residents of rural areas showed a slightly increased inclination towards corrosive ingestion. One hundred and ten cases were unmarried (53.4%) while 90 patients were married (43.7%). The incidence of corrosive ingestion was much high in illiterate/less educated patients belonging to the groups of lower socio-economic status. One hundred and ninety-seven patients ingested corrosive substances deliberately with the suicidal intention (95.6%). The acid used as bathroom cleaner and the laundry bleaches were the most commonly used corrosive agents. In 166 cases the corrosive materials were already present at home for domestic purposes (80.6%), but 18 subjects particularly purchased these corrosive substances to commit suicide. The quantity of ingested material ranged between 10 ml and 150 ml with a mean of 42.6 ml ± 33.2. The shortest hospital stay was one day, and the longest one was 60 days. Esophagus and oropharyngeal area were the most common site which sustained the corrosive injury, whereas corrosive injury to duodenum was least frequent (34.5 %). Conclusion Corrosive ingestion is a serious medical problem and it requires a multidisciplinary approach and a good coordination between different medical specialists. Underprivileged teenager females of rural areas are more likely to ingest corrosive materials with suicidal intention. In most of the ingestions, household cleaning products are used. Only the patients with severe corrosive injury should be admitted to intensive care units. Enforcing regulations for the manufacturers of household cleaning products can significantly reduce the incidence of this potentially fatal condition.

Acute middle East respiratory syndrome coronavirus infection in livestock Dromedaries, Dubai, 2014.

Camels carry Middle East respiratory syndrome coronavirus, but little is known about infection age or prevalence. We studied >800 dromedaries of all ages and 15 mother-calf pairs. This syndrome constitutes an acute, epidemic, and time-limited infection in camels <4 years of age, particularly calves. Delayed social separation of calves might reduce human infection risk.

Constraints to healthcare waste treatment in low-income countries - a case study from Somaliland.

In low-income countries, healthcare waste is mixed with the municipal waste stream and rarely receives special attention. This paper presents the lessons learned from a pilot project targeted to improve healthcare waste management in Hargeisa (Somaliland). The interventions were carried out in three of the main hospitals in the city. Consideration was also given to improve the overall situation regarding the management of healthcare waste. Three De Montfort incinerators were built and training was provided to operators, waste workers and healthcare personnel. Although the incinerators were constructed in accordance with the required standards, major constraints were identified in the operational phase: irregular de-ashing procedures, misuse of safety equipment, and ineffective separation of healthcare waste were seen in this phase. The paper concludes that in other small hospitals in the developing world, such as those in Hargeisa, on-site incineration by use of low-cost, small-scale incinerators could be successfully applied as an interim solution, provided that an agreed and acceptable plan of operation and maintenance is in place and responsibilities for the management of the facility are clearly identified. Moreover, when replicating this experience in other settings even greater importance should be given to the technical capacity building of operators and pressure should be exercised on local administrations in order to control and supervise the whole management system.

Invited manuscript poster on renal-related education American Society of Nephrology, Nov. 16-21, 2010. Do medical trainees receive adequate training in the management of acute kidney injury?

There has been increased interest in acute kidney injury (AKI) over the past decade following the recognition of the association of relatively small rises in serum creatinine with worse patient outcomes. This association has resulted in newly proposed definitions in AKI based on changes in serum creatinine. In 2009, the National Confidential Enquiry into Patient Outcomes and Death Adding Insult to Injury AKI study reported that only 50% of patients who died with a diagnosis of AKI received good care. The study identified multiple deficiencies and made a number of recommendations which included improving the training of undergraduate and postgraduate trainees in the management of AKI. The aim of the evaluation was to try and identify the perception of medical trainees in Leeds Teaching Hospitals of the training they had received on AKI. A simple questionnaire was used and captured the views of 73 trainees (including 13 final-year medical students). The evaluation indicated that the majority of trainees were unaware of newly proposed definitions of AKI, and many trainees felt that the training they had received in AKI was inadequate for their needs. Following this evaluation, we have made a number of changes to the training that is delivered to both undergraduate and postgraduate trainees in Leeds on the management of AKI.

Sampling household waste at source: lessons learnt in Gaborone.

Municipal solid waste (MSW) quantity and composition analysis is fundamental for the planning of municipal waste management services. The purpose of this paper is to report the results and experiences of sampling household waste at the source of generation in Gaborone, Botswana. The average generation rate, in kg capita(-1) day(-1), and percentages of various components of waste in Gaborone were determined using a statistically designed household sampling survey. The survey covered 47 households with different socio-economic characteristics over 21 days with 893 samples obtained. The results showed that the average waste generation rate for Gaborone was 0.33 kg capita(-1) day(-1). Contrary to common belief, the waste generation rate measured as in weight units was found not be directly related to household income. However, the packaging fractions of plastic and paper measured as volume had a direct relationship with household income. Across all income groups, the putrescible waste fraction constituted the highest proportion of the waste stream at approximately 68%. The main general conclusion is on the importance of practical considerations. As much as statistically designed sampling procedures provide a useful means of estimating the quantity and composition of household waste at source of generation, there are some practical issues that should be carefully considered during sampling to improve the accuracy and relevance of the results.