Forest yield prediction under different climate change scenarios using data intelligent models in Pakistan

Abstract This study aimed to develop and evaluate data driven models for prediction of forest yield under different climate change scenarios in the Gallies forest division of district Abbottabad, Pakistan. The Random Forest (RF) and Kernel Ridge Regression (KRR) models were developed and evaluated using yield data of two species (Blue pine and Silver fir) as an objective variable and climate data (temperature, humidity, rainfall and wind speed) as predictive variables. Prediction accuracy of both the models were assessed by means of root mean squared error (RMSE), mean absolute error (MAE), correlation coefficient (r), relative root mean squared error (RRMSE), Legates-McCabes (LM), Willmotts index (WI) and Nash-Sutcliffe (NSE) metrics. Overall, the RF model outperformed the KRR model due to its higher accuracy in forecasting of forest yield. The study strongly recommends that RF model should be applied in other regions of the country for prediction of forest growth and yield, which may help in the management and future planning of forest productivity in Pakistan.

Resumo Este estudo teve como objetivo desenvolver e avaliar modelos baseados em dados para previsão da produção florestal em diferentes cenários de mudanças climáticas na divisão florestal Gallies do distrito de Abbottabad, Paquistão. Os modelos Random Forest (RF) e Kernel Ridge Regression (KRR) foram desenvolvidos e avaliados usando dados de produção de duas espécies (pinheiro-azul e abeto-prateado) como uma variável objetiva e dados climáticos (temperatura, umidade, precipitação e velocidade do vento) como preditivos variáveis. A precisão da previsão de ambos os modelos foi avaliada por meio de erro quadrático médio (RMSE), erro absoluto médio (MAE), coeficiente de correlação (r), erro quadrático médio relativo (RRMSE), Legates-McCabes (LM), índice de Willmott (WI) e métricas Nash-Sutcliffe (NSE). No geral, o modelo RF superou o modelo KRR devido à sua maior precisão na previsão do rendimento florestal. O estudo recomenda fortemente que o modelo RF seja aplicado em outras regiões do país para previsão do crescimento e produtividade florestal, o que pode ajudar no manejo e planejamento futuro da produtividade florestal no Paquistão.

Environmental sustainability assessment of wooden furniture produced in Pakistan

Abstract Life cycle assessment was carried out for a conventional wooden furniture set produced in Mardan division of the Khyber Pakhtunkhwa province of Pakistan during 2018-19. Primary data regarding inputs and outputs were collected through questionnaire surveys from 100 conventional wooden furniture set manufacturers, 50 in district Mardan and 50 in district Swabi. In the present study, cradle-to-gate life cycle assessment approach was applied for a functional unit of one conventional wooden furniture set. Production weighted average data were modelled in the environmental impacts modelling software i.e., SimaPro v.8.5. The results showed that textile used in sofa set, wood preservative for polishing and preventing insects attack and petrol used in generator had the highest contribution to all the environmental impact categories evaluated. Total cumulative energy demand for wooden furniture set manufactured was 30,005 MJ with most of the energy acquired from non-renewable fossil fuel resources.

Resumo A abordagem de avaliação do ciclo de vida foi realizada para um conjunto de móveis de madeira convencional produzido na divisão Mardan da província de Khyber Pakhtunkhwa do Paquistão durante 2018-19. Os dados primários sobre entradas e saídas foram coletados por meio de pesquisas por questionário de 100 fabricantes de conjuntos de móveis de madeira convencionais, 50 no distrito de Mardan e 50 no distrito de Swabi. No presente estudo, a abordagem de avaliação do ciclo de vida do berço ao portão foi aplicada para uma unidade funcional de um conjunto de móveis de madeira convencional. Os dados da média ponderada da produção foram modelados no software de modelagem de impactos ambientais, isto é, SimaPro v.8.5. Os resultados mostraram que os têxteis usados no conjunto de sofás, o preservativo de madeira para polir e prevenir o ataque de insetos e a gasolina usada no gerador tiveram a maior contribuição em todas as categorias de impacto ambiental avaliadas. A demanda total acumulada de energia para o conjunto de móveis de madeira fabricado foi de 30.005 MJ, com a maior parte da energia adquirida de recursos de combustíveis fósseis não renováveis.

Environmental sustainability assessment of wooden furniture produced in Pakistan / Avaliação da sustentabilidade ambiental de móveis de madeira produzidos no Paquistão

Abstract Life cycle assessment was carried out for a conventional wooden furniture set produced in Mardan division of the Khyber Pakhtunkhwa province of Pakistan during 2018-19. Primary data regarding inputs and outputs were collected through questionnaire surveys from 100 conventional wooden furniture set manufacturers, 50 in district Mardan and 50 in district Swabi. In the present study, cradle-to-gate life cycle assessment approach was applied for a functional unit of one conventional wooden furniture set. Production weighted average data were modelled in the environmental impacts modelling software i.e., SimaPro v.8.5. The results showed that textile used in sofa set, wood preservative for polishing and preventing insects attack and petrol used in generator had the highest contribution to all the environmental impact categories evaluated. Total cumulative energy demand for wooden furniture set manufactured was 30,005 MJ with most of the energy acquired from non-renewable fossil fuel resources.

Resumo A abordagem de avaliação do ciclo de vida foi realizada para um conjunto de móveis de madeira convencional produzido na divisão Mardan da província de Khyber Pakhtunkhwa do Paquistão durante 2018-19. Os dados primários sobre entradas e saídas foram coletados por meio de pesquisas por questionário de 100 fabricantes de conjuntos de móveis de madeira convencionais, 50 no distrito de Mardan e 50 no distrito de Swabi. No presente estudo, a abordagem de avaliação do ciclo de vida do berço ao portão foi aplicada para uma unidade funcional de um conjunto de móveis de madeira convencional. Os dados da média ponderada da produção foram modelados no software de modelagem de impactos ambientais, isto é, SimaPro v.8.5. Os resultados mostraram que os têxteis usados ​​no conjunto de sofás, o preservativo de madeira para polir e prevenir o ataque de insetos e a gasolina usada no gerador tiveram a maior contribuição em todas as categorias de impacto ambiental avaliadas. A demanda total acumulada de energia para o conjunto de móveis de madeira fabricado foi de 30.005 MJ, com a maior parte da energia adquirida de recursos de combustíveis fósseis não renováveis.

Forest yield prediction under different climate change scenarios using data intelligent models in Pakistan / Previsão de produção florestal em diferentes cenários de mudanças climáticas usando modelos inteligentes de dados no Paquistão

Abstract This study aimed to develop and evaluate data driven models for prediction of forest yield under different climate change scenarios in the Gallies forest division of district Abbottabad, Pakistan. The Random Forest (RF) and Kernel Ridge Regression (KRR) models were developed and evaluated using yield data of two species (Blue pine and Silver fir) as an objective variable and climate data (temperature, humidity, rainfall and wind speed) as predictive variables. Prediction accuracy of both the models were assessed by means of root mean squared error (RMSE), mean absolute error (MAE), correlation coefficient (r), relative root mean squared error (RRMSE), Legates-McCabe's (LM), Willmott's index (WI) and Nash-Sutcliffe (NSE) metrics. Overall, the RF model outperformed the KRR model due to its higher accuracy in forecasting of forest yield. The study strongly recommends that RF model should be applied in other regions of the country for prediction of forest growth and yield, which may help in the management and future planning of forest productivity in Pakistan.

Resumo Este estudo teve como objetivo desenvolver e avaliar modelos baseados em dados para previsão da produção florestal em diferentes cenários de mudanças climáticas na divisão florestal Gallies do distrito de Abbottabad, Paquistão. Os modelos Random Forest (RF) e Kernel Ridge Regression (KRR) foram desenvolvidos e avaliados usando dados de produção de duas espécies (pinheiro-azul e abeto-prateado) como uma variável objetiva e dados climáticos (temperatura, umidade, precipitação e velocidade do vento) como preditivos variáveis. A precisão da previsão de ambos os modelos foi avaliada por meio de erro quadrático médio (RMSE), erro absoluto médio (MAE), coeficiente de correlação (r), erro quadrático médio relativo (RRMSE), Legates-McCabe's (LM), índice de Willmott (WI) e métricas Nash-Sutcliffe (NSE). No geral, o modelo RF superou o modelo KRR devido à sua maior precisão na previsão do rendimento florestal. O estudo recomenda fortemente que o modelo RF seja aplicado em outras regiões do país para previsão do crescimento e produtividade florestal, o que pode ajudar no manejo e planejamento futuro da produtividade florestal no Paquistão.

Enterotoxigenic methicillin resistant Staphylococcus aureus contamination in salted fish from Gwadar Balochistan / Contaminação de Staphylococcus aureus resistente à meticilina enterotoxigênica em peixes salgados de Gwadar Balochistan

Staphylococcus aureus is an important foodborne pathogen associated to food intoxication and other multiple infections in human being. Its presence in salted food is a serious issue due to its salt tolerance potential. A study was conducted to analyze the presence of enterotoxins producing drug resistance S. aureus in salted sea fish from Gwadar. Freshly persevered samples (n=50) of salted fish were subjected to analyze the presence of S. aureus using 16S rRNA and Nuc genes primers. The isolates were then evaluated for drug resistance and enterotoxins producing potential using specific primers for MecA (methicillin resistance gene), (SEA) staphylococcal enterotoxin A and (SEB) staphylococcal enterotoxin B genes. Total 13/50 (26%) of the samples were found positive for the presence of S. aureus, preliminary confirmed with biochemical profiling and finally with the help of target genes presence. The isolates were found showing 100% resistant to methicillin, which were molecularly confirmed by the presence of MecA gene present in genome. The isolates 5/13 (38%) were positive for SEA and 3/13 (23%) for SEB genes, whereas 2/13 (15%) were confirmed having both SEA and SEB genes in its genome. It was also confirmed that all the isolates were capable to form biofilm over the glass surfaces. It was concluded that the study confirmed the presence of enterotoxigenic methicillin resistance Staphylococcus aurous (MRSA) in salted fish product, that poses gross food safety concern. Preventive and control measures are necessary to handle this serious food safety concern.

Staphylococcus aureus é um importante patógeno de origem alimentar associado à intoxicação alimentar e outras infecções múltiplas em seres humanos. Sua presença em alimentos salgados é um problema sério devido ao seu potencial de tolerância ao sal. Um estudo foi realizado para analisar a presença de enterotoxinas produtoras de resistência a drogas S. aureus em peixes salgados do mar de Gwadar. Amostras recém-perseveradas (n = 50) de peixes salgados foram submetidas à análise da presença de S. aureus usando os primers dos genes 16S rRNA e Nuc. Os isolados foram então avaliados quanto à resistência a drogas e potencial de produção de enterotoxinas usando primers específicos para os genes MecA (gene de resistência à meticilina), (SEA) enterotoxina A estafilocócica e (SEB) enterotoxina B estafilocócica genes. Um total de 13/50 (26%) das amostras foi considerado positivas para a presença de S. aureus, confirmadas preliminarmente com perfis bioquímicos e finalmente com a ajuda da presença de genes-alvo. Os isolados foram encontrados com 100% de resistência à meticilina, os quais foram confirmados molecularmente pela presença do gene MecA no genoma. Os isolados 5/13 (38%) foram positivos para SEA e 3/13 (23%) para genes SEB, enquanto 2/13 (15%) foram confirmados tendo os genes SEA e SEB em seu genoma. Também foi verificado que todos os isolados foram capazes de formar biofilme sobre as superfícies de vidro. Concluiu-se que o estudo confirmou a presença de Staphylococcus aurous resistente à meticilina enterotoxigênica (MRSA) em produtos de peixe salgado, o que representa uma grande preocupação para a segurança alimentar. Medidas preventivas e de controle são necessárias para lidar com essa grave preocupação com a segurança alimentar.

Enterotoxigenic methicillin resistant Staphylococcus aureus contamination in salted fish from Gwadar Balochistan

Abstract Staphylococcus aureus is an important foodborne pathogen associated to food intoxication and other multiple infections in human being. Its presence in salted food is a serious issue due to its salt tolerance potential. A study was conducted to analyze the presence of enterotoxins producing drug resistance S. aureus in salted sea fish from Gwadar. Freshly persevered samples (n=50) of salted fish were subjected to analyze the presence of S. aureus using 16S rRNA and Nuc genes primers. The isolates were then evaluated for drug resistance and enterotoxins producing potential using specific primers for MecA (methicillin resistance gene), (SEA) staphylococcal enterotoxin A and (SEB) staphylococcal enterotoxin B genes. Total 13/50 (26%) of the samples were found positive for the presence of S. aureus, preliminary confirmed with biochemical profiling and finally with the help of target genes presence. The isolates were found showing 100% resistant to methicillin, which were molecularly confirmed by the presence of MecA gene present in genome. The isolates 5/13 (38%) were positive for SEA and 3/13 (23%) for SEB genes, whereas 2/13 (15%) were confirmed having both SEA and SEB genes in its genome. It was also confirmed that all the isolates were capable to form biofilm over the glass surfaces. It was concluded that the study confirmed the presence of enterotoxigenic methicillin resistance Staphylococcus aurous (MRSA) in salted fish product, that poses gross food safety concern. Preventive and control measures are necessary to handle this serious food safety concern.

Resumo Staphylococcus aureus é um importante patógeno de origem alimentar associado à intoxicação alimentar e outras infecções múltiplas em seres humanos. Sua presença em alimentos salgados é um problema sério devido ao seu potencial de tolerância ao sal. Um estudo foi realizado para analisar a presença de enterotoxinas produtoras de resistência a drogas S. aureus em peixes salgados do mar de Gwadar. Amostras recém-perseveradas (n = 50) de peixes salgados foram submetidas à análise da presença de S. aureus usando os primers dos genes 16S rRNA e Nuc. Os isolados foram então avaliados quanto à resistência a drogas e potencial de produção de enterotoxinas usando primers específicos para os genes MecA (gene de resistência à meticilina), (SEA) enterotoxina A estafilocócica e (SEB) enterotoxina B estafilocócica genes. Um total de 13/50 (26%) das amostras foi considerado positivas para a presença de S. aureus, confirmadas preliminarmente com perfis bioquímicos e finalmente com a ajuda da presença de genes-alvo. Os isolados foram encontrados com 100% de resistência à meticilina, os quais foram confirmados molecularmente pela presença do gene MecA no genoma. Os isolados 5/13 (38%) foram positivos para SEA e 3/13 (23%) para genes SEB, enquanto 2/13 (15%) foram confirmados tendo os genes SEA e SEB em seu genoma. Também foi verificado que todos os isolados foram capazes de formar biofilme sobre as superfícies de vidro. Concluiu-se que o estudo confirmou a presença de Staphylococcus aurous resistente à meticilina enterotoxigênica (MRSA) em produtos de peixe salgado, o que representa uma grande preocupação para a segurança alimentar. Medidas preventivas e de controle são necessárias para lidar com essa grave preocupação com a segurança alimentar.

GCMS characterization and biological potential of the seeds and aerial part of Galium tricorne Stokes.

Natural products have long been proven very effective against various challenging diseases including cancer and bacterial infections. Galium tricorne is one of the important source of natural products, which has not been explored till date in spite of its profound ethnomedicinal prominence. The current study has been designed to explore the biological potential of G. tricorne and to extract and isolate chemical constituents from its aerial part and seeds respectively along with identification of their chemical constituents. Phytochemical screening was performed to figure out the presence of secondary metabolite in G. tricorne. Crude Methanolic extract (Gt.Crd), which was obtained from the aerial part while the fatty acids were extracted from the seeds, which were later on analyzed by GCMS. Similarly, Well Diffusion and MTT method were used for antibacterial activity and cancer cell line assay respectively. To evaluate the cytotoxic potential, brine shrimps were used. Likewise, in Gas Chromatography-Mass Spectroscopy (GC-MS) analysis a total number of 23 compounds were identified in Gt.Crd extract out of which 7 compounds were sorted out to have some sort of toxicity profile. In the same fashion, 5 fatty acids were identified in the seeds of G. tricorne. Moreover, among the fractions, chloroform fraction (Gt.Chf) exhibited greater zone of inhibition (ZOI) 20.37 mm followed by Gt.Crd 18.40 mm against S. aureus and S. pyogenes respectively. In cytotoxicity Gt.Chf was more active followed by ethyl acetate fraction (Gt.Eta) by exhibiting 88.32±0.62% (LC50=60 µg/mL) and 73.95±2.25% (LC50=80 µg/mL) respectively at 1000 µg/mL concentration of the tested sample. Gt.Chf exhibited greater cell line inhibitory activity (IC50=61 µg/mL) against HeLa cell line. Similarly, Gt.Crd displayed IC50 values of 167.84 µg/mL and 175.46 µg/mL against HeLa and NIH/3T3 cell line respectively. Based on the literature review and screenings, it may be concluded that the aerial part and seeds of G. tricorne are the rich sources of bioactive compounds. The results of the current study also authenticate the scientific background for the ethnomedicinal uses of G. tricorne.

A Multicentre Retrospective Study of Fulvestrant Use and Efficacy in Advanced/Metastatic Breast Cancer.

AIMS: Fulvestrant is a selective oestrogen receptor (ER) degrader used in postmenopausal women with hormone receptor-positive advanced breast cancer. The study aim was to analyse demographics and outcomes of UK patients treated with fulvestrant monotherapy at nine representative centres. MATERIALS AND METHODS: Medical records of 459 patients with locally advanced or metastatic ER-positive, HER2-negative breast cancer treated with fulvestrant between August 2011 and November 2018 at nine UK centres were reviewed. Data were collated on demographics, progression-free survival, overall survival and disease response at first radiological assessment following fulvestrant initiation. Patients still alive by December 2018 were censored. RESULTS: Data from 429 of the 459 patients identified were eligible for inclusion in the analysis. The median age was 69 (range 21-95) and 64% (n = 275) had Eastern Cooperative Oncology Group performance status 0-1. Bone was the most commonly involved metastatic site (72%, n = 306). However, 295 (69%) patients had visceral involvement. Patients had received a median 2 (range 0-5) prior lines of endocrine therapy and median 0 (range 0-6) prior chemotherapies. Fulvestrant was first-line therapy in 43 patients (10%). The median duration of treatment was 5 months (range 1-88). The median progression-free survival was 5.5 months. In 51% of 350 patients radiologically assessed, there was evidence of disease response to fulvestrant. Fifteen per cent of these had a complete/partial response. Fulvestrant was discontinued predominantly due to disease progression, with 3% discontinued solely due to adverse events. The median overall survival for the whole cohort was 22.5 months (range 0-88). CONCLUSIONS: This is one of the largest studied cohorts of breast cancer patients treated with fulvestrant. This heavily endocrine-pretreated population reflects real-life use in the UK. Within this context, our retrospective data show that patients can experience maintained disease response when treated with fulvestrant, supporting the importance of equitable availability for all UK patients.

Biomedical applications of nano-titania in theranostics and photodynamic therapy.

Titanium dioxide (TiO2) is one of the most abundantly used nanomaterials for human life. It is used in sunscreen, photovoltaic devices, biomedical applications and as a food additive and environmental scavenger. Nano-TiO2 in biomedical applications is well documented. It is used in endoprosthetic implants and early theranostics of neoplastic and non-neoplastic maladies as a photodynamic therapeutic agent and as vehicles in nano-drug delivery systems. Herein, we focus on the recent advancements and applications of nano-TiO2 in bio-nanotechnology, nanomedicine and photodynamic therapy (PDT).

The role of testicular nuclear receptor 4 in chemo-resistance of docetaxel in castration-resistant prostate cancer.

Docetaxel-based therapy is one of the first-line options for castration-resistant prostate cancer (CRPC). However, a large proportion of CRPC patients show different extents of docetaxel resistance. The current study aims to investigate the role of testicular nuclear receptor 4 (TR4) in docetaxel resistance in CRPC. TR4 expression level in prostate biopsy samples from CRPC patients treated with docetaxel was measured by immunohistochemistry (IHC). Alternation of TR4 expression in prostate cancer (PCa) cell line PC3 was applied to find out the influence of TR4 on half-maximal inhibitory concentration (IC50), cell viability and cell apoptosis. Patients who failed to achieve prostate-specific antigen (PSA) response (<50% PSA reduction from baseline) after docetaxel-based chemotherapy had a comparatively higher TR4 expression than those who achieved PSA response (⩾50% PSA reduction from baseline). Knocking down TR4 in PC3 cells led to a lower IC50 dose, poorer cell viability and more cell apoptosis when treated with docetaxel, whereas overexpression of TR4 in PC3 led to a higher IC50 dose, better cell viability and less cell apoptosis. TR4 enhances the chemo-resistance of docetaxel in CRPC. It may serve as a biomarker to determine the prognosis of docetaxel-based therapy and as a potential therapy target to combine with docetaxel to better suppress CRPC.

Metabolomic Analysis of Liver Tissue from the VX2 Rabbit Model of Secondary Liver Tumors.

Purpose. The incidence of liver neoplasms is rising in USA. The purpose of this study was to determine metabolic profiles of liver tissue during early cancer development. Methods. We used the rabbit VX2 model of liver tumors (LT) and a control group consisting of sham animals implanted with Gelfoam into their livers (LG). After two weeks from implantation, liver tissue from lobes with and without tumor was obtained from experimental animals (LT+/LT-) as well as liver tissue from controls (LG+/LG-). Peaks obtained by Gas Chromatography-Mass Spectrometry were subjected to identification. 56 metabolites were identified and their profiles compared between groups using principal component analysis (PCA) and a mixed-effect two-way ANOVA model. Results. Animals recovered from surgery uneventfully. Analyses identified a metabolite profile that significantly differs in experimental conditions after controlling the False Discovery Rate (FDR). 16 metabolites concentrations differed significantly when comparing samples from (LT+/LT-) to samples from (LG+/LG-) livers. A significant difference was also shown in 20 metabolites when comparing samples from (LT+) liver lobes to samples from (LT-) liver lobes. Conclusion. Normal liver tissue harboring malignancy had a distinct metabolic signature. The role of metabolic profiles on liver biopsies for the detection of early liver cancer remains to be determined.

The role of mast cells on angiogenesis in oral squamous cell carcinoma.

OBJECTIVE: Angiogenesis or neovascularization has long been known to aid in progression and metastasis of malignant tumors. Tumor angiogenesis is a complex event mediated by angiogenic factors released from cancer cells and or by host immune cells. Mast cells may induce tumor progression and potentiate metastasis by stimulating angiogenesis. The purpose of the present study was to validate topographic distribution of micro vessel density (MVD) and mast cell density (MCD) and help to elucidate the possible role of mast cells in tumor angiogenesis and correlating this with advanced disease parameters. . STUDY DESIGN: MVD and MCD were investigated in tumor specimens from 30 patients diagnosed with different histologic grades of oral squamous cell carcinoma (OSCC). Intratumor vessels were stained with collagen Type IV antibody and mast cells with Toluidine blue before being measured by light microscopy. RESULTS: There was a significant correlation between MVD and disease progression and number of blood vessels increased from well to poorly differentiated OSCC where as MCD decreased. CONCLUSIONS: These findings suggest that angiogenesis indeed occur in OSCC and might be used as an index to inflect the aggression of the disease however mast cells make up only a part of complex process of angiogenesis along with other factors secreted by tumor.

Lost in publication: Half of all renal practice evidence is published in non-renal journals.

Physicians often scan a select number of journals to keep up to date with practice evidence for patients with kidney conditions. This raises the question of where relevant studies are published. We performed a bibliometric analysis using 195 renal systematic reviews. Each review used a comprehensive method to identify all primary studies for a focused clinical question relevant to patient care. We compiled all the primary studies included in these reviews, and considered where each study was published. Of the 2779 studies, 1351 (49%) were published in the top 20 journals. Predictably, this list included Transplantation Proceedings (5.9% of studies), Kidney International (5.3%), American Journal of Kidney Diseases (4.7%), Nephrology Dialysis Transplantation (4.3%), Transplantation (4.2%), and Journal of the American Society of Nephrology (2.4%). Ten non-renal journals were also on this list, including New England Journal of Medicine (2.4%), Lancet (2.3%), and Diabetes Care (2.2%). The remaining 1428 (51%) studies were published across other 446 journals. When the disciplines of all journals were considered, 59 were classified as renal or transplant journals (42% of articles). Other specialties included general and internal medicine (16%), endocrinology (diabetes) and metabolism (6.5%), surgery (6.2%), cardiovascular diseases (6.1%), pediatrics (4.3%), and radiology (3.3%). About half of all renal practice evidence is published in non-renal journals. Browsing the top journals is important. However, relevant studies are also scattered across a large range of journals that may not be routinely scanned by busy physicians, and keeping up with this literature requires other continuing education strategies.

Fenretinide stimulates redox-sensitive ceramide production in breast cancer cells: potential role in drug-induced cytotoxicity.

The synthetic retinoid N-(4-hydroxphenyl) retinamide (4HPR) has manifold actions, which may contribute to its chemopreventive effects on breast cancer cell growth and progression. A role for ceramide as a stress-response signal is investigated here during the cytotoxic action of 4HPR in MCF-7 cells. N-(4-hydroxphenyl) retinamide induced a dose-dependent decline in cell growth and survival associated with a maximal 10-fold increase in ceramide production at 10 microM. N-(4-hydroxphenyl) retinamide exhibited a greater potency than all-trans retinoic acid (ATRA) on growth inhibition and ceramide production. The synthetic peroxisome proliferator-activated receptors agonist troglitazone (TGZ), but not the native ligand 15-deoxy-delta 12,14-prostaglandin J2, abrogated both these actions of 4HPR but not that of ATRA. The antioxidant N-acetylcysteine mimicked the abrogative effect of TGZ on 4HPR action, while the exogenous oxidant H2O2 also stimulated ceramide production. The inhibitors of de novo ceramide synthesis, fumonisin B1 and myriocin, blocked the ceramide response to 4HPR and partially reversed the apoptotic response, but did not prevent the overall decline in cell survival. The pancaspase inhibitor Z-VAD fmk reduced the decrease in cell survival caused by 4HPR, but did not affect the ceramide response. These findings describe a novel redox-sensitive elevation of ceramide levels associated with the cytotoxic response of breast cancer cells to 4HPR. However, a major mediatory role for this sphingolipid in this context remains equivocal.

Visceral leishmaniasis in District Dir, NWFP.

Visceral leishmaniasis is endemic in District Dir, NWFP. We evaluated 10 patients with visceral leishmaniasis at DHQ Hospital Timergara District Dir, N.W.F.P. All patients were in the age range 2 to 10 years. The predominant clinical features in these were chronic fever (10), splenomegaly (10), hepatomegaly (10), weight loss (10) and abdominal distention (5). Lymphadenopathy was absent. Common laboratory abnormalities included anaemia (10), leucopenia (7), thrombocytopenia (10) and hypergammaglobulinaemia (10). Formal Gel test was positive in all patients (100%) and all had positive bone marrow smears for Leishmania Donovani (L.D.) bodies (10). The response to stibogluconate (Glucantime Sodium) therapy was good with a 100 percent cure rate.

Leptomeningeal metastases: comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias.

We reviewed 63 cases of cytologically confirmed leptomeningeal metastases (LM). 31 (49%) had solid tumors 17 (27%) had leukemia and 15 (24%) had lymphoma. The most common presenting symptom was pain (76%) with radicular discomfort (58%), headache (32%), neck or back pain (17%). The predominant neurological signs were mental status abnormalities (49%), weakness (47%), seizures (14%). The mode of presentation varied with tumor type. Patients with leukemia (18%) and lymphoma (13%) tended to present frequently with LM without systemic involvement, or during periods of apparent remission (leukemia 35%, lymphoma 27%), while patients with solid tumors had established systemic metastases (90%) at time of presentation. Laboratory studies did not vary among the groups. 71% had positive cytology on the first lumbar puncture (LP) and only 8% required more than 2 LPs. The cell count was a poor predictor of positive cytology as 29% of LP's with positive cytology and 36% of all LP's had less than 4 cells/mm. We conclude that 1) LM presents with pain and seizures more frequently than has been previously recognized; 2) LM is frequently the mode of presentation in patients with leukemia and lymphoma and; 3) cytology is positive frequently in CSF specimens with normal cell counts and chemistries.