Efficient leukocytes detection and classification in microscopic blood images using convolutional neural network coupled with a dual attention network.

Leukocytes, also called White Blood Cells (WBCs) or leucocytes, are the cells that play a pivotal role in human health and are vital indicators of diseases such as malaria, leukemia, AIDS, and other viral infections. WBCs detection and classification in blood smears offers insights to pathologists, aiding diagnosis across medical conditions. Traditional techniques, including manual counting, detection, classification, and visual inspection of microscopic images by medical professionals, pose challenges due to their labor-intensive nature. However, traditional methods are time consuming and sometimes susceptible to errors. Here, we propose a high-performance convolutional neural network (CNN) coupled with a dual-attention network that efficiently detects and classifies WBCs in microscopic thick smear images. The main aim of this study was to enhance clinical hematology systems and expedite medical diagnostic processes. In the proposed technique, we utilized a deep convolutional generative adversarial network (DCGAN) to overcome the limitations imposed by limited training data and employed a dual attention mechanism to improve accuracy, efficiency, and generalization. The proposed technique achieved overall accuracy rates of 99.83%, 99.35%, and 99.60% for the peripheral blood cell (PBC), leukocyte images for segmentation and classification (LISC), and Raabin-WBC benchmark datasets, respectively. Our proposed approach outperforms state-of-the-art methods in terms of accuracy, highlighting the effectiveness of the strategies employed and their potential to enhance diagnostic capabilities and advance real-world healthcare practices and diagnostic systems.

Health behaviors and care seeking practices for childhood diarrhea and pneumonia in a rural district of Pakistan: A qualitative study.

Diarrhea and pneumonia are the leading causes of morbidity and mortality in children under five, and Pakistan is amongst the countries with the highest burden and low rates of related treatment coverage. We conducted a qualitative study as part of the formative phase to inform the design of the Community Mobilization and Community Incentivization (CoMIC) cluster randomized control trial (NCT03594279) in a rural district of Pakistan. We conducted in-dept interviews and focused group discussions with key stakeholders using a semi-structured study guide. Data underwent rigorous thematic analysis and major themes identified included socio-cultural dynamics, community mobilization and incentives, behavioral patterns and care seeking practices for childhood diarrhea and pneumonia, infant and young child feeding practices (IYCF), immunization, water sanitation and hygiene (WASH) and access to healthcare. This study highlights shortcomings in knowledge, health practices and health systems. There was to a certain extent awareness of the importance of hygiene, immunization, nutrition, and care-seeking, but the practices were poor due to various reasons. Poverty and lifestyle were considered prime factors for poor health behaviors, while health system inefficiencies added to these as rural facilities lack equipment and supplies, resources, and funding. The community identified that intensive inclusive community engagement and demand creation strategies tied to conditioned short term tangible incentives could help foster behavior change.

Effect of varying thickness properties of the slow release fertilizer films on morphology, biodegradability, urea release, soil health, and plant growth.

Green biomass is a renewable and biodegradable material that has the potential use to trap urea to develop a high-efficiency urea fertilizer for crops' better performance. Current work examined the morphology, chemical composition, biodegradability, urea release, soil health, and plant growth effects of the SRF films subjected to changes in the thickness of 0.27, 0.54, and 1.03 mm. The morphology was examined by Scanning Electron Microscopy, chemical composition was analyzed by Infrared Spectroscopy, and biodegradability was assessed through evolved CO2 and CH4 quantified through Gas Chromatography. The chloroform fumigation technique was used for microbial growth assessment in the soil. The soil pH and redox potential were also measured using a specific probe. CHNS analyzer was used to calculate the total carbon and total nitrogen of the soil. A plant growth experiment was conducted on the Wheat plant (Triticum sativum). The thinner the films, the more they supported the growth and penetration of the soil's microorganisms mainly the species of fungus possibly due to the presence of lignin in films. The fingerprint regions of the infrared spectrum of SRF films showed all films in soil changed in their chemical composition due to biodegradation but the increase in the thickness possibly provides resistance to the films' losses. The higher thickness of the film delayed the rate and time for biodegradation and the release of methane gas in the soil. The 1.03 mm film (47% in 56 days) and 0.54 mm film (35% in 91 days) showed the slowest biodegradability as compared to the 0.27 mm film with the highest losses (60% in 35 days). The slow urea release is more affected by the increase in thickness. The Korsymer Pappas model with release exponent value of < 0.5 explained the release from the SRF films followed the quasi-fickian diffusion and also reduced the diffusion coefficient for urea. An increase in the pH and decrease in the redox potential of the soil is correlated with higher total organic content and total nitrogen in the soil in response to amending SRF films with variable thickness. Growth of the wheat plant showed the highest average plant length, leaf area index and grain per plant in response to the increase in the film's thickness. This work developed an important knowledge to enhance the efficiency of film encapsulated urea that can better slow the urea release if the thickness is optimized.

Genome-wide investigation of ZINC-IRON PERMEASE (ZIP) genes in Areca catechu and potential roles of ZIPs in Fe and Zn uptake and transport.

Iron (Fe) and Zinc (Zn) are essential nutrient elements for plant growth and development. Here, we observed the effects of Fe and Zn deficiency in seedlings of Areca catechu L. (areca palm), one of the most cultured palm trees in tropic regions. Results revealed that Fe deficiency causes strong chlorosis with the significantly decreased chlorophyll biosynthesis level and photosynthetic activities in the top third young leaf (L3) of seedlings. Zn deficiency caused light chlorosis in all three young leaves which slightly decreased chlorophyll biosynthesis and photosynthetic activities. Analysis of the Fe and Zn concentration in leaves and roots indicated that absorption and distribution of these two ions share cooperative pathways, since Zn deficiency caused Fe increasing, and vice versa. Therefore, we focused on the ZINC-IRON PERMEASE (ZIP) genes in areca trees. From the whole-genome data set we obtained, 6 ZIP genes were classified, and a phylogenetic tree was constructed with other 38 ZIP genes from model plants to find their potential functions. We also analyzed the expression pattern of AcZIP1-6 genes under Zn and Fe deficiency by transcriptomic approaches. With these results, we constructed an expression atlas of AcZIP1-6 genes in leaves and roots of areca seedlings with the dynamic expression levels under Fe and Zn deficient conditions. In conclusion, we provide evidence to understand the absorption and transport of nutrient elements, Fe and Zn, in the tropic agricultural plant A. catechu.

Multi-Class Skin Lesion Detection and Classification via Teledermatology.

Teledermatology is one of the most illustrious applications of telemedicine and e-health. In this field, telecommunication technologies are utilized to transfer medical information to the experts. Due to the skin's visual nature, teledermatology is an effective tool for the diagnosis of skin lesions especially in rural areas. Furthermore, it can also be useful to limit gratuitous clinical referrals and triage dermatology cases. The objective of this research is to classify the skin lesion image samples, received from different servers. The proposed framework is comprised of two module, which include the skin lesion localization/segmentation and the classification. In the localization module, we propose a hybrid strategy that fuses the binary images generated from the designed 16-layered convolutional neural network model and an improved high dimension contrast transform (HDCT) based saliency segmentation. To utilize maximum information extracted from the binary images, a maximal mutual information method is proposed, which returns the segmented RGB lesion image. In the classification module, a pre-trained DenseNet201 model is re-trained on the segmented lesion images using transfer learning. Afterward, the extracted features from the two fully connected layers are down-sampled using the t-distribution stochastic neighbor embedding (t-SNE) method. These resultant features are finally fused using a multi canonical correlation (MCCA) approach and are passed to a multi-class ELM classifier. Four datasets (i.e., ISBI2016, ISIC2017, PH2, and ISBI2018) are employed for the evaluation of the segmentation task, while HAM10000, the most challenging dataset, is used for the classification task. The experimental results in comparison with the state-of-the-art methods affirm the strength of our proposed framework.

WEENet: An Intelligent System for Diagnosing COVID-19 and Lung Cancer in IoMT Environments.

The coronavirus disease 2019 (COVID-19) pandemic has caused a major outbreak around the world with severe impact on health, human lives, and economy globally. One of the crucial steps in fighting COVID-19 is the ability to detect infected patients at early stages and put them under special care. Detecting COVID-19 from radiography images using computational medical imaging method is one of the fastest ways to diagnose the patients. However, early detection with significant results is a major challenge, given the limited available medical imaging data and conflicting performance metrics. Therefore, this work aims to develop a novel deep learning-based computationally efficient medical imaging framework for effective modeling and early diagnosis of COVID-19 from chest x-ray and computed tomography images. The proposed work presents "WEENet" by exploiting efficient convolutional neural network to extract high-level features, followed by classification mechanisms for COVID-19 diagnosis in medical image data. The performance of our method is evaluated on three benchmark medical chest x-ray and computed tomography image datasets using eight evaluation metrics including a novel strategy of cross-corpse evaluation as well as robustness evaluation, and the results are surpassing state-of-the-art methods. The outcome of this work can assist the epidemiologists and healthcare authorities in analyzing the infected medical chest x-ray and computed tomography images, management of the COVID-19 pandemic, bridging the early diagnosis, and treatment gap for Internet of Medical Things environments.

Deep Learning for Multigrade Brain Tumor Classification in Smart Healthcare Systems: A Prospective Survey.

Brain tumor is one of the most dangerous cancers in people of all ages, and its grade recognition is a challenging problem for radiologists in health monitoring and automated diagnosis. Recently, numerous methods based on deep learning have been presented in the literature for brain tumor classification (BTC) in order to assist radiologists for a better diagnostic analysis. In this overview, we present an in-depth review of the surveys published so far and recent deep learning-based methods for BTC. Our survey covers the main steps of deep learning-based BTC methods, including preprocessing, features extraction, and classification, along with their achievements and limitations. We also investigate the state-of-the-art convolutional neural network models for BTC by performing extensive experiments using transfer learning with and without data augmentation. Furthermore, this overview describes available benchmark data sets used for the evaluation of BTC. Finally, this survey does not only look into the past literature on the topic but also steps on it to delve into the future of this area and enumerates some research directions that should be followed in the future, especially for personalized and smart healthcare.

The newly synthesized compounds (NCHDH and NTHDH) attenuates LPS-induced septicemia and multi-organ failure via Nrf2/HO1 and HSP/TRVP1 signaling in mice.

The sepsis is considered as serious clinic-pathological condition related with high rate of morbidity and mortality in critical care settings. In the proposed study, the hydrazides derivatives N-(benzylidene)-2-((2-hydroxynaphthalen-1-yl)diazenyl)benzohydrazides (1-2) (NCHDH and NTHDH) were investigated against the LPS-induced sepsis in rodents. The NCHDH and NTHDH markedly improved the physiological sign and symptoms associated with the sepsis such as mortality, temperature, and clinical scoring compared to negative control group, which received only LPS (i.p.). The NCHDH and NTHDH also inhibited the production of the NO and MPO compared to the negative control. Furthermore, the treatment control improved the histological changes markedly of all the vital organs. Additionally, the Masson's trichrome and PAS (Periodic Acid Schiff) staining also showed improvement in the NCHDH and NTHDH treated group in contrast to LPS-induced group. The antioxidants were enhanced by the intervention of the NCHDH and NTHDH and the level of the MDA and POD were attenuated marginally compared to the LPS-induced group. The hematology study showed marked improvement and the reversal of the LPS-induced changes in blood composition compared to the negative control. The synthetic function of the liver and kidney were preserved in the NCHDH and NTHDH treated group compared to the LPS-induced group. The NCHDH and NTHDH markedly enhanced the Nrf2, HO-1 (Heme oxygenase-1), while attenuated the Keap1 and TRPV1 expression level as compared to LPS treated group. Furthermore, the NCHDH and NTHDH treatment showed marked increased in the mRNA expression level of the HSP70/90 proteins compared to the negative control.

Rare case of acute on chronic hepatic failure in a patient with multiple myeloma-associated amyloidosis.

Amyloidosis is the extracellular deposition of unique protein fibrils in different tissue organs. It is most commonly associated with B-cell malignancy such as multiple myeloma or Waldenstrom macroglobulinaemia. It involves the liver, heart, kidney, peripheral nerves and soft tissues. Liver however is affected, but clinically apparent disease is very rare. Hepatomegaly and mild elevation of alkaline phosphatase is the most common presentation in patients with liver involvement. Acute hepatic failure is a rare presentation with myeloma-induced amyloidosis. The diagnosis can be difficult requiring biopsy or sometimes special staining of the tissue. Management is still very challenging.

Blue rubber bleb nevus: a rare cause of GI bleeding-review of management.

Blue rubber bleb nevus syndrome (BRBNS) is a rare congenital vascular anomaly syndrome characterised by multifocal venous vascular malformations. It involves skin, central nervous systems, liver, muscles and gastrointestinal (GI) tract resulting in intestinal haemorrhage and anaemia. Patients with BRBNS experience severe chronic anaemia without any diagnosis requiring multiple transfusions and hospitalisations. BRBNS has a propensity for severe life-threatening bleeding. Skin and GI tract are the most commonly affected organs.

Ligand targeting and peptide functionalized polymers as non-viral carriers for gene therapy.

Polymeric gene carriers have been developed to deliver therapeutic genes for treating various genetic diseases. They may diminish the problems related with viral vectors in terms of safety, immunogenicity and mutagenesis. But inefficient endosomal release, cytoplasmic transport and nuclear entry are the main limiting issues in the usage of polymeric carriers. Different strategies have been proposed to functionalize gene carriers for individually overcoming these barriers. Towards this aim, various polymeric carriers have been developed and further modified with certain ligands and peptides to achieve properties like good cargo DNA protection, excellent colloidal stability, high cellular uptake efficiency, efficient endo/lysosome escape, efficient import into the nucleus and specificity to target cells. These multifunctional polymeric carriers are beneficial for efficient gene delivery. In this review, we provide a comprehensive summary of the interaction between gene and polymeric carriers and the mechanism and challenges of gene carriers. We also highlight and discuss the recent developments and advancements in the synthesis of ligand targeting and peptide functionalized gene carriers.

A progressively targeted gene delivery system with a pH triggered surface charge-switching ability to drive angiogenesis in vivo.

For clinical application of therapeutic gene delivery, it is urgent to develop safe and in vivo efficient delivery systems. Nowadays, gene delivery carriers based on functional peptides have attracted much attention due to their excellent biocompatibility, biodegradability and biological multifunctionality. In the present study, a star-shaped integrated functional peptide, polyhedral oligomeric silsesquioxane (POSS-(C-G-NLS-G-TAT)16, abbreviated as PP1), was synthesized through "thiol-ene" click chemistry between the TAT-G-NLS-G-C multifunctional peptide sequence and inorganic octa-diallyl POSS. Cationic PP1 was mixed with the pZNF580 plasmid to obtain stable binary gene complexes (BCPs) with membrane penetrating and nucleus targeting functions. In order to improve BCPs' biocompatibility, cellular uptake, and endosome escape, they were further modified using an anionic polymer of PLL-g-CAGW21%-g-Acon (n = 47%, 57% and 64%) having an EC targeting ligand (CAGW peptide) and a charge reversal moiety (cis-aconitic amide) through electrostatic absorption to obtain ternary gene complexes (TCPs). By adjusting the weight ratio of PP1/pZNF580 plasmid/PLL-g-CAGW21%-g-Acon to 5/1/1.25, TCPs-1 with n = 47%, TCPs-2 with n = 57% and TCPs-3 with n = 64% exhibited a neutral zeta potential and suitable particle size; thus they were used for further biological evaluation. Compared with BCPs (5/1 weight ratio of PP1/pZNF580 plasmid), TCPs exhibited high hemocompatibility and cytocompatibility; more interestingly, they also showed significantly enhanced gene delivery efficiency. The TCP groups achieved perfect transfection effects in the proliferation and migration of human umbilical vein endothelial cells (HUVECs), and especially high neovascularization in vitro and in vivo. Our results demonstrated that the high graft ratio of cis-aconitic amide provided benefits of high biocompatibility and gene delivery efficiency, and the TCPs-3 group showed the optimized transfection efficiency among the three groups. Importantly, HUVECs transfected with TCPs-3 exhibited an outstanding ability to enhance angiogenesis in vivo. In brief, this multifunctional ternary gene system with the EC targeting ligand and membrane penetrating, charge reversal and nucleus targeting functions is a promising platform for the transfection of HUVECs, and may be useful for the treatment of cardiovascular diseases in clinical applications.

A PEG-b-poly(disulfide-l-lysine) based redox-responsive cationic polymer for efficient gene transfection.

Gene therapy is concerned with the transfer of complement genes to functionally defective cells in a safe and directed manner for the treatment of the most challenging diseases. But safety issues and low transfection efficiency of the gene vectors are the major challenges, which need to be overcome. Recently, redox-responsive bioreducible polymers containing disulfide linkages have been considered as efficient gene vectors, owing to the selective degradation of the disulfide bond in the reducing environment of the cells. This enables spatiotemporal release of pDNA with no or minimum toxicity. Herein, we reported a bioreducible poly(ethyleneglycol)-b-poly(disulfide-l-lysine) cationic polymer (denoted as PEG-SSL) via a Michael addition reaction of poly(ethyleneglycol)tetraacrylate PEG(Ac)4 and the terminal amine group of poly(disulfide-l-lysine). PEG-SSL efficiently condensed the plasmid ZNF580 gene (pZNF580) forming nano-sized polyplexes (155 ± 4 to 285 ± 3 nm) with zeta potentials of 1.9 ± 0.1 to 26.7 ± 0.4 mV. PEG-SSL successfully retarded pZNF580 at a small polymer/pDNA weight ratio of 10/1 and higher. When exposed to a reducing environment of 5 mM DTT, it rapidly released genes even at higher weight ratios of the PEG-SSL polymer in the PEG-SSL/pDNA complexes. The PEG-SSL/pZNF580 complexes exhibited good stability when exposed to DNase I and efficiently protected pDNA from degradation. In vitro transfection and cytotoxicity were investigated in EA.hy926 cells. The results showed that PEG-SSL successfully delivered pZNF580 into the cells with less cytotoxicity compared to PEI25kDa. The flow cytometry and confocal scanning laser microscopy results indicated that PEG-SSL polyplexes exhibited good cellular uptake and nuclear co-localization rates. All these results implied that PEG-SSL had the potential as a non-viral vector for gene transfection.

Multifunctional gene delivery systems with targeting ligand CAGW and charge reversal function for enhanced angiogenesis.

Gene delivery systems with good biocompatibility and high transfection efficiency play a major role in the clinical application of gene therapy. It is of great interest to develop a functional anionic polymer to modify polycationic carriers for the purpose of improving their biocompatibility and gene delivery ability. Herein, we prepared three kinds of anionic polymers, i.e., cis-aconitic anhydride grafted poly(l-lysine) (PLCA), cis-aconitic anhydride and CAGW functional peptide grafted poly(l-lysine) (PLCA-CAGW), and succinic anhydride and CAGW peptide grafted poly(l-lysine) (PLSA-CAGW), and coated them onto binary gene complexes to obtain three ternary complexes, i.e., TCP-CA, TCP-CA-CAGW and TCP-SA-CAGW, respectively. These gene delivery systems were integrated with a specific functional peptide and smart polyplexes that enabled them to perform a desired function in response to pH changes in biological microenvironments. The results of the cell viability assay showed that the prepared anionic polymers could improve the biocompatibility of gene complexes. Gene expression at the mRNA and protein levels demonstrated that TCP-CA-CAGW enhanced the gene delivery efficiency, benefiting from the targeting CAGW peptide and charge reversal moiety (cis-aconitic amide), while TCP-SA-CAGW showed a relatively low transfection efficiency because of negatively charged PLSA-CAGW and its non-reversal function. The PLCA-CAGW shell in TCP-CA-CAGW possessed an aconitic acid group, EC targeting ligand and charge reversal cis-aconitic amide, which enabled the gene delivery systems to be neutral in blood circulation, but once in the acidic lysosomes, they became positively charged for improving lysosomal escape and nuclear localization. Importantly, the in vitro/vivo angiogenesis assay demonstrated that human umbilical vein endothelial cells transfected with TCP-CA-CAGW functionalized ternary complexes could obviously enhance vascularization. These multifunctional ternary complexes with functional smart anionic polymer shells possessed low cytotoxicity and high gene delivery efficiency, and this strategy may be a promising platform for cardiovascular gene therapy.

PCR Based Detection of Phase Variable Genes in Pakistani Based Clinical Helicobacter pylori Strains.

BACKGROUND: The distribution pattern of phase-variable genes varies from strain to strain and from region to region. The present study was carried out to investigate the distribution pattern of phase-variable genes within Pakistan-based Helicobacter pylori strains and to analyze and compare them with strains prevalent in other parts of the world. OBJECTIVES: To determine the distribution pattern of phase-variable genes in H. pylori strains circulating in Pakistan. PATIENTS AND METHODS: Biopsy samples were collected from 85 symptomatic patients suffering from various upper gastrointestinal tract symptoms. The biopsy specimens were chopped, then inoculated on H. pylori-specific media and incubated in a Campylobacter Gas Generating kit. Positive isolates were further confirmed via staining and biochemical procedures. Primers were designed for five phase-variable genes using OligoCalc, an oligonucleotide properties calculator (version 3.26) according to parameters stipulated in the literature. Polymerase chain reaction (PCR) was performed on all positive isolates to determine the presence or absence of phase-variable genes. RESULTS: On culturing, the prevalence of H. pylori infections in the samples was 44.7%. The prevalence was higher in females than in males, and it increased with age. PCR amplification revealed that the hsdR gene was present in 79% of samples, while the mod and ß-subunit genes were present in 16% and 30% of samples, respectively. The streptococcal M protein gene was found in 79%, while the fliP gene was prevalent in 56%. CONCLUSIONS: The distribution patterns of phase-variable genes in Pakistani H. pylori strains were found to be somewhat different. The dominant prevalence of the hsdR gene was an interesting finding, considering its role in bacterial defense in both micro- and macroenvironments.

Impact of tuberculosis treatment on health-related quality of life of pulmonary tuberculosis patients: a follow-up study.

BACKGROUND: At present, much of the attention within tuberculosis (TB) management is spent on microbiological cure, and its impact on health-related quality of life (HRQoL) is either undervalued or seldom considered. The aim of this study was to evaluate the impact of TB treatment on HRQoL of new smear positive pulmonary tuberculosis (PTB) patients. Moreover, we also aimed to determine whether the selected socio-demographic and clinical variables were predictive of variability in the HRQoL scores over time. METHODS: This was a prospective follow-up of new smear positive PTB patients who were diagnosed at the chest clinic of Penang General Hospital between March 2010 and February 2011. All eligible patients (i.e., a new case of smear positive PTB, literate and aged 18 years or above) were asked to self-complete the SF-36v2 questionnaire at the start of their treatment, and then subsequently after the intensive phase and at the end of the treatment. A score on a health domain or component summary measure that was less than 47 norm-based scoring (NBS) point was considered indicative of impaired function within that health domain or dimension. Likewise, an individual having mental component summary (MCS) score ≤ 42 NBS point was considered to be at the risk of depression. Repeated measures ANOVA test was performed to examine how the summary scores varied over time, and to determine whether independent variables were predictive of variability in the physical component summary (PCS) and MCS scores over time. RESULTS: A total of 216 patients completed the SF-36v2 questionnaire at the start of their treatment. Out of these, 177 and 153 completed the questionnaire at the second and third follow-ups, respectively. The mean PCS scores at the start of the treatment, after the intensive phase and at the end of treatment were 41.9 (SD 5.1), 45.8 (SD 4.8) and 46.0 (SD 6.9), respectively. Similarly, the mean MCS scores at the start of the treatment, after the intensive phase and at the end of the treatment were 39.9 (SD 7.3), 45.0 (SD 6.8) and 46.8 (SD 7.8), respectively. More than 23% of the patients were at the risk of depression at the end of their TB treatment. Patient's age and being a smoker were predictive of differences in the PCS scores. Similarly, monthly income, being a smoker and TB-related symptoms at the start of the treatment were predictive of differences in the MCS scores. CONCLUSION: Although HRQoL improved with the treatment, the scores on component summary measures showed compromised physical and mental health among study patients even at the end of their TB treatment.

Microcalorimetric method to assess phagocytosis: macrophage-nanoparticle interactions.

This study evaluated the use of isothermal microcalorimetry (ITMC) to detect macrophage-nanoparticle interactions. Four different nanoparticle (NP) formulations were prepared: uncoated poly(isobutyl cyanoacrylate) (PIBCA), polysorbate-80-coated PIBCA, gelatin, and mannosylated gelatin NPs. Changes in NP formulations were aimed to either enhance or decrease macrophage-NP interactions via phagocytosis. Alveolar macrophages were cultured on glass slabs and inserted in the ITMC instrument. Thermal activities of the macrophages alone and after titration of 100 µL of NP suspensions were compared. The relative interactive coefficients of macrophage-NP interactions were calculated using the heat exchange observed after NP titration. Control experiments were performed using cytochalasin B (Cyto B), a known phagocytosis inhibitor. The results of NP titration showed that the total thermal activity produced by macrophages changed according to the NP formulation. Mannosylated gelatin NPs were associated with the highest heat exchange, 75.4 ± 7.5 J, and thus the highest relative interactive coefficient, 9,269 ± 630 M-1. Polysorbate-80-coated NPs were associated with the lowest heat exchange, 15.2 ± 3.4 J, and the lowest interactive coefficient, 890 ± 120 M-1. Cyto B inhibited macrophage response to NPs, indicating a connection between the thermal activity recorded and NP phagocytosis. These results are in agreement with flow cytometry results. ITMC is a valuable tool to monitor the biological responses to nano-sized dosage forms such as NPs. Since the thermal activity of macrophage-NP interactions differed according to the type of NPs used, ITMC may provide a method to better understand phagocytosis and further the development of colloidal dosage forms.

Response to standard interferon A2b and ribavirin combination therapy in chronic hepatitis C treatment naive patients.

BACKGROUND: Treatment of Chronic Hepatitis C is now well established with conventional interferon or pegylated interferon in combination with ribavirin. Peginterferon Alfa and Ribavirin for 6 to 12 months is currently approved initial therapy, which is expensive. Response of our patients to standard Interferon-alpha-2b and ribavirin for 24 weeks have been studied. The objective of this study was to asses Sustained Viral Response (SVR) with standard Interferon A2b and Ribavirin combination treatment in chronic Hepatitis C patients. METHODS: This quasi-experimental study was conducted at Combined Military Hospital, Quetta from Jan 2006 to Jun 2007. One hundred and three patients, with 20-60 years of age suffering from chronic Hepatitis C were selected on the basis of raised ALT, positive anti-HCV antibodies, evidence of viraemia by quantitative PCR for HCV RNA and liver biopsy. All patients were started on same brand of Interferon alpha-2b, 3 MIU subcutaneously, thrice weekly and oral Ribavirin (1,000-1,200 mg/day) for 24 weeks. End treatment response (ETR) after completion of treatment and SVR six months after ETR were recorded. RESULTS: The 103 patients, 85 males and 18 females with mean age of 21-48 years completed the treatment for 24 weeks. Mean ALT was 96.17 (SD +/- 49.98). End treatment response (ETR) was 89.3% (p = 0.032). Sustained Viral Response after 6 months of treatment was 86.4% (p = 0.034). CONCLUSION: Standard Interferon and Ribavirin had excellent SVR. It is effective as well as economical treatment in Chronic Hepatitis C patients.

Respiratory effects in people exposed to arsenic via the drinking water and tobacco smoking in southern part of Pakistan.

In this study, a survey has been conducted during 2005-2007 on surface and groundwater arsenic (As) contamination and its impact on the health of local population, of villages located on the banks of Manchar lake, southern part of Sindh, Pakistan. We have also assessed the relationship between arsenic exposure through respiratory disorders in male subjects with drinking water and smoking cigarettes made from tobacco grown in agricultural land irrigated with As contaminated lake water. The biological samples (blood and scalp hair) were collected from As exposed subjects (100% smokers) and age matched healthy male subjects (40.2% smoker and 59.8% non smokers) belong to unexposed areas for comparison purposes. The As concentration in drinking water (surface and underground water), agricultural soil, cigarette tobacco and biological samples were determined by electrothermal atomic absorption spectrometry. The range of As concentrations in lake water was 35.2-158 microg/L (average 97.5 microg/L), which is 3-15 folds higher than permissible limit of World Health Organization (WHO, 2004). While the As level in local cigarette tobacco was found to be 3-6 folds higher than branded cigarettes (0.37-0.79 microg/g). Arsenic exposed subjects (with and without RD) had significantly elevated levels of As in their biological samples as compared to referent male subject of unexposed area. These respiratory effects were more pronounced in individuals who had also As induced skin lesions. The linear regressions showed good correlations between As concentrations in water versus hair and blood samples of exposed subjects with and without respiratory problems.

The correlation of arsenic levels in drinking water with the biological samples of skin disorders.

Arsenic (As) poisoning has become a worldwide public health concern. The skin is quite sensitive to As and skin lesions are the most common and earliest nonmalignant effects associated to chronic As exposure. In 2005-2007, a survey was carried out on surface and groundwater arsenic contamination and relationships between As exposure via the drinking water and related adverse health effects (melanosis and keratosis) on villagers resides on the banks of Manchar lake, southern part of Sindh, Pakistan. We screened the population from arsenic-affected villages, 61 to 73% population were identified patients suffering from chronic arsenic toxicity. The effects of As toxicity via drinking water were estimated by biological samples (scalp hair and blood) of adults (males and females), have or have not skin problem (n=187). The referent samples of both genders were also collected from the areas having low level of As (<10 microg/L) in drinking water (n=121). Arsenic concentration in drinking water and biological samples were analyzed using electrothermal atomic absorption spectrometry. The range of arsenic concentrations in lake surface water was 35.2-158 microg/L, which is 3-15 folds higher than World Health Organization [WHO, 2004. Guidelines for drinking-water quality third ed., WHO Geneva Switzerland.]. It was observed that As concentration in the scalp hair and blood samples were above the range of permissible values 0.034-0.319 microg As/g for hair and <0.5-4.2 microg/L for blood. The linear regressions showed good correlations between arsenic concentrations in water versus hair and blood samples of exposed skin diseased subjects (R2=0.852 and 0.718) as compared to non-diseased subjects (R2=0.573 and 0.351), respectively.