An entropic theory of homogeneous ice nucleation in non-ionic aqueous solutions.

The nucleation of ice from aqueous solutions is a process essential to myriad environmental and industrial processes, but the physical factors affecting the capacity of different solutes to depress the homogeneous nucleation temperature of ice are yet poorly understood. In this work, we demonstrate that for many binary aqueous solutions of non-ionic solutes, this depression is dominated by the entropy of the liquid phase. Employing the classic Turnbull interpretation of the interfacial free energy γ∼TSliquid-Ssolid and estimating solution entropies with a Flory-style modification of the ideal entropy of mixing that accounts for solute size effects, we demonstrate that mixing entropy alone predicts experimental homogeneous nucleation temperatures across a wide variety of non-ionic solutions. We anticipate that this physical insight will not only enhance a fundamental understanding of homogeneous nucleation processes across fields but also open new avenues to the rational design of aqueous solutions for desired nucleation behaviors.

Encapsulated Rose Bengal Enhances the Photodynamic Treatment of Triple-Negative Breast Cancer Cells.

Among breast cancer subtypes, triple-negative breast cancer stands out as the most aggressive, with patients facing a 40% mortality rate within the initial five years. The limited treatment options and unfavourable prognosis for triple-negative patients necessitate the development of novel therapeutic strategies. Photodynamic therapy (PDT) is an alternative treatment that can effectively target triple-negative neoplastic cells such as MDA-MB-231. In this in vitro study, we conducted a comparative analysis of the PDT killing rate of unbound Rose Bengal (RB) in solution versus RB-encapsulated chitosan nanoparticles to determine the most effective approach for inducing cytotoxicity at low laser powers (90 mW, 50 mW, 25 mW and 10 mW) and RB concentrations (50 µg/mL, 25 µg/mL, 10 µg/mL and 5 µg/mL). Intracellular singlet oxygen production and cell uptake were also determined for both treatment modalities. Dark toxicity was also assessed for normal breast cells. Despite the low laser power and concentration of nanoparticles (10 mW and 5 µg/mL), MDA-MB-231 cells experienced a substantial reduction in viability (8 ± 1%) compared to those treated with RB solution (38 ± 10%). RB nanoparticles demonstrated higher singlet oxygen production and greater uptake by cancer cells than RB solutions. Moreover, RB nanoparticles display strong cytocompatibility with normal breast cells (MCF-10A). The low activation threshold may be a crucial advantage for specifically targeting malignant cells in deep tissues.

Influence of polyvinyl chloride microplastic on chromium uptake and toxicity in sweet potato.

The extensive use of plastic products and rapid industrialization have created a universal concern about microplastics (MPs). MPs can pose serious environmental risks when combined with heavy metals. However, current research on the combined effects of MPs and hexavalent chromium [Cr(VI)] on plants is insufficient. Herein, a 14-day hydroponic experiment was conducted to investigate the impact of PVC MPs (100 and 200 mg/L) and Cr(VI) (5, 10, and 20 µM) alone and in combination on sweet potato. Results showed that combined Cr(VI) and PVC MPs affected plant growth parameters significantly, but PVC MPs alone did not. The combined application of PVC MPs and Cr(VI) resulted in a decrease in plant height (24-65%), fresh biomass per plant (36-71%), and chlorophyll content (16-34%). Cr(VI) bioaccumulation increased with the increase in its doses, with the highest concentration of Cr(VI) in the leaves (16.45 mg/kg), stems (13.81 mg/kg), and roots (236.65 mg/kg). Cr(VI) and PVC MPs-induced inhibition varied with Cr(VI) and PVC MPs doses. Osmolytes and antioxidants, lipid peroxidation, and H2O2 contents were significantly increased, while antioxidant enzymes except CAT were decreased with increasing Cr(VI) concentration alone and mixed treatments. The presence of PVC MPs promoted Cr(VI) accumulation in sweet potato plants, which clearly showed severe toxic effects on their physio-biochemical characteristics, as indicated by a negative correlation between Cr(VI) concentration and these parameters. PVC MPs alone did not significantly inhibit these parameters. The findings of this study provide valuable implications for the proper management of PVC MPs and Cr(VI) in sweet potato plants.

First report of wheat dwarf bunt caused by Tilletia controversa Kühn in Pakistan.

Wheat (Triticum aestivum L.) is critical to food security worldwide. Wheat dwarf bunt is caused by Tilletia controversa Kühn and can cause 70-80% losses under severe condition (Trione et al. 1989; Xu et al., 2021). In May 2022, we observed dwarf bunt disease in six fields grown with spring cultivar (Glaxy-13) in District Swat, KPK-Pakistan. Infected plants had mottling and flecking on leaves, a greater number of tillers and were smaller than healthy plants. Diseased wheat head spikes were larger, wider and thicker, had bunted kernels (sori) filled with brown-black teliospores and a strong odor like that of rotten fish. Individual fields showed 10% infected plants while no dwarf bunt was recorded in nearby fields. About 150 heads exhibiting bunted kernels were collected among the six fields. Kernels were surface sterilized with 30% NaClO for 5 min after crushing by a centrifuge machine and washed with ddH20 three times. The teliospore suspension (1×106 spores/mL) was spread on 2% soil agar plates in a growth chamber (MLR 352 H, Panasonic, USA) and incubated at 5°C with 60% relative humidity for 60 days to test for T. controversa germination or at 16°C and 60% relative humidity for 15 days (MLR 352 H, Panasonic, USA) to test for T. caries and T. laevis germination. Teliospores germinated only on plates kept at 5°C. Teliospores were morphologically identified as a T. controversa from the infected samples. They ranged in size from 15.0 to 20.5 µm diam. and the walls had deep reticulations surrounded by a transparent sheath, differing from T. laevis which has smooth teliospores and T. caries which has no sheath and reticulations on the surface (Mathre 1996). To further confirm Tilletia spp. identification, genomic DNA of our two isolates (gmd123 and gmd1234) was obtained using an extraction kit (TransGen, Beijing, China). The internal transcribed spacer (ITS) region was amplified by using ITS1/4 (White et al. 1990). A BLAST search with GenBank accession no. OR366448 and OR366450 provided additional evidence the isolates belong to the complex of species that includes the three bunt species causing diseases on wheat, with 100% matches to verified sequences for T. controversa (eg. EU257561) but also to T. laevis and T. caries. Based on disease symptoms, teliospore morphology, germination at 5°C but not at 16°C, the bunt fungus was identified as T. controversa. To fulfill Koch's postulates, 10 mL (106 spores/mL) of germinated teliospores were injected into rhizosphere soil of Galaxy-13 cultivar at 2 leaves unfolded growth stage (Zadoks 12) and 2 mL (106 spores/mL) were injected into heads of same plants at growth stages Zadoks 61-65 with a syringe. Plants injected with sterile ddH2O were used as a control. Inoculated plants were grown in a growth chamber at 8°C with 50% humidity and 24 h light. After one month at the ripening stage, the bunted kernels of the inoculated plants were filled with black teliospores releasing a fishy smell, and the control plants did not have bunted kernels. Under an optical microscope, teliospores from the inoculated plants had reticulation surface and were measured 15 to 20.5 µm in diameter, similar to the teliospores of bunt heads from the fields. To the best of our knowledge, this is the first report of T. controversa causing dwarf bunt in district Swat, KPK-Pakistan. Because the pathogen is seedborne and soilborne, the disease may become a high risk to wheat production in Pakistan. Therefore, detection of this pathogen is very important to control the disease on time.

Investigation of Newly Synthesized Bis-Acyl-Thiourea Derivatives of 4-Nitrobenzene-1,2-Diamine for Their DNA Binding, Urease Inhibition, and Anti-Brain-Tumor Activities.

Bis-acyl-thiourea derivatives, namely N,N'-(((4-nitro-1,2-phenylene)bis(azanediyl)) bis(carbonothioyl))bis(2,4-dichlorobenzamide) (UP-1), N,N'-(((4-nitro-1,2-phenylene) bis(azanediyl))bis(carbonothioyl))diheptanamide (UP-2), and N,N'-(((4-nitro-1,2-phenylene)bis(azanediyl))bis(carbonothioyl))dibutannamide (UP-3), were synthesized in two steps. The structural characterization of the derivatives was carried out by FTIR, 1H-NMR, and 13C-NMR, and then their DNA binding, anti-urease, and anticancer activities were explored. Both theoretical and experimental results, as obtained by density functional theory, molecular docking, UV-visible spectroscopy, fluorescence (Flu-)spectroscopy, cyclic voltammetry (CV), and viscometry, pointed towards compounds' interactions with DNA. However, the values of binding constant (Kb), binding site size (n), and negative Gibbs free energy change (ΔG) (as evaluated by docking, UV-vis, Flu-, and CV) indicated that all the derivatives exhibited binding interactions with the DNA in the order UP-3 > UP-2 > UP-1. The experimental findings from spectral and electrochemical analysis complemented each other and supported the theoretical analysis. The lower diffusion coefficient (Do) values, as obtained from CV responses of each compound after DNA addition at various scan rates, further confirmed the formation of a bulky compound-DNA complex that caused slow diffusion. The mixed binding mode of interaction as seen in docking was further verified by changes in DNA viscosity with varying compound concentrations. All compounds showed strong anti-urease activity, whereas UP-1 was found to have comparatively better inhibitory efficiency, with an IC50 value of 1.55 ± 0.0288 µM. The dose-dependent cytotoxicity of the synthesized derivatives against glioblastoma MG-U87 cells (a human brain cancer cell line) followed by HEK-293 cells (a normal human embryonic kidney cell line) indicated that UP-1 and UP-3 have greater cytotoxicity against both cancerous and healthy cell lines at 400 µM. However, dose-dependent responses of UP-2 showed cytotoxicity against cancerous cells, while it showed no cytotoxicity on the healthy cell line at a low concentration range of 40-120 µM.

Photodynamic Treatment of Human Breast and Prostate Cancer Cells Using Rose Bengal-Encapsulated Nanoparticles.

Cancer, a prominent cause of death, presents treatment challenges, including high dosage requirements, drug resistance, poor tumour penetration and systemic toxicity in traditional chemotherapy. Photodynamic therapy, using photosensitizers like rose bengal (RB) with a green laser, shows promise against breast cancer cells in vitro. However, the hydrophilic RB struggles to efficiently penetrate the tumour site due to the unique clinical microenvironment, aggregating around rather than entering cancer cells. In this study, we have synthesized and characterized RB-encapsulated chitosan nanoparticles with a peak particle size of ~200 nm. These nanoparticles are readily internalized by cells and, in combination with a green laser (λ = 532 nm) killed 94-98% of cultured human breast cancer cells (MCF-7) and prostate cancer cells (PC3) at a low dosage (25 µg/mL RB-nanoparticles, fluence ~126 J/cm2, and irradiance ~0.21 W/cm2). Furthermore, these nanoparticles are not toxic to cultured human normal breast cells (MCF10A), which opens an avenue for translational applications.

Fabrication and characterization of chitosan nanoparticles using the coffee-ring effect for photodynamic therapy.

BACKGROUND AND OBJECTIVES: Biocompatible nanoparticles have been increasingly used in a variety of medical applications, including photodynamic therapy. Although the impact of synthesis parameters and purification methods is reported in previous studies, it is still challenging to produce a reliable protocol for the fabrication, purification, and characterization of nanoparticles in the 200-300 nm range that are highly monodisperse for biomedical applications. STUDY DESIGN/MATERIALS AND METHODS: We investigated the synthesis of chitosan nanoparticles in the 200-300 nm range by evaluating the chitosan to sodium tripolyphosphate (TPP) mass ratio and acetic acid concentration of the chitosan solution. Chitosan nanoparticles were also crosslinked to rose bengal and incubated with human breast cancer cells (MCF-7) to test photodynamic activity using a green laser (λ = 532 nm, power = 90 mW). RESULTS: We established a simple protocol to fabricate and purify biocompatible nanoparticles with the most frequent size occurring between 200 and 300 nm. This was achieved using a chitosan to TPP mass ratio of 5:1 in 1% v/v acetic acid at a pH of 5.5. The protocol involved the formation of nanoparticle coffee rings that showed the particle shape to be spherical in the first approximation. Photodynamic treatment with rose bengal-nanoparticles killed ~98% of cancer cells. CONCLUSION: A simple protocol was established to prepare and purify spherical and biocompatible chitosan nanoparticles with a peak size of ~200 nm. These have remarkable antitumor activity when coupled with photodynamic treatment.

Investigations on Anticancer Potentials by DNA Binding and Cytotoxicity Studies for Newly Synthesized and Characterized Imidazolidine and Thiazolidine-Based Isatin Derivatives.

Imidazolidine and thiazolidine-based isatin derivatives (IST-01-04) were synthesized, characterized, and tested for their interactions with ds-DNA. Theoretical and experimental findings showed good compatibility and indicated compound-DNA binding by mixed mode of interactions. The evaluated binding parameters, i.e., binding constant (Kb), free energy change (ΔG), and binding site sizes (n), inferred comparatively greater and more spontaneous binding interactions of IST-02 and then IST-04 with the DNA, among all compounds tested under physiological pH and temperature (7.4, 37 °C). The cytotoxic activity of all compounds was assessed against HeLa (cervical carcinoma), MCF-7 (breast carcinoma), and HuH-7 (liver carcinoma), as well as normal HEK-293 (human embryonic kidney) cell lines. Among all compounds, IST-02 and 04 were found to be cytotoxic against HuH-7 cell lines with percentage cell toxicity of 75% and 66%, respectively, at 500 ng/µL dosage. Moreover, HEK-293 cells exhibit tolerance to the increasing drug concentration, suggesting these two compounds are less cytotoxic against normal cell lines compared to cancer cell lines. Hence, both DNA binding and cytotoxicity studies proved imidazolidine (IST-02) and thiazolidine (IST-04)-based isatin derivatives as potent anticancer drug candidates among which imidazolidine (IST-02) is comparatively the more promising.

Astounding Health Benefits of Jamun (Syzygium cumini) toward Metabolic Syndrome.

Syzygium cumini, also called Jamun, or black plum, is an excellent source of bioactive components such as flavonoids, polyphenols, antioxidants, iron, and vitamin C. The Jamun tree is a tropical evergreen blooming plant and is an important medicinal plant from the Myrtaceae family that has been used for a long time in Indian and other traditional medicines across the world. Jamun is mainly cultivated in Asian countries such as Pakistan, India, Sri Lanka, and Bangladesh. Since ancient medicine, it has been utilized to treat a variety of diseases and physiological conditions. Currently, it is mostly used as a medication to treat various metabolic issues, including diabetes, hyperlipidemia, hypertension, obesity, etc. Therefore, Jamun could serve a beneficial role against metabolic syndrome (MS). In this work, the latest available scientific literature on Jamun was collected and the clinical trials investigating its effect on diabetes, hypertension, obesity, and hyperlipidemia were analyzed to find out how Jamun could improve the symptoms and biomarkers of MS. Overall, the results of this study found a significant association of Jamun with the prevention and treatment of these biomarkers of MS. In many studies, Jamun showed pharmacological modifications not only in MS but in many other diseases as well. Currently, its utilization as a folk medicine for the treatment of patients with MS is widely acknowledged. Hence, the findings of a large number of clinical studies confirmed the ameliorating effects of Jamun against MS due to its antioxidation, antidiabetic, anti-inflammation anticarcinogenic, and hyperlipidemic effects. More research is still needed to determine and identify the Jamun compounds and to elucidate their mechanisms of action that are responsible for these astounding bioactive properties and health benefits.

Pharmacological studies on the antinociceptive, anxiolytic and antidepressant activity of Tinospora crispa.

Pharmacological studies were performed in mice on the methanol extract of Tinospora crispa (TC), and of its hexane (HF) and chloroform (CF) fractions. Significant antinociceptive activity was observed for TC, HF, and CF in the acetic acid-induced writhing and formalin-induced paw licking tests. Anxiolytic and antidepressant activities were assessed using the open field, hole board, and elevated plus maze (EPM) tests. TC, HF, and CF demonstrated a significant decrease in spontaneous locomotor activity. They also showed an increase in the number of head-dippings in the hole-board test, suggesting decreased fearfulness. TC, and most of its fractions, showed a significant increase of the time spent in the opened arm of the EPM, indicating reduced anxiety. This study provides some support to explain the traditional use of T. crispa as a remedy for pain.

Epitope-Based Immunoinformatics Approach on Nucleocapsid Protein of Severe Acute Respiratory Syndrome-Coronavirus-2.

With an increasing fatality rate, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has emerged as a promising threat to human health worldwide. Recently, the World Health Organization (WHO) has announced the infectious disease caused by SARS-CoV-2, which is known as coronavirus disease-2019 (COVID-2019), as a global pandemic. Additionally, the positive cases are still following an upward trend worldwide and as a corollary, there is a need for a potential vaccine to impede the progression of the disease. Lately, it has been documented that the nucleocapsid (N) protein of SARS-CoV-2 is responsible for viral replication and interferes with host immune responses. We comparatively analyzed the sequences of N protein of SARS-CoV-2 for the identification of core attributes and analyzed the ancestry through phylogenetic analysis. Subsequently, we predicted the most immunogenic epitope for the T-cell and B-cell. Importantly, our investigation mainly focused on major histocompatibility complex (MHC) class I potential peptides and NTASWFTAL interacted with most human leukocyte antigen (HLA) that are encoded by MHC class I molecules. Further, molecular docking analysis unveiled that NTASWFTAL possessed a greater affinity towards HLA and also available in a greater range of the population. Our study provides a consolidated base for vaccine design and we hope that this computational analysis will pave the way for designing novel vaccine candidates.

Seroprevalence of Transplacentally acquired Measles antibodies in unvaccinated infants at nine months of age and its relation to the feeding practices.

BACKGROUND: In recent years Pakistan has faced frequent measles outbreaks killing hundreds of children despite the availability of vaccine for decades. This study was undertaken to determine the persistence of maternal transferred measles antibody levels in infants before measles vaccination with relation to their feeding practices. METHODS: A cross sectional study was conducted at district Islamabad over 1 year between 1st October 2013 to 30th Sept. 2016. Any infant less than 9 months of age, not suffering from an acute or debilitating illness and not vaccinated was enrolled in the study. After taking written informed consent from parents / guardians, information was collected on a pretested questionnaire. About 3 cc venous blood was taken to quantify any measles IgG antibodies. Data was analyzed by using Epi Info 7.2 version. RESULTS: Three hundred eighty-four infants were enrolled and were divided into three age groups, 1-90, 91-180 and 181-270 days age groups. Mean age of infants was 4.4 months ±3.2 SD. Male to female ratio was 1.2:1. A level of maternal measles IgG antibodies ≥12 U/ml was taken as protective. Of total 384 infants, 91(24%) had protective measles antibody titters (> 12 U/ml). and 65 (73%) of them were on breast milk. Highest antibody levels were found in 1-90 days age group. Analysis showed that 181-270 days aged infants had 3.1875 more odds of having unprotected/ low levels of antibodies against measles than children aged less than 180 days. Age group < 180 days found to be statistically significant with protective IgG levels (OR: 3.1875, P value: < 0.000063). CONCLUSION: Measles protective antibodies were found in infants < 180 days age group. Breast feeding provides early protection against measles. Levels drop down to low levels immediately after birth and then after 06 months. It is, therefore, recommended that measles vaccination should be considered for administration at 6 months or even earlier if measles immunity is desired.

Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma.

Serum cytokines and chemokines may reflect tumor biology and host response in follicular lymphoma (FL). To determine whether the addition of these biological factors may further refine prognostication, 30 cytokines and chemokines were measured in pretreatment serum specimens from newly diagnosed FL patients (n = 209) and from 400 matched controls. Cytokine levels were correlated with clinical outcome in patients who were observed or received single agent rituximab, or those who received chemotherapy. Correlations with outcome in chemotherapy treated patients were further examined in a separate cohort of 183 South West Oncology Group (SWOG) patients and all patients were then included in a meta-analysis. Six cytokines were associated with outcome in the Molecular Epidemiology Resource (MER) after adjusting for the FL international prognostic index. In patients who were observed or treated with rituximab alone, increased serum IL-12 and interleukin 1 receptor antagonist (IL-1RA) (P = .005 and .02) were associated with a shorter event-free survival. In patients receiving chemotherapy, hepatocyte growth factor, IL-8, IL-1RA, and CXCL9 (P = .015, .048, .004, and .0005) predicted a shorter EFS. When the MER chemotherapy treated patients and SWOG patients were combined in a meta-analysis, IL-2R, IL-1RA, and CXCL9 (P = .013, .042, and .0012) were associated with a poor EFS.

Success of an International Learning Health Care System in Hematopoietic Cell Transplantation: The American Society of Blood and Marrow Transplantation Clinical Case Forum.

The American Society for Blood and Marrow Transplantation (ASBMT) Clinical Case Forum (CCF) was launched in 2014 as an online secure tool to enhance interaction and communication among hematopoietic cell transplantation (HCT) professionals worldwide through the discussion of challenging clinical care issues. After 14 months, we reviewed clinical and demographical data of cases posted in the CCF from January 29, 2014 to March 18, 2015. A total of 137 cases were posted during the study period. Ninety-two cases (67%) were allogeneic HCT, 29 (21%) were autologous HCT, and in 16 (12%), the type of transplantation (autologous versus allogeneic) was still under consideration. The diseases most frequently discussed included non-Hodgkin lymphoma (NHL; n = 30, 22%), acute myeloid leukemia (n = 23, 17%), and multiple myeloma (MM; n = 20, 15%). When compared with the US transplantation activity reported by the US Department of Health and Human Services, NHL and acute lymphoblastic leukemia cases were over-represented in the CCF, whereas MM was under-represented (P < .001). A total of 259 topics were addressed in the CCF with a median of 2 topics/case (range, 1 to 6). Particularly common topics included whether transplantation was indicated (n = 57, 41%), conditioning regimen choice (n = 44, 32%), and post-HCT complications after day 100 (n = 43, 31%). The ASBMT CCF is a successful tool for collaborative discussion of complex cases in the HCT community worldwide and may allow identification of areas of controversy or unmet need from clinical, educational and research perspectives.

Bortezomib-induced acute pancreatitis: Case report and review of the literature.

Acute pancreatitis is a rare complication of chemotherapy agents. We describe the case of a patient with multiple myeloma who developed acute pancreatitis after treatment with bortezomib, a proteasome inhibitor commonly used in the treatment of this disease. We reviewed the available medical literature on this topic, and found other seven similar cases, all after intravenous bortezomib. Our case is the first one occurring with the subcutaneous route of administration.

Effect of GSTP1 and ABCC4 gene polymorphisms on response and toxicity of cyclophosphamide-epirubicin-5-fluorouracil-based chemotherapy in Bangladeshi breast cancer patients.

The most important cytotoxic drug namely, cyclophosphamide used in breast cancer along with epirubicin and 5-fluorouracil, is transported by ABCC transporters and detoxified by glutathione S-transferases (GSTs). The activities of these enzymes and transporters may vary in different population due to the presence of genetic polymorphisms. This study was aimed to evaluate the effects of GSTP1rs1695 and ABCC4rs9561778 polymorphisms on the response and toxicities produced by chemotherapy used in the treatment of Bangladeshi breast cancer patients. A total of 200 and 56 patients with invasive breast cancers were recruited from different public and private hospitals of Bangladesh of which 117 patients received neoadjuvant chemotherapy to examine the response as well as the toxicity, and another 139 patients received adjuvant chemotherapy to evaluate only the toxicity. Genetic polymorphisms of the mentioned genes were detected by using Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR RFLP). Patients carrying AG and AG plus GG genotype of GSTP1rs1695 were more likely to have a good response, whereas no association of ABCC4rs9561778 was found with the chemotherapy response. Patients carrying GT and GT plus TT genotypes of ABCC4rs9561778 were found to be associated with anemia, neutropenia, leukopenia, and gastrointestinal toxicities when compared with GG genotype whereas no association was found with thrombocytopenia. GSTP1rs1695 was not associated with any type of toxicities investigated. Our result indicates that GSTP1rs1695 polymorphism was strongly associated with the response of chemotherapy, whereas ABCC4rs9561778 polymorphism was significantly related with chemotherapy-induced toxicities.

IgM MGUS associated with anti-MAG neuropathy: a single institution experience.

Anti-MAG neuropathy is a very rare form of acquired polyneuropathy associated with IgM monoclonal gammopathy of undetermined significance (MGUS). We conducted a retrospective review of 194 consecutive MGUS patients seen at the Penn State Hershey Cancer Institute. We identified six patients among 37 (16 %) with IgM MGUS with anti-MAG neuropathy. Interestingly, an additional patient had anti-MAG neuropathy without MGUS. Common clinical manifestations were numbness and paresthesias of the extremities and gait imbalance. All four patients treated with rituximab and none of the three untreated ones had a subjective improvement of their symptoms. We conclude that all patients with IgM MGUS and neuropathy should be screened for anti-MAG antibodies and, if positive, they should be offered treatment with rituximab.

Effects of organic extracts and their different fractions of five Bangladeshi plants on in vitro thrombolysis.

BACKGROUND: The increasingly high incidence of ischemic stroke caused by thrombosis of the arterial vessels is one of the major factors that threaten people's health and lives in the world. The present treatments for thrombosis are still unsatisfactory. Herbal preparations have been used since ancient times for the treatment of several diseases. The aim of this study was to investigate whether herbal preparations possess thrombolytic activity or not. METHODS: An in vitro thrombolytic model was used to check the clot lysis effect of the crude extracts and fractions of five Bangladeshi plant viz., Trema orientalis L., Bacopa monnieri L., Capsicum frutescens L., Brassica oleracea L. and Urena sinuata L. using streptokinase as a positive control and water as a negative control. Briefly, venous blood drawn from twenty healthy volunteers was allowed to form clots which were weighed and treated with the test plant materials to disrupt the clots. Weight of clot after and before treatment provided a percentage of clot lysis. RESULTS: Using an in vitro thrombolytic model, different fractions of five Bangladeshi medicinal plants namely T. orientalis, B. monnieri, C. frutescens, B. oleracea and U. sinuata showed various range of clot lysis activity. Chloroform fractions of T. orientalis, B. monnieri, C. frutescens, B. oleracea and U. sinuata showed highest significant (P < 0.05 and P < 0.001) clot lysis activity viz., 46.44 ± 2.44%, 48.39 ± 10.12%, 36.87 ± .27%, 30.24 ± 0.95% and 47.89 ± 6.83% respectively compared with positive control standard streptokinase (80.77 ± 1.12%) and negative control sterile distilled water (5.69 ± 3.09%). Other fractions showed moderate to low clot lysis activity. Order of clot lysis activity was found to be: Streptokinase > Chloroform fractions > Methanol (crude) extract > Hydro-methanol fractions > Ethyl acetate fractions > n-hexane fractions > Water. CONCLUSIONS: Our study suggests that thrombolytic activity of T. orientalis, B. monnieri and U. sinuata could be considered as very promising and beneficial for the Bangladeshi traditional medicine. Lower effects of other extracts might suggest the lack of bio-active components and/or insufficient quantities in the extract. In vivo clot dissolving property and active component(s) of T. orientalis and B. monnieri for clot lysis could lead the plants for their therapeutic uses. However, further work will establish whether or not, chloroform soluble phytochemicals from these plants could be incorporated as a thrombolytic agent for the improvement of the patients suffering from atherothrombotic diseases.

Emergency care of traumatic brain injuries in Pakistan: a multicenter study.

BACKGROUND: This study assessed factors associated with emergency care outcomes and out-of-pocket treatment costs in traumatic brain injury (TBI) patients in Pakistan. METHODS: Data on TBI patients were extracted from a four-month surveillance study conducted in the emergency departments (ED) of seven large teaching hospitals. Emergency care access to physicians and imaging facilities were compared with respect to ED outcomes (discharged, admitted or dead). Out-of-pocket treatment costs (in United States dollars [USD]) were compared among different patient strata. RESULTS: ED outcomes were available for 1,787 TBI patients. Of them, most were males (79%), aged <25 years (46%) and arrived by ambulances (32%). Nurses or paramedical staff saw almost all patients (95%). Physicians with practice privileges (medical officers, residents or consultants) saw about half (55%) of them. Computerized tomography (CT) scans were performed in two of five patients (40%). Of all, 26% (n = 460) were admitted and 3% died (n = 52). Emergency care factors significantly associated with being admitted or died were arriving by ambulance (adjusted odds ratio [aOR] = 2.37, 95% confidence interval (CI) [95%CI] = 1.78-3.16); seen by medical officer/residents (aOR = 2.11; 95%CI = 1.49-2.99); and had CT scan (aOR = 2.93; 95%CI = 2.25-3.83). Out-of-pocket treatment costs at the ED were reported in 803 patients. Average costs were USD 8, (standard deviation [SD] = 23). Costs were twice as high in those arriving in ambulances (USD 20, SD = 49) or who underwent CT scans (USD 16, SD = 37). CONCLUSION: TBI patients' access to ambulance transport, experienced physicians, and imaging facilities during emergency care needs to be improved in Pakistan.

Uncovering the burden of intentional injuries among children and adolescents in the emergency department.

INTRODUCTION: In low- and middle-income countries, injuries are a leading cause of mortality in children. Much work has been done in the context of unintentional injuries but there is limited knowledge about intentional injuries among children. The objective of this paper was to understand the characteristics of children with intentional injuries presenting to emergency departments in Pakistan. METHODS: The data was from the Pakistan National Emergency Departments Surveillance (Pak-NEDS), conducted from November 2010 to March 2011 in seven major emergency departments of Pakistan. Data on 30,937 children under 18 years of age was collected. This paper reports frequency of intentional injuries and compares patient demographics, nature of injury, and discharge outcome for two categories of intentional injuries: assault and self-inflicted injuries. RESULTS: Intentional injuries presenting to the emergency departments (EDs) accounted for 8.2% (2551/30,937) amongst all other causes for under 18 years. The boy to girl ratio was 1:0.35. Intentional injuries included assault (n = 1679, 65.8%) and self-inflicted injuries (n = 872, 34.2%). Soft tissue injuries were most commonly seen in assault injuries in boys and girls but fractures were more common in self-inflicted injuries in both genders. CONCLUSION: Intentional injury is one of the reasons for seeking emergency treatment amongst children and a contributor to morbidity in EDs of Pakistan. Moreover, such injuries may be underestimated due to lack of reporting and investigative resources. Early identification may be the first step leading to prevention.