Extremely Low-Frequency Magnetic Field Enhances the Therapeutic Efficacy of Low-Dose Cisplatin in the Treatment of Ehrlich Carcinoma

e present study examines the therapeutic efficacy of the administration of low-dose cisplatin (cis) followed by exposure to extremely low-frequency magnetic �eld (ELF-MF), with an average intensity of 10 mT, on Ehrlich carcinoma in vivo. e cytotoxic and genotoxic actions of this combination were studied using comet assay, mitotic index (MI), and the induction of micronucleus (MN). Moreover, the inhibition of tumor growth was also measured. Treatment with cisplatin and ELF-MF (group A) increased the number of damaged cells by 54% compared with 41% for mice treated with cisplatin alone (group B), 20% for mice treated by exposure to ELF-MF (group C), and 9% for the control group (group D). Also the mitotic index decreased signi�cantly for all treated groups ( ). e decrement percent for the treated groups (A, B, and C) were 70%,65%, and 22%, respectively, compared with the control group (D). Additionally, the rate of tumor growth at day 12 was suppressed signi�cantly ( ) for groups A, B, and C with respect to group (D). ese results suggest that ELF-MF enhanced the cytotoxic activity of cisplatin and potentiate the bene�t of using a combination of low-dose cisplatin and ELF-MF in the treatment of Ehrlich carcinoma

Assessment of Genotoxic and Cytotoxic Hazards in Brain and Bone Marrow Cells of Newborn Rats Exposed to Extremely Low-Frequency Magnetic Field

The present study aimed to evaluate the association between whole body exposure to extremely low frequency magnetic field (ELF-MF) and genotoxic , cytotoxic hazards in brain and bone marrow cells of newborn rats. Newborn rats (10 days after delivery) were exposed continuously to 50 Hz, 0.5 mT for 30 days. The control group was treated as the exposed one with the sole difference that the rats were not exposed to magnetic field. Comet assay was used to quantify the level of DNA damage in isolated brain cells. Also bone marrow cells were flushed out to assess micronucleus induction and mitotic index. Spectrophotometric methods were used to measure the level of malondialdehyde (MDA) and the activity of glutathione (GSH) and superoxide dismutase (SOD). The results showed a significant increase in the mean tail moment indicating DNA damage in exposed group (P<0.01,0.001,0.0001). Moreover ELF-MF exposure induced a significant (P<0.01,0.001) four folds increase in the induction of micronucleus and about three folds increase in mitotic index (P<0.0001). Additionally newborn rats exposed to ELF-MF showed significant higher levels of MDA and SOD (P<0.05). Meanwhile ELF-MF failed to alter the activity of GSH. In conclusion, the present study suggests an association between DNA damage and ELF-MF exposure in newborn rats

Factors Associated with Klebsiella

Although Klebsiella bacteremia in children is perceived to be associated with fatal consequences, data are scarce on those children presenting with diarrhea. We evaluated the factors associated with Klebsiella bacteremia in such children. In this retrospective chart analysis, data of all diarrheal children was retrieved from electronic medical record system (named as SHEBA) of Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), from January 1, 2010, to December 31, 2012, who had their blood culture done. This was a study having a case-control design where comparison of clinical and laboratory characteristics was done among children with Klebsiella bacteremia (cases = 30) and those without any bacteraemia (controls = 90). Controls were selected randomly. The cases more often had fatal outcome (p<0.001). In logistic regression analysis, after adjusting for potential confounders such as young age, severe dehydration, severe wasting, abnormal mentation, hypotension, and fast breathing, the cases were independently associated with hospital-acquired infection and positive stool growth (for all, p<0.05). The study highlights the importance of obtaining blood cultures in hospitalized children under five years old with diarrheal illness in the presence of either hospital-acquired infection or positive stool culture to have better outcome

Emergence of mobile colistin resistance (mcr-8) in a highly successful Klebsiella pneumoniae sequence type 15 clone from clinical infections in Bangladesh

The emergence of mobilized colistin resistance genes (mcr) has become a serious concern in clinical practice, compromising treatment options for life-threatening infections. In this study, colistin-resistant Klebsiella pneumoniae harboring mcr-8.1 was recovered from infected patients in the largest public hospital of Bangladesh, with a prevalence of 0.3% (3/1,097). We found mcr-8.1 in an identical highly stable multidrug-resistant IncFIB(pQil) plasmid of ∼113 kb, which belonged to an epidemiologically successful K. pneumoniae clone, ST15. The resistance mechanism was proven to be horizontally transferable, which incurred a fitness cost to the host. The core genome phylogeny suggested the clonal spread of mcr-8.1 in a Bangladeshi hospital. Core genome single-nucleotide polymorphisms among the mcr-8.1-positive K. pneumoniae isolates ranged from 23 to 110. It has been hypothesized that mcr-8.1 was inserted into IncFIB(pQil) with preexisting resistance loci, blaTEM-1b and blaCTX-M-15, by IS903B. Coincidentally, all resistance determinants in the plasmid [mcr-8.1, ampC, sul2, 1d-APH(6), APH(3′′)-Ib, blaTEM-1b, blaCTX-M-15] were bracketed by IS903B, demonstrating the possibility of intra- and interspecies and intra- and intergenus transposition of entire resistance loci. This is the first report of an mcr-like mechanism from human infections in Bangladesh. However, given the acquisition of mcr-8.1 by a sable conjugative plasmid in a successful high-risk clone of K. pneumoniae ST15, there is a serious risk of dissemination of mcr-8.1 in Bangladesh from 2017 onwards

Classification of patients with knee osteoarthritis in clinical phenotypes: data from the osteoarthritis initiative

<div><p>Objectives</p><p>The existence of phenotypes has been hypothesized to explain the large heterogeneity characterizing the knee osteoarthritis. In a previous systematic review of the literature, six main phenotypes were identified: Minimal Joint Disease (MJD), Malaligned Biomechanical (MB), Chronic Pain (CP), Inflammatory (I), Metabolic Syndrome (MS) and Bone and Cartilage Metabolism (BCM). The purpose of this study was to classify a sample of individuals with knee osteoarthritis (KOA) into pre-defined groups characterized by specific variables that can be linked to different disease mechanisms, and compare these phenotypes for demographic and health outcomes.</p><p>Methods</p><p>599 patients were selected from the OAI database FNIH at 24 months’ time to conduct the study. For each phenotype, cut offs of key variables were identified matching the results from previous studies in the field and the data available for the sample. The selection process consisted of 3 steps. At the end of each step, the subjects classified were excluded from the further classification stages. Patients meeting the criteria for more than one phenotype were classified separately into a ‘complex KOA’ group.</p><p>Results</p><p>Phenotype allocation (including complex KOA) was successful for 84% of cases with an overlap of 20%. Disease duration was shorter in the MJD while the CP phenotype included a larger number of Women (81%). A significant effect of phenotypes on WOMAC pain (F = 16.736 p <0.001) and WOMAC physical function (F = 14.676, p < 0.001) was identified after controlling for disease duration.</p><p>Conclusion</p><p>This study signifies the feasibility of a classification of KOA subjects in distinct phenotypes based on subgroup-specific characteristics.</p></div

Annexin A6 improves anti-migratory and anti-invasive properties of tyrosine kinase inhibitors in EGFR overexpressing human squamous epithelial cells

Annexin A6 (AnxA6), a member of the calcium (Ca2+ ) and membrane binding annexins, is known to stabilize and establish the formation of multifactorial signaling complexes. At the plasma membrane, AnxA6 is a scaffold for protein kinase Cα (PKCα) and GTPase-activating protein p120GAP to promote downregulation of epidermal growth factor receptor (EGFR) and Ras/mitogen-activated protein kinase (MAPK) signaling. In human squamous A431 epithelial carcinoma cells, which overexpress EGFR, but lack endogenous AnxA6, restoration of AnxA6 expression (A431-A6) promotes PKCα-mediated threonine 654 (T654)-EGFR phosphorylation, which inhibits EGFR tyrosine kinase activity. This is associated with reduced A431-A6 cell growth, but also decreased migration and invasion in wound healing, matrigel, and organotypic matrices. Here, we show that A431-A6 cells display reduced EGFR activity in vivo, with xenograft analysis identifying increased pT654-EGFR levels, but reduced tyrosine EGFR phosphorylation compared to controls. In contrast, PKCα depletion in A431-A6 tumors is associated with strongly reduced pT654 EGFR levels, yet increased EGFR tyrosine phosphorylation and MAPK activity. Moreover, tyrosine kinase inhibitors (TKIs; gefitinib, erlotinib) more effectively inhibit cell viability, clonogenic growth, and wound healing of A431-A6 cells compared to controls. Likewise, the ability of AnxA6 to inhibit A431 motility and invasiveness strongly improves TKI efficacy in matrigel invasion assays. This correlates with a greatly reduced invasion of the surrounding matrix of TKI-treated A431-A6 when cultured in 3D spheroids. Altogether, these findings implicate that elevated AnxA6 scaffold levels contribute to improve TKI-mediated inhibition of growth and migration, but also invasive properties in EGFR overexpressing human squamous epithelial carcinoma

Annexin A6 and NPC1 regulate LDL-inducible cell migration and distribution of focal adhesions

Cholesterol is considered indispensable for cell motility, but how physiological cholesterol pools enable cells to move forward remains to be clarified. The majority of cells obtain cholesterol from the uptake of Low-Density lipoproteins (LDL) and here we demonstrate that LDL stimulates A431 squamous epithelial carcinoma and Chinese hamster ovary (CHO) cell migration and invasion. LDL also potentiated epidermal growth factor (EGF) -stimulated A431 cell migration as well as A431 invasion in 3-dimensional environments, using organotypic assays. Blocking cholesterol export from late endosomes (LE), using Niemann Pick Type C1 (NPC1) mutant cells, pharmacological NPC1 inhibition or overexpression of the annexin A6 (AnxA6) scaffold protein, compromised LDL-inducible migration and invasion. Nevertheless, NPC1 mutant cells established focal adhesions (FA) that contain activated focal adhesion kinase (pY397FAK, pY861FAK), vinculin and paxillin. Compared to controls, NPC1 mutants display increased FA numbers throughout the cell body, but lack LDL-inducible FA formation at cell edges. Strikingly, AnxA6 depletion in NPC1 mutant cells, which restores late endosomal cholesterol export in these cells, increases their cell motility and association of the cholesterol biosensor D4H with active FAK at cell edges, indicating that AnxA6-regulated transport routes contribute to cholesterol delivery to FA structures, thereby improving NPC1 mutant cell migratory behaviour

Time-series analysis of long-term photometry of BM Canum Venaticorum

Long-term photometry is commonly used to monitor chromospheric activity of late-type stars. We study standard Johnson differential V photometry of the RS CVn binary BM Canum Venaticorum (BM CVn) spanning over a quarter of a century. Our main aims are to determine the activity cycles, the rate of surface differential rotation, and the rotation period of the active longitudes of BM CVn. The continuous period search (CPS) algorithm is applied to the photometry. The changes of the mean and amplitude of the light curves are used to search for activity cycles. The rotation period changes give an estimate of the rate of surface differential rotation. The Kuiper method is applied to the epochs of the primary and secondary minima to search for active longitudes. The photometry reveals the presence of a stable mean light curve (MLC) connected to the orbital period P-orb=20.(d)6252 of this binary. We remove this MLC from the original V magnitudes, which gives us the corrected V magnitudes. These two samples of Vand Vdata are analyzed separately with CPS. The fraction of unreliable CPS models decreases when the MLC is removed. The same significant activity cycle of approximately 12.5 years is detected in both V and V samples. The estimate for the surface differential rotation coefficient, k >= 0.10, is the same for both samples, but the number of unrealistic period estimates decreases after removing the MLC. The same active longitude period of P-al=20.(d)511 +/- 0.(d)005 is detected in the V and V magnitudes. This long-term regularity in the epochs of primary and secondary minima of the light curves is not caused by the MLC. On the contrary, the MLC hampers the detection of active longitudes.Peer reviewe

Outbreak of hypervirulent multi-drug resistant Klebsiella variicola causing high mortality in neonates in Bangladesh

We report an outbreak by MDR K. variicola clone (ST771) in a Bangladeshi neonatal unit from October, 2016 to January, 2017, associated with high mortality (54.5%). During the outbreak, K. variicola ST771 acquired MDR plasmid harbouring blaNDM-1, linked to high exposure to ceftriaxone and amikacin in the NICU of DMCH

COVID-19 among staff and their family members of a healthcare research institution in Bangladesh between March 2020 and April 2021 : a test-negative case–control study

Objective To identify factors associated with COVID- 19 positivity among staff and their family members of icddr,b, a health research institute located in Bangladesh. Setting Dhaka, Bangladesh. Participants A total of 4295 symptomatic people were tested for SARS-CoV-2 by reverse-transcription PCR between 19 March 2020 and 15 April 2021. Multivariable logistic regression was done to identify the factors associated with COVID- 19 positivity by contrasting test positives with test negatives. Result Forty-three per cent of the participants were tested positive for SARS-CoV-2. The median age was high in positive cases (37 years vs 34 years). Among the positive cases, 97% were recovered, 2.1% had reinfections, 24 died and 41 were active cases as of 15 April 2021. Multivariable regression analysis showed that age more than 60 years (adjusted OR (aOR)=2.1, 95% CI 1.3 to 3.3; pwere tested negative. Conclusions The study findings suggest that older age, fever, cough and anosmia were associated with COVID- 19 among the study participants.publishedVersionPeer reviewe