Breast Cancer in Younger and Older Women: A Comparison of Clinicopathological Traits.

Breast cancer stands as the prevailing invasive cancer globally, bearing high mortality rates among women. Existing evidence indicates diminished survival rates in younger patients. Consequently, this study endeavors to assess and contrast the pathological features of breast cancer in women under 40 years of age with their older counterparts. Conducted as a cross-sectional analysis, this study encompasses 560 patients diagnosed with breast cancer, seeking treatment at Mymensingh Medical College Hospital (MMCH), Community Based Medical College Bangladesh (CBMCB) and several private hospitals in Mymensingh. The gathered data incorporates information such as age, residential area, occupation, tumor histopathology, TNM classification, staging and status of hormone receptor. The patients' mean age (standard deviation) was 49.7±11.9 years, with 20.5% below 40, most were from rural areas and were housewives. Ductal carcinoma prevailed as the most common histopathologic type (87.67%). However, younger patients exhibited a higher prevalence of lobular and other rare carcinomas compared to their older counterparts (p=0.04). Additionally, the younger group demonstrated larger tumor sizes (p=0.01), lymphatic node involvement (p=0.04) and advanced staging (p=0.004). Notably, younger age showed more negativity for estrogen and/or progesterone receptors. The results suggested that women under 40 years old exhibit more aggressive tumor characteristics and a more severe form of breast cancer compared to their older counterparts.

Procalcitonin versus C-Reactive Protein as a Biomarker for Prediction of Bacterial Infection in Children with Febrile Neutropenia in Acute Leukemia.

Febrile neutropenia (FN) is a frequently occurring treatment-related complication with significant morbidity and mortality for childhood acute leukemia. Early diagnosis and assessment of severity are essential steps for early comprehensive treatment to reduce FN-related morbidity and mortality. Biomarkers like C-reactive protein (CRP) and procalcitonin (PCT) can be used to assess and predict the bacterial infection in children with febrile neutropenia. The objective of the study was to determine the role of procalcitonin and CRP as a biomarker for prediction of bacterial infection in children with FN in acute leukemia. This prospective observational study was conducted in the Department of Pediatric Hematology and Oncology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh from August 2020 to July 2021. Total 58 Children with acute leukemia aged 1 to <18 years with FN were analyzed in this study. A proper history and thorough physical examination were carried out. The blood sample was sent for biomarkers (Procalcitonin and CRP) within 24 hours of the onset of FN and other investigations, such as Complete blood count, Blood C/S, Urine R/E and C/S. Metabolic workup (SGPT, Serum Creatinine, Serum Electrolytes, Serum Ca+) was also done in every patient. Stool R/E & C/S, Chest X-ray, Wound swab for C/S were done when the patient presented with diarrhoea, cough, respiratory distress and focal sepsis respectively. In this study, the mean age of the patients was 6.62±4.07 years (1.10-16.0 years) and 34 patients (58.6%) were male. In 65.5% of patients, localizing signs of infection were not identified. Of the 58 patients, 12 patients (20.7%) showed positive blood culture and 2 patients (3.4%) showed positive urine culture. Klebsiella spp (41.0%) was the most frequent organism isolated followed by Acinetobacter (17.0%), Pseudomonas (17.0%) and E. coli (17.0%). The median PCT levels were significantly higher in patients with bacterial infection than patients without bacteremia (26.10µg/l versus 0.78µg/l, p=0.002) and PCT level >2µg/l was significantly associated with bacteremia. The median CRP levels in the bacteremia and without-bacteremia patients were 137.4mg/L and 54.17mg/L, respectively (p=0.036). In direct comparisons, PCT showed better overall performance than CRP with the AUC being 0.797 (95% CI 0.651-0.943) for PCT and 0.697 (95% CI 0.54-0.855) for CRP in predicting the bacterial infection. PCT and CRP both are useful biomarkers for the prediction of bacteremia, but PCT may be a superior early biomarker as compared to CRP to predict bacterial infection in children with febrile neutropenia in acute leukemia.

Comparative Study between Acacia Nilotica versus Povidone Iodine in Topical Treatment of Omphalocele Major.

Well established and common practice in conservative management of omphalocele major is escharotics therapy with different topical agents. Among them mercurochrome, alcohol, silver salts, povidone iodine, acacia nilotca paste are commonly used. It is a comparative study between application of acacia nilotica paste and povidone iodine solution as a primary non surgical treatment of omphalocele major regarding efficacy and safety of these two topical agents. A double blind randomized controlled study was conducted at the department of Paediatric Surgery, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from July 2016 to June 2019. In this study 20 cases of omphalocele major and randomly divided into two equal groups. Group A and Group B treated with acacia nilotica paste and povidone iodine solution respectively. Gastroschisis, ruptured-omphalocele major or omphalocele minor excluded in this study. The size of the fascial defect in cm, time required for full oral feeding tolerance and duration of hospital stay were evaluating parameters. Patients with Group A tolerated full oral feeding earlier, shorter total hospital stay duration and low mortality rate than those from Group B. Application of acacia nilotica is a safe and effective treatment of omphalocele major regarding rapid full oral feeding tolerance, shorter hospital stay and low mortality rate.

Platelet Count as a Prognostic Factor in Stage IV Non-Small Cell Lung Cancer.

Increase platelet count can accompany various cancers including lung cancer. This finding has recently been suggested to indicate poor prognosis. In patients with malignancies, thrombocytosis has previously been related disease stage, histological type and survival. In this study, the prevalence of thrombocytosis and the prognostic information provided by platelet count were analyzed in patients with stage IV Non-Small Cell Lung Cancer (NSCLC) with an aim to assess elevated platelet count as a prognostic factor in patients with stage IV NSCLC and to investigate whether there is relationship between thrombocytosis, other clinico-pathologic factors and median survival. This prospective observational study was conducted in National Institute of Cancer Research and Hospital (NICRH), Dhaka, Bangladesh from September 2019 to August 2020. A total of 108 patients were enrolled purposively. Detail history taking, thorough physical examination was done along with relevant investigations. Data were collected by semi structured questionnaire and analysis was done with the help of Statistical Package for Social Science (SPSS), version 21.0. The mean age of the patients was found 56.4±12.2 years with range from 35 to 75 years. Majority (79.6%) patients were male, 52.8% patients came from low income and 36.1% were farmer. Majority (40.7%) were symptomatic; in bed >50.0% of day. Almost two third (59.3%) had <5.0% weight loss. Almost three fourth (69.4%) had squamous cell carcinoma. At the time of first assessment 75(69.4%) patients had normal and 33(30.6%) had elevated platelet count level. Age, sex and histological type were statistically not significant between normal and elevated platelet count level groups. But performance status, weight loss were statistically significant (p<0.05) between two groups. According to univariate analysis, age, performance status at presentation, weight loss more than 10.0% for 3 months and platelet count prior the start of treatment were all significant predictors for the overall survival. In multivariate analysis age, performance status at presentation and initial thrombocytosis were independent prognostic determinants for overall survival. Median survival time was significantly higher for the normal platelet count group and elevated platelet count group (7.5 months versus 5.5 months) respectively (95% CI, 5.5-7.5), p<0.001. The frequency of thrombocytosis in patients with stage-IV NSCLC at first presentation was 30.6% and median survival time in these patients was significantly shorter compared in patients without thrombocytosis. These results concluded that an elevated platelet count could be a useful prognostic factor for survival in patients with stage-IV NSCLC.

Solitary Rectal Ulcer Syndrome: A Rare and Often Misdiagnosed Cause of Rectal Bleeding in Children.

Solitary rectal ulcer syndrome (SRUS) is an uncommon benign rectal disorder. Typically, young adults are affected and it is rare in children. Straining during defecation, self-induced trauma and paradoxical contraction of puborectalis muscle are the major contributing factors of this condition. Clinical features of SRUS are rectal bleeding, mucorrhoea, excessive straining during defecation, tenesmus, feeling of incomplete defecation and constipation. A complete and thorough history is most important for diagnosis of SRUS. Rectal bleeding may be misinterpreted as originating from an anal fissure caused by constipation or as other causes of rectal bleeding such as a juvenile polyp. The best and most accurate diagnostic method of SRUS is rectal biopsy. The major histological feature of SRUS is fibromuscular obliteration of the lamina propria. Avoiding straining, regular toilet habit, use of bulk laxatives, steroid and sucralfate enemas are the mainstay of treatment. Biofeedback mechanism is another treatment option. Because the clinical presentation varies, the diagnosis requires a high index of suspicion for both the clinician and the pathologist.

Pattern of Glomerular Disease in a Tertiary Care Hospital of Bangladesh.

Glomerular disease is one of the most important causes of chronic kidney disease in developing countries like Bangladesh as well as the whole world. The pattern of glomerular disease varies in different countries and can have different clinical presentations. The aim of the study was to analyze the clinical profile and to determine the histological pattern of glomerular diseases in a large tertiary care hospital in Bangladesh. All kidney biopsies performed in Mymensingh Medical College Hospital, Bangladesh from October 2018 to March 2020 were prospectively analyzed in the study. A total of 101 patients with kidney biopsy were examined by clinical and laboratory findings and by light and immuno-fluorescence microscopy. The mean age was 30.0±14.6 years and 50(49.5%) were male and 51(50.5%) were female with a male to female ratio of 1:1. The clinical syndromes namely nephrotic syndrome, nephritic syndrome, nephrito-nephrotic presentation, RPGN like presentation, macroscopic haematuria and asymptomatic urine abnormality were present in 31.7%, 34.5%, 22.8%, 11.9%, 19.8% and 10.9% patients respectively. The most common histological varieties found in the study were mesangial proliferative glomerulonephritis (MesPGN) (18.8%) and focal segmental glomerulosclerosis (FSGS) (18.8%). Other histopathological pattern among the studied subjects revealed minimal change disease (MCD) in 5.9%, membranous nephropathy (MN) in 7.9%, membranoproliferative glomerulonephritis (MPGN) in 16.8%, IgA nephropathy in 5%, IgM nephropathy in 2%, IgG nephropathy in 2%, diffuse proliferative glomerulonephritis (DPGN) in 1%, focal proliferative glomerulo-nephritis (FPGN) in 3%, crescentic GN in 3%, lupus nephritis (LN) in 13.9%, amyloidosis in 1% and fibrillary glomerulopathy in 1% patient. The pattern of glomerular disease found in this study was similar to other studies performed in Bangladesh with a little variation. It may guide the future researchers to establish a national kidney biopsy registry in Bangladesh.

Prevalence of Organic Colonic Lesions by Colonoscopy in Patients with Irritable Bowel Syndrome Fulfilling Rome III Criteria.

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder usually diagnosed by using symptom-based diagnostic criteria. Recent evidence suggests the presence of organic diseases in some patients fulfilling the diagnostic criteria of IBS which may be missed unless investigations are performed. The aim of this cross-sectional study is to find out the prevalence of organic colonic lesions at colonoscopy in patients with IBS fulfilling the Rome III criteria.The study was conducted in the department of Gastroenterology OPD of the North East Medical College, Sylhet, Bangladesh from December 2016 to December 2017. Consecutive 153 patients of IBS diagnosed by validated Bangla version of ROME III criteria were included in this study. Colonoscopy was done for each patient and findings were recorded. Prevalence of colonic disease was compared between those meeting criteria for IBS, according to the presence or absence of co-existent alarm features, and by IBS subtype. A substantial number of patients 43(28.1%) fulfilling the Rome III criteria were found to have organic colonic lesions at colonoscopy. No significant difference was found regarding colonic lesions among patients with IBS symptoms with or without alarm features (p=0.876). Colonic polyp was the commonest findings in 19(12.1%) subjects at colonoscopy, followed by colonic ulcers in 16(10.5%) subjects. Organic colonic lesions are found to be more common among relatively older age group patients (p=0.011). A significant number of patients with symptoms compatible with IBS exhibited colonic lesions following investigation with a predilection towards older age. Careful clinical evaluation and relevant investigations are necessary to reduce diagnostic uncertainty.

Peptidoglycan-treated tumor antigen-pulsed dendritic cells impart complete resistance against tumor rechallenge.

Solid tumors elicit suppressive T cell responses which impair antigen-presenting cell (APC) functions. Such immune suppression results in uncontrolled tumor growth and mortality. Addressing APC dysfunction, dendritic cell (DC)-mediated anti-tumor vaccination was extensively investigated in both mice and humans. These studies never achieved full resistance to tumor relapse. Herein, we describe a repetitive RM-1 murine tumor rechallenge model for recurrence in humans. Using this newly developed model, we show that priming with tumor antigen-pulsed, Toll-like receptor (TLR)2 ligand-activated DCs elicits a host-protective anti-tumor immune response in C57BL/6 mice. Upon stimulation with the TLR2 ligand peptidoglycan (PGN), the tumor antigen-pulsed DCs induce complete resistance to repetitive tumor challenges. Intra-tumoral injection of PGN reduces tumor growth. The tumor resistance is accompanied by increased expression of interleukin (IL)-27, T-box transcription factor TBX21 (T-bet), IL-12, tumor necrosis factor (TNF)-α and interferon (IFN)-γ, along with heightened cytotoxic T lymphocyte (CTL) functions. Mice primed four times with PGN-stimulated tumor antigen-pulsed DCs remain entirely resistant to repeat challenges with RM-1 tumor cells, suggesting complete prevention of relapse and recurrence of tumor. Adoptive transfer of T cells from these mice, which were fully protected from RM-1 rechallenge, confers anti-tumor immunity to syngeneic naive recipient mice upon RM-1 challenge. These observations indicate that PGN-activated DCs induce robust host-protective anti-tumor T cells that completely resist tumor growth and recurrence.

Enhanced exudation of malate in the rhizosphere due to AtALMT1 overexpression in blackgram (Vigna mungo L.) confers increased aluminium tolerance.

Worldwide, 50% of soil is acidic, which induces aluminium (Al) toxicity in plants, as the phyto-availability of Al3+ increases in acidic soil. Plants responds to Al3+ toxicity by exuding organic acids into the rhizosphere. The organic acid responsible for Al3+ stress response varies from species to species, which in the case of blackgram (Vigna mungo L.) is citrate. In blackgram, an Arabidopsis malate transporter, AtALMT1, was overexpressed with the motive of inducing enhanced exudation of malate. Transgenics were generated using cotyledon node explants through Agrobacterium tumefaciens-mediated transformation. The putative transgenics were initially screened by AtALMT1-specific genomic DNA PCR, followed by quantitative PCR. Two independent transgenic events were identified and functionally characterized in the T3 generation. The transgenic lines, Line 1 and 2, showed better root growth, relative water content and chlorophyll content under Al3+ stress. Both lines also accounted for less oxidative damage, due to reduced accumulation of ROS molecules. Photosynthetic efficiency, as measured in terms of Fv /Fm , NPQ and Y(II), increased when compared to the wild type (WT). Relative expression of genes (VmSTOP1, VmALS3, VmMATE) responsible for Al3+ stress response in blackgram showed that overexpression of a malate transporter did not have any effect on their expression. Malate exudation increased whereas citrate exudation did not show any divergence from the WT. A pot stress assay found that the transgenics showed better adaptation to acidic soil. This report demonstrates that the overexpression of a malate transporter in a non-malate exuding species improves adaptation to Al3+ toxicity in acidic soil without effecting its stress response mechanism.

Association of Low Level of High Density Lipoprotein cholesterol with Acute Coronary syndrome.

Incidence of coronary artery disease (CAD) is increasing in developing countries in Bangladesh with improvement of socioeconomic status, urbanization, changes of dietary habits and lifestyle. Dyslipidaemia is one of the major contributors increase CAD risk. This study was aimed to find out the association of low level HDL-C with acute coronary syndrome. This cross sectional study was conducted in the department of cardiology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from August 2009 to May 2010. Sociodemographic characteristics, smoking, hypertension, FBS, serum total cholesterol level, HDL-C, LDL-C, Triglyceride level were important variable considered. A total number of 100 respondents consisted of 50 cases (patient) Group I and 50 healthy people (control) Group II. Investigations included ECG, Troponin-I, FBS and Fasting Lipid Profile. The data was analyzed by computer with the help of SPSS. Chi-square test, T-test, ANOVA test used as test of significance. The mean level in cases of HDL-C 39.3±5.1 and in control level HDL-C 34.2±3.4 statistically significant (p<0.0001). In both group low concentration HDL-C (<40mg/dl) risk for CAD. Un-adjusted odds ratio 95% CI determinants of ACS, HDL-C of OR was 0.2. So, HDL-C is not protective factor. In multivariate logistic regression analysis that adjusted for confounders of HDL-C level (age, sex, smoking, hypertension, TC, LDL-C, TG) associated with ACS. HDL-C was strong predictor of ACS (RR in the highest) compared with lowest quarantile = 0.02; (95% CI=0.003-0.173; P for trend <0.0001). The study reflected that low HDL-C level associated with ACS. Categorization of patients with ACS on the basis HDL-C level may be helpful for risk stratification and management.

Relationship between Triglyceride and HDL-C ratio with Acute Coronary Syndrome.

Cardiovascular diseases (CVD) is the leading cause of death worldwide, responsible for one third of death, coronary artery disease (CAD) is the most common cause. Dyslipidaemiais one of the major contributors increased of CAD risk. This study was aimed to find out the relationship between triglyceride and HDL cholesterol ratio with acute coronary syndrome. This cross sectional study was conducted in the department of Cardiology, Mymensingh Medical College Hospital from August 2009 to May 2010. Smoking, hypertension, serum total cholesterol level, serum HDL-C, LDL-C, triglyceride (TG) level were important variable considered. A total number of 100 respondents consisted of 50 cases (patient) and 50 healthy persons (control). Investigations included ECG, Troponin-I, FBS and lipid profile. The data was analyzed by computer with the help of SPSS; Chi-square test, 't' test, ANOVA test used as test of significance. The mean level in cases of TG 168.2±88.0 vs. HDL 41.3±5.1 in control level TG 141.2±45.3 and HDL 34.2±3.4. TG/HDL ratio cases 4.2±1.7 and control 4.1±1.3. This ratio >4 is atherogenic for CAD. Unadjusted odds ratio TG/HDL ratio level high (>1). In multivariable regression analysis, TG/HDL ratio was strong relation with ACS. The study reflected that high TG/HDL ratio is associated with ACS. Categorization of patient with ACS on the basis of high TG/HDL ratio will be helpful for risk stratification and management.

An IL-10 dominant polarization of monocytes is a feature of Indian Visceral Leishmaniasis.

Leishmania donovani, the causative parasite of Visceral Leishmaniasis (VL), deviously manipulates host monocytes/macrophages to ensure its survival. Although monocytes/macrophages from patients with VL have demonstrated an impaired oxidative burst and antigen presentation, an unanswered yet pertinent question remains as to whether they are deactivated or alternatively activated. The significantly raised plasma levels of IL-4/IL-13 and IL-10 in VL patients suggested a microenvironment conducive for alternative activation of monocytes/macrophages. Accordingly, the classical markers for IL-4-driven monocytes/macrophages [M(IL-4)] were studied namely intramonocytic CD206+ , circulating CCL22 and CCL17, and were unchanged. Furthermore, the mRNA expression of Kruppel-like factor 4 (KLF4), peroxisome proliferator-activated receptors (PPAR)-γ and arginase-I (ARG-I) in peripheral blood mononuclear cells was unaltered. However, markers for IL-10-driven monocytes/macrophages [M(IL-10)], namely soluble CD163, intramonocytic IL-10, and circulating CXCL13 were significantly increased. Monocytes/macrophages of patients with VL demonstrated an increased expression of markers for M(IL-10), along with the absence of markers for M(IL-4). Taken together, in human VL, manipulation of these IL-10 polarized monocytes-macrophages may pave the way for improved therapeutic outcomes.

Forgotten, Encrusted Ureteral Stents: Removal - Multimodal Endourologic Approach.

Ureteral stent placement is a common procedure in urologic practice. Forgotten, encrusted D/J stents represent a difficult problem for urologists. The major complications are infection, impaired renal function, migration, encrustation, stone formation and multiple fragmentation of stent. A consensus on the best therapeutic approach is still lacking. Here we present our experience with endoscopic management of this challenging problem and discuss the multimodal endourologic approaches for treating forgotten, encrusted ureteral stents. In this prospective observational study 29 patients (17 males and 12 females), age ranges from 19 to 57 years with 35 (23 unilateral and 6 bilateral) encrusted ureteral stents, indwelling for 5 to 78 months were treated in the Department of Urology, Dhaka Medical College Hospital (DMCH), Dhaka, Bangladesh from January 2011 to December 2015. All patients were evaluated by urine culture and sensitivity, renal function. Stent encrustation and the associated stone burden were estimated by plain radiograph. Treatment decisions were made based on the clinical presentation, degree of encrustation, stone burden and image findings. Patients were followed up to 06 months. The main indications for stenting were pyelolithotomy, ureterolithotomy, ureteroneocystostomy, URS and pyeloplasty. In kidney, mild encrustation was common (48.3%) moderate encrustation (27.6%) was less common; where as in ureter and urinary bladder, moderate encrustation was common (72.4% and 44.8%). Over three-quarters 22(75.9%) of the patients underwent extracorporeal shockwave lithotripsy (ESWL) and 10(34.5%) percuteneousnephrostomy preoperatively. Retrograde ureteroscopy with intracorporeal lithotripsy (URS & ICPL) was done in 29 cases and cystolitholapaxy (CLL) in 16(55%) cases. Cystolithotomy & PCNL was rarely done. The mean number of procedures was 2.8 (range: 1-7). Using these multimodal approaches, all stents and associated stones were eventually removed with minor complications. Nine patients developed haematuria, 5 urosepsis and 4 both haematuria & urosepsis. Multimodal endourologic approaches can safely remove forgotten, encrusted D/J stents, if treatment is tailored to the volume of encrustation and associated stone. Imaging evaluation and documentation of negative urine culture are imperative prior to any attempt to remove the stent.

trans-4,4'-Dihydroxystilbene (DHS) protects PC12 cells from oxidative damage but induces reactive oxygen species-mediated apoptosis in SHSY-5Y cell line.

Polyphenols can exert both, antioxidant and pro-oxidant properties, depending on cell types as well as their concentrations. Hence, it was of interest to examine if the naturally occurring resveratrol analog, trans-4,4'-dihydroxystilbene (DHS) also exert both these activities in a biphasic or cell-specific manner. In this study, we established the cytoprotective action of DHS against hydrogen peroxide (H2O2)-induced apoptotic death of the PC12 cells. DHS reduced mitochondrial membrane permeabilization and deactivated reactive oxygen species (ROS)-mediated caspase-3 activation in the H2O2-treated PC12 cells. However, it induced apoptosis in the human neuroblastoma SHSY-5Y cell line by destabilizing mitochondrial membrane, augmenting ROS and activating caspapse-3. DHS showed better activity than resveratrol in both the chosen models.

PKCλ/ι signaling promotes triple-negative breast cancer growth and metastasis.

Triple-negative breast cancer (TNBC) is a distinct breast cancer subtype defined by the absence of estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2/neu), and the patients with TNBC are often diagnosed with higher rates of recurrence and metastasis. Because of the absence of ER, PR and HER2/neu expressions, TNBC patients are insensitive to HER2-directed and endocrine therapies available for breast cancer treatment. Here, we report that expression of atypical protein kinase C isoform, PKCλ/ι, significantly increased and activated in all invasive breast cancer (invasive ductal carcinoma or IDC) subtypes including the TNBC subtype. Because of the lack of targeted therapies for TNBC, we choose to study PKCλ/ι signaling as a potential therapeutic target for TNBC. Our observations indicated that PKCλ/ι signaling is highly active during breast cancer invasive progression, and metastatic breast cancers, the advanced stages of breast cancer disease that developed more frequently in TNBC patients, are also characterized with high levels of PKCλ/ι expression and activation. Functional analysis in experimental mouse models revealed that depletion of PKCλ/ι significantly reduces TNBC growth as well as lung metastatic colonization. Furthermore, we have identified a PKCλ/ι-regulated gene signature consisting of 110 genes, which are significantly associated with indolent to invasive progression of human breast cancer and poor prognosis. Mechanistically, cytokines such as TGFß and IL1ß could activate PKCλ/ι signaling in TNBC cells and depletion of PKCλ/ι impairs NF-κB p65 (RelA) nuclear localization. We observed that cytokine-PKCλ/ι-RelA signaling axis, at least in part, involved in modulating gene expression to regulate invasion of TNBC cells. Overall, our results indicate that induction and activation of PKCλ/ι promote TNBC growth, invasion and metastasis. Thus, targeting PKCλ/ι signaling could be a therapeutic option for breast cancer, including the TNBC subtype.

Toll-like receptors and CD40 modulate each other's expression affecting Leishmania major infection.

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and results in innate immune system activation that results in elicitation of the adaptive immune response. One crucial modulator of the adaptive immune response is CD40. However, whether these molecules influence each other's expression and functions is not known. Therefore, we examined the effects of TLRs on CD40 expression on macrophages, the host cell for the protozoan parasite Leishmania major. While polyinosinic-polycytidylic acid [poly (I:C)], a TLR-3 ligand, lipopolysaccharide (LPS), a TLR-4 ligand, imiquimod, a TLR-7/8 ligand and cytosine-phosphate-guanosine (CpG), a TLR-9 ligand, were shown to enhance CD40 expression, CD40 stimulation enhanced only TLR-9 expression. Therefore, we tested the synergism between CD40 and CpG in anti-leishmanial immune response. In Leishmania-infected macrophages, CpG was found to reduce CD40-induced extracellular stress-regulated kinase (ERK)1/2 activation; with the exception of interleukin (IL)-10, these ligands had differential effects on CD40-induced IL-1α, IL-6 and IL-12 production. CpG significantly enhanced the anti-leishmanial function of CD40 with differential effects on IL-4, IL-10 and interferon (IFN)-γ production in susceptible BALB/c mice. Thus, we report the first systematic study on CD40-TLR cross-talk that regulated the experimental L. major infection.

Keratometric astigmatism evaluation after trabeculectomy.

INTRODUCTION: Post-operative astigmatism is one of the most important causes for diminution of vision after trabeculectomy. OBJECTIVE: To evaluate the induced corneal astigmatism following trabeculectomy with the use of 8-0 silk suture. MATERIALS AND METHODS: A prospective interventional study was done including 100 consecutive eyes of 84 patients who underwent trabeculectomy with the use of 8-0 silk suture. The postoperative induced astigmatism on the 1st post-operative day, 3rd week and after 6 months was determined. STATISTICS: Vector analysis was performed on the data using a computerized method for calculating the surgically induced astigmatism (SIA) for each eye at every time point postoperatively. In order to analyze group changes, we also performed vector decomposition which gave us a mathematical expression of the changes in astigmatism "with the rule" (WTR) or "against the rule" (ATR). RESULTS: The mean age of all the patients was 53.31 11.39 years. The mean 1st post-operative surgically induced astigmatism (SIA) was 2.73 D ( 99 degree ) which reduced to 0.41 D ( 58 degree) at the 3rd week and 0.43 ( 21 degree) at 6 months. The mean WTR astigmatism was 4.46 D and ART astigmatism was 1.42 D on the 1st post-operative day which was significantly high ( p less than 0.0001). At the 3rd week and 6 months WTR astigmatism ( 1.40 D and 1.08D ) and ATR astigmatism (1.27 D and 1.10 D) showed no significant changes (p=0.69,0.97 respectively. CONCLUSION: Trabeculectomy with the use of 8/0 silk sutures showed significantly high 1st post-operative day SIA which nevertheless perished fast to a minimum amount at just 3 weeks.

Leishmania expressed lipophosphoglycan interacts with Toll-like receptor (TLR)-2 to decrease TLR-9 expression and reduce anti-leishmanial responses.

Two different Toll-like receptors (TLRs) have been shown to play a role in host responses to Leishmania infection. TLR-2 is involved in parasite survival in macrophages upon activation by lipophosphoglycan (LPG), a virulence factor expressed by Leishmania. In contrast, activation of TLR-9 has been shown to promote a host-protective response. However, whether there is a relationship between the interaction of LPG and TLR-2, on one hand, with the effect of TLR-9, on the other hand, remains unknown. In this study, we report that in-vitro infection of macrophages with a L. major parasite with high expression levels of LPG results in decreased TLR-9 expression compared to infection with a L. major parasite with lower expression levels of LPG. Addition of anti-LPG as well as anti-TLR-2 antibodies prevents this reduction of TLR-9 expression. Also, the addition of purified LPG to macrophages results in a decrease of TLR-9 expression, which is shown to be mediated by transforming growth factor (TGF)-ß and interleukin (IL)-10. Finally, in-vitro treatment of macrophages with anti-LPG and/or anti-TLR-2 antibodies before infection reduces the number of amastigotes in macrophages and co-treatment of mice with anti-TLR-2 antibodies and cytosine-phosphate-guanosine (CpG) reduces footpad swelling and parasite load in the draining lymph nodes, accompanied by an interferon (IFN)-γ-predominant T cell response. Thus, for the first time, we show how interactions between LPG and TLR-2 reduce anti-leishmanial responses via cytokine-mediated decrease of TLR-9 expression.

Stiffness tomography exploration of living and fixed macrophages.

Stiffness tomography is a new atomic force microscopy imaging technique that allows highlighting structures located underneath the surface of the sample. In this imaging mode, such structures are identified by investigating their mechanical properties. We present here, for the first time, a description of the use of this technique to acquire detailed stiffness maps of fixed and living macrophages. Indeed, the mechanical properties of several macrophages were studied through stiffness tomography imaging, allowing some insight of the structures lying below the cell's surface. Through these investigations, we were able to evidence the presence and properties of stiff column-like features located underneath the cell membrane. To our knowledge, this is the first evidence of the presence, underneath the cell membrane, of such stiff features, which are in dimension and form compatible with phagosomes. Moreover, by exposing the cells to cytochalasin, we were able to study the induced modifications, obtaining an indication of the location and mechanical properties of the actin cytoskeleton.

Restoration of tumor suppressor p53 by differentially regulating pro- and anti-p53 networks in HPV-18-infected cervical cancer cells.

Abrogation of functional p53 is responsible for malignant cell transformation and maintenance of human papilloma virus (HPV)-infected cancer cells. Restoration of p53 has, therefore, been regarded as an important strategy for molecular intervention of HPV-associated malignancies. Here we report that differential regulation of pro- and anti-p53 setups not only upregulates p53 transcription but also stabilizes and activates p53 protein to ensure p53-induced apoptosis in HPV-18-infected cervical cancer. Functional restoration of p53 can be achieved by non-steroidal anti-inflammatory drug celecoxib via multiple molecular mechanisms: (i) inhibition of p53 degradation by suppressing viral oncoprotein E6 expression, (ii) promoting p53 transcription by downmodulating cycloxygenase-2 (Cox-2) and simultaneously retrieving p53 from Cox-2 association and (iii) activation of p53 via ataxia telangiectasia mutated-/p38 mitogen-activated protein kinase-mediated phosphorylations at serine-15/-46 residues. That restored p53 is functional has been confirmed by its ability of transactivating Bax and p53-upregulated modulator of apoptosis, which in turn switch on the apoptotic machinery in these cells. Studies undertaken in biopsy samples of cervical carcinoma further validated celecoxib effect. Our approaches involving gene manipulation and pharmacological interference finally highlight that celecoxib alters pro- and anti-p53 networks, not in isolation but in concert, to rejuvenate p53-dependent apoptotic program in HPV-infected cervical cancer cells.