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Fluoride contamination in groundwater may pose serious health issues. Among all the technologies, adsorption is considered to be highly efficient and is widely used for remediation in environment. In the present study, copper oxide nanoparticles (CuO) were synthesized by chemical precipitation method and used as adsorbent. The study intends to examine copper oxide nanoparticles behaviour when fluoride ions are present in an aqueous solution. The batch mode experiment demonstrated a substantial ability of the copper oxide nanoparticles for adsorption of fluoride with an adsorption capacity of 69.9 mg/g at a pH of 6, temp 298 K and adsorbent dose of 0.5 g/L. [ABSTRACT FROM AUTHOR]

Mathematical models are becoming indispensable tools to explore the complexities of biological systems at cellular levels. We present a model to explore the baseline immune cell interactions for in vitro polyclonal antibody synthesis via B-cells regulated by helper and regulatory T-cells. The model incorporates interactions of antigen-presenting cells, T-cells, regulatory T-cells, and B-cells with each other and predicts time-dependent trajectories of these cells and antibody synthesis stimulated by pokeweed mitogen. We used an ordinary differential equation-based approach to simulate the dynamic changes in the cells and cytokines numbers due to the cellular and humoral response to pokeweed mitogen stimulation. The parameters of the ordinary differential equations model are determined to yield a normal immune response as observed in the pokeweed mitogen-stimulated in vitro antibody synthesis via normal T, B, and antigen-presenting cells. The dose effects of antigen load and basal values of regulatory T-cells on the profiles of various immune response variables are also evaluated. [ABSTRACT FROM AUTHOR]

[Display omitted] • 13C NMR chemical shifts are very important in identifying the chemical surroundings of carbon nuclei in a molecule. • The electronic and steric environment of the ligand has a significant impact on the chemical shift of the carbonyl carbon (C O) in the carboxylate ligand. • The type of the ligand and the degree of its interaction with the tin atom may be determined from the chemical shift of the carbonyl carbon in a carboxylate ligand. • The intensity of the connection between the tin atom and the carboxylate ligand may be determined for butyltin carboxylates by measuring the coupling constant between the carbonyl carbon and the nearby carbon atoms in the ligand. This review article describes the findings of research on the 13C NMR spectra of di- and tri-butyltin carboxylates. The purpose of this review is to shed light on the experimental values of 13C NMR chemical shifts, as well as their importance in identifying the chemical surroundings of carbon nuclei. The study aims to gain a deeper understanding of how carbon nuclei interact with their electronic surroundings and how substituents attached can influence these interactions. The information presented in this review highlights the crucial role played by 13C NMR chemical shifts in establishing the structure of carbon frameworks, making it an indispensable tool for the structure elucidation. [ABSTRACT FROM AUTHOR]

Adoptive transfer of Bispecific antibody Armed activated T cells (BATs) showed promising anti-tumor activity in clinical trials in solid tumors. The cytotoxic activity of BATs occurs upon engagement with tumor cells via the bispecific antibody (BiAb) bridge, which stimulates BATs to release cytotoxic molecules, cytokines, chemokines, and other signaling molecules extracellularly. We hypothesized that the release of BATs Induced Tumor-Targeting Effectors (TITE) by this complex interaction of T cells, bispecific antibody, and tumor cells may serve as a potent anti-tumor and immune-activating immunotherapeutic approach. In a 3D tumorsphere model, TITE showed potent cytotoxic activity against multiple breast cancer cell lines compared to control conditioned media (CM): Tumor-CM (T-CM), BATs-CM (B-CM), BiAb Armed PBMC-CM (BAP-CM) or PBMC-CM (P-CM). Multiplex cytokine analysis showed high levels of Th1 cytokines and chemokines; phospho-protein signaling array data suggest that the prominent JAK1/STAT1 pathway may be responsible for the induction and release of Th1 cytokines/chemokines in TITE. In xenograft breast cancer models, IV injections of 10× concentrated TITE (3×/week for 3 weeks; 150 μl TITE/injection) was able to inhibit tumor growth significantly (ICR/scid, p < 0.003; NSG p < 0.008) compared to the control mice. We tested the key components of the TITE for immune activating and anti-tumor activity individually and in combinations, the combination of IFN-γ, TNF-α and MIP-1β recapitulates the key activities of the TITE. In summary, master mix of active components of BATs–Tumor complex-derived TITE can provide a clinically controllable cell-free platform to target various tumor types regardless of the heterogeneous nature of the tumor cells and mutational tumor. [ABSTRACT FROM AUTHOR]

In this study, we investigated the ability of bispecific antibody armed activated T cells to target drug resistant pancreatic cancer cells and whether or not "priming" these resistant cancer cells with bispecific antibody armed activated T cells could enhance subsequent responsiveness to chemotherapeutic drugs. Chemotherapeutic responses for pancreatic cancer are either limited or the tumors develop resistance to chemotherapy regimens. The impetus for this study was the remarkable clinical response seen in our earlier phase I/II clinical trial: a pancreatic cancer patient with drug resistant tumors who showed progression of disease following three infusions of anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (EGFR BATs) was restarted on the initial low dose of 5-fluorouracil showed complete response, suggesting that BATs infusions may have sensitized patient's tumor for chemoresponsiveness. In the current study, we tested the hypothesis that BATs can sensitize tumors for chemoresponsiveness. Gemcitabine or cisplatin-resistant MiaPaCa-2 and L3.6 cell lines were effectively targeted by EGFR BATs. Priming of drug sensitive or resistant cells with EGFR BATs followed by retargeting with lower concentrations of 50% inhibitory concentration of gemcitabine or cisplatin showed enhanced cytotoxicity. Gemcitabine or cisplatin-resistant cell lines show an increased proportion of CD44+/CD24+/EpCAM+ cancer stem like cells as well as an increased number of ABC transporter ABCG2 positive cells compared to the parental cell lines. These data suggest that bispecific antibody armed activated T cells can target and kill chemo-resistant tumor cells and also markedly augment subsequent chemotherapeutic responsiveness, possibly by modulating the expression of ABC transporters. [ABSTRACT FROM AUTHOR]

Purpose: Although adoptive cell therapy with chimeric antigen receptor (CAR)-engineered T cells has shown durable clinical efficacy in patients with CD19+ B cell malignancies, the application of this approach to solid tumors is challenging. The goal of this proof-of-concept study was to investigate whether loading of CD19-CAR T cells (CART19) with anti-HER2 or anti-EGFR bispecific antibodies (BiAb) will target HER2+/EGFR+ CD19− targets and signal the intracellular domain of CAR without engaging antigen-specific CD19 ScFv of CAR T cells. Methods: We used CART19 armed with anti-CD3 (OKT3) × anti-HER2 BiAb (HER2Bi) or anti-CD3 (OKT3) × anti-EGFR BiAb (EGFRBi) to evaluate the cytotoxicity directed at HER2 or EGFR expressing cancer cell lines compared with unarmed CART19 measured by short-term 51Cr release assay and long-term real-time cell analysis using xCelligence. We also determined the differences in exhaustion or effector phenotypes and cytokine profiles during the short- and long-term cytotoxicity assays. Results: Specific cytotoxicity was exhibited by CART19 armed with HER2Bi or EGFRBi against multiple tumor cell lines. Armed CART19 and armed activated T cells (ATC) showed comparable specific cytotoxicity that ranged between 10 and 90% against breast, pancreatic, ovarian, prostate, and lung cancer cell lines at 10:1 E/T ratio. Serial killing (repeated killing) by HER2Bi-armed CART19 ranged between 80 and 100% at 10:1 E/T ratio against MCF-7 cells up to 19 days (up to 4th round of repeated killing) measured by a real-time cell analysis without CART19 becoming exhausted. Conclusions: HER2Bi- or EGFRBi-armed CART19 exhibited specific cytotoxicity against multiple HER2+/EGFR+/CD19− tumor targets in overnight and long-term serial killing assays. CART19 showed improved survival and were resistant to exhaustion after prolonged repeated exposure to tumor cells. [ABSTRACT FROM AUTHOR]

The new titanocene dichloride complexes of composition [Cp2Ti(L)(LI-V)] Cl (where HL = 1-adamantylamine, LI-V = Tryptophol, 5-Methoxyindole, Indole-5-Carboxaldehyde, 5-Cyanoindole, 6-Nitroindole respectively) were synthesized and characterized using elemental analysis and different spectroscopic techniques. The synthesized complexes were evaluated for their binding efficacy with calf-thymus DNA (ct-DNA). Complexes (1, 3 and 4) bind to ct-DNA through non-intercalation mode while complexes (2, 5) exhibited intercalation binding mode. Further, complexes were investigated for their antioxidant potential using DPPH assay. Complex 2 exhibited highest antioxidant activity out of all synthesized complexes. Gel electrophoresis technique was employed to investigate the DNA cleavage ability of complexes against DNA plasmid pBR322. Gel electrophoretic results suggested that complexes 3, 4 and 5 had the ability to change the supercoiled form of DNA plasmid to open circular form. Results of antibacterial activity studies using agar well diffusion technique displayed that complex 1 exhibited more activity against E. coli and L. monocytogenes than free ligand. Complexes 2, 3 and 4 had better antibacterial activity than their respective ligands against E. coli. Antifungal activity data stated that complex 3 had more potent activity than its ligand against A. alter strain. In addition, invitro anticancer activity of ligands (LI-V) and their respective titanocene complexes was investigated using MTT assay on L6 immortalized cell line and L929 cancerous cell line. Complexes 1, 2 and 4 displayed better cytotoxicity than their ligands against L6 cell line. Complex 2 displayed better cytotoxicity than other complexes against both cell lines (L6 and L929). [ABSTRACT FROM AUTHOR]

This was a phase I/II adoptive T cell trial in 7 locally advanced and metastatic pancreatic cancer patients using 3–8 infusions of anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (BATs) to determine safety, the maximum tolerated dose (MTD), immune responses, time to progression (TTP), and overall survival (OS). Study Design: T cells obtained by apheresis were expanded and armed with EGFRBi, cryopreserved for infusions. In a phase I dose escalation, five patients received three weekly infusions of 10–40 × 109 BATs/infusion followed by a booster infusion 3 months later, and 2 patients received 8 infusions twice weekly for 4 weeks in a phase II. The trials were registered at , NCT01420874 and NCT02620865. Results: There were no dose-limiting toxicities (DLTs), and the targeted dose of 80 × 109 BATs was met. The median TTP is 7 months, and the median OS is 31 months. Two patients had stable disease for 6.5 and 25+ months, and two patients developed complete responses (CRs) after restarting chemotherapy. Infusions of BATs induced anti-pancreatic cancer cytotoxicity, innate immune responses, cytokine responses (IL-12, IP-10), and shifts in CD4 and CD8 Vβ repertoire with enhanced cytoplasmic IFN-γ staining in the Vβ repertoire of the CD8 subset that suggest specific clonal TCR responses. Conclusions: Infusions of BATs are safe, induce endogenous adaptive anti-tumor responses, and may have a potential to improve overall survival. [ABSTRACT FROM AUTHOR]

A series of novel binuclear titanium (IV) complexes, [Ti(sal)LI–V(OBu)(μ-OBu)]2, was synthesized by the reaction of salicylic acid (H2sal) and substituted indoles (LI = Tryptophol, LII = 5-Methoxyindole, LIII = Indole-5-Carboxaldehyde, LIV = 5-Cyanoindole, LV = 6-Nitroindole) with titanium(IV) tetrabutoxide in predetermined molar ratios under stirring and refluxing conditions in THF solvent. The chemical structure of synthesized complexes was found to be binuclear based on the FTIR, IH (proton) NMR and ESI-Mass (Electron-spray ionization) spectroscopic data. Each titanium metal was surrounded by two bridged butoxy groups and one terminal butoxy group along with bidentate salicylic acid and coordinated substituted indoles. These complexes were investigated for antioxidant potential using DPPH (2,2-diphenyl-1-picrylhydrazyl) assay where they exhibited moderate to good antioxidant activity. Gel electrophoresis method was employed to study the ct-DNA (calf thymus DNA) cleavage efficiency of complexes using an agarose gel. Antimicrobial results stated that most of the complexes were ineffective against selected bacterial and fungal strains. Complexes were investigated for anticancer activity against two selected cancerous cell lines (L6 and L929). From MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay, it has been inferred that complexes 1 and 2 have better anticancer properties than their respective indoles. The DNA binding study of synthesized complexes studied in order to check their efficacy to hinder DNA replication/transcription using electronic absorption and fluorescence spectroscopy revealed them as electrostatic/groove binder. The synthesized complexes were also evaluated for antidiabetic properties using alpha-amylase inhibition assay and complex 5 possessed better alpha-amylase inhibition activity than other complexes. Synopsis: The synthesis, structural characterizationand biological activities of a novel binuclear titanium(IV) complexes [Ti(sal)LI–V(OBu)(μ-OBu)]2 is reported. [ABSTRACT FROM AUTHOR]

Background: The school health program is a flagship program of Government of India with a focus on improving the physical and mental health of school children, but there is no specific strategy to screen for mental health disorders under the school health program. Also, the estimation of the prevalence of common mental disorders (CMDs) such as anxiety, depression, and psychosocial distress among school children is lacking. Methods: The author conducted a cross‑sectional study among 742 adolescent schoolgirls from one government, one government‑aided, and one private school in an urban area in Gujarat. We used the pre‑validated instrument, general health questionnaire‑12 (GHQ‑12) to screen for CMDs. We estimated adjusted odds of association between screening positive for CMDs and various determinants. Results: 48.78% adolescent girls screened positive for CMDs which is alarming. Among sociodemographic characteristics, the type of school (adjusted odds of private is 1.8 and government 1.6), mother’s higher education (3.0), father’s less education (3.1), and working mother (1.5) had shown significant association with positive cases of the girls. Among psychosocial factors, abnormal sleep patterns (1.9) and disturbance in studies (2.3) have been found statistically significant for the presence of mental health problems among adolescent girls as per the GHQ score. Conclusion: CMDs such as anxiety, depression, and psychosocial distress were indeed very common among adolescent school‑going girls in an urban area of Gujarat, India. There is an urgent need to focus attention on the mental health of adolescent girls. [ABSTRACT FROM AUTHOR]

Introduction: Unwanted or unintended pregnancy is common and in such a case access to safe abortion services is a women's right. The MTP act of 1971 has provisions which make abortion services available and accessible freely. MTP pills make first trimester abortions possible safely without having to undergo any surgical procedure. But lack of correct knowledge limits its safe use. Objectives: To study the Knowledge, Attitude and Practices related to use of medical abortion pills among married women in an urbanized village of Delhi. Materials and Methods: A cross sectional study was conducted among 224 married women in reproductive age group residing in an urbanized village of Delhi. Mixed quantitative and qualitative methodology was used in Data collection and analysis. Results: 69.2% women were under 30 years of age. 79.7% women had at-least two children and 26.4% had at least one abortion. 69.64% women knew about at least one method of abortion (Medical or Surgical). Only 38.8% women knew that abortions are legal. 61.1% had heard about abortion "pills". Of them, as many as 41% said these pills can be procured directly from the chemist. Only 5.8% had correct knowledge regarding use of these pills. Misconceptions about side effects were also common.50% said they would feel shy to discuss these pills with a male doctor. 12.5% reported using medical abortion pills, though ever having unplanned pregnancy was reported by 52.2% women. 78.57% of the women reporting MTP pill use, took the medicines directly from the chemist. Conclusion: Though the general attitude towards use of medical abortions was positive in the community, there were widespread misconceptions. There is an urgent need to increase the awareness about hazards of self-medication of medical abortion pills. [ABSTRACT FROM AUTHOR]

Background: Nutrition' is a very essential component of undergraduate teaching in MBBS curriculum. In this age of growing dietconsciousness and fitness, skill development of medical graduates in designing healthy and culturally appropriate diet is imperative. Objective: To demonstrate the effectiveness of Diet Demonstration Training technique in improving the knowledge about basic principles of nutrition in medical undergraduates. Methodology: A pilot pretest-posttest study was conducted among 16 undergraduate medical students participated in a pre-conference workshop. Steps of diet demonstration for Under-graduate students were performed and a pretest - posttest was conducted using a self designed self administered questionnaire. Results: The mean marks received by the students were 8.69 & 10.31 out of 15 in the pretest & post-test respectively (p value <0.017). Overall 56.3% & 93.6% students performed well in pre-test and post-test respectively. Conclusion: There was significant improvement in nutrition education of participated undergraduates. [ABSTRACT FROM AUTHOR]

Background: Adolescence is a critical time of formative growth and development, which is highly influenced by their peer groups and family. Behaviours they adopt during this period have strong bearing on their whole life and family. Aim: This study aims to elaborate various socio-behavioural issues among school going adolescent girls. Methods: The study was school based descriptive cross-sectional study conducted in a school of Haryana. All the girls of class 9th and 11th present during study period were studied and analysed. The study tool was self-administered semi structured questionnaire. Data was entered and analysed on Microsoft excel and SPSS 16 and appropriate test were applied according to data. Results: Total 93 girls of class 9th and 11th were enrolled during study period. Adolescent girls belonged to age group12-18 years. Out of 93 girls, 3 girls reported history of substance use, 25 girls reported no physical activity and 4 girls reported disturbed sleep. Feeling of inferiority in academics and looks was present in 15.1 % and 11.8% girls respectively. Some girls (8.6%) also reported peer pressure for smoking. Most adolescent girls shared very good or good relationship with their friends (82.8%), parents (86.0%) and teachers (83.8%). In this study, 33.3% girls reported disturbance in their studies. Conclusion: This study concludes the significant presence of serious socio-behavioural problems among school going adolescent girls, which may have detrimental effect on their current and future health. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus is one of the expensive diseases in the world. The cost of care in diabetes is high mainly because of its chronic nature and complications. Moreover, it affects economically productive section of society. But studies on economic impact of diabetes are very limited in India. The present aims to estimate the annual out of pocket expenditure of diabetic care among diabetics living in an underprivileged community of East Delhi. Methodology: A community based one year longitudinal study was conducted in Kalyanpuri area of East Delhi. All the diabetes patients (consecutive sampling) aged more than 25 years and who were the permanent residents of Kalyanpuri, attending the Diabetic Clinic of Lal Bahadur Shastri Hospital in November-December 2014were selected for the study. A pre-tested semi-structured interview schedule was used as study tool. Each subject was followed up 3 monthly from January 2015-December 2015. Both direct and indirect expenditure were estimated. Results: Total 153 study subjects were selected out of which 2 migrated and 1 died. So, data from 150 study subjects were collected and analyzed. The Mean and median annual expenditure was Rs. 8,958 ±11,704 and Rs. 4,443 respectively. The mean per capita annual direct expenditure was estimated to be Rs 6,821 ± 9,832 and mean annual indirect expenditure was Rs. 2,137 ± 5,622. Inpatient treatment and medicine are two major heads of expenditure. Conclusion: Expenditure on diabetes care among diabetes patients living in underprivileged community was considerably high despite of having well-functioning government hospital in vicinity of study area. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Menstrual cycle is the cyclical shedding of endometrium every 28±7 days in response to hormones. Dysmenorrhea is one of the commonest problems among the menstruating females. Dysmenorrhoea is defined as symptoms associated with menstruation, such as abdominal pain, cramping, backache that interfere with activities of daily living Dysmenorrhoea has been found to result in marked reduction in quality of life among females of reproductive age. AIM: The aim of study was to assess the prevalence of dysmenorrhea, to compare the severity, and to determine the impact of dysmenorrhea on Activity of Daily Living (ADLs) among married and unmarried nursing personnel. MATERIALS & METHODS: A descriptive cross-sectional study was employed. Multi-stage sampling was done to find out the subjects having dysmenorrhoea among nursing personnel under study. Socio demographic data, menstrual history of subjects, history of dysmenorrhea was documented using an interview schedule. Lawton Instrumental Activities of Daily Living scale was used to know the impact of dysmenorrhoea on activities of daily living of the study subjects. 805 nursing personnel were surveyed and 651 were found to be menstruating. 263 were found to be having dysmenorrhoea. RESULTS: The overall prevalence of dysmenorrhoea among the subjects was 40.39% (43% in married and 57% in unmarried subjects). Around half (46%) subjects (both married and unmarried) were able to do their ADL during dysmenorrhoea independently, 16% were partially dependent and 38% were totally dependent. Severe pain during dysmenorrhoea was experienced by 32.4% subjects. About half (50.2%) subjects were using pharmacological treatment. Non pharmacological management such as hot fomentation, rest, jaggery and saunth was used by 27% subjects, of which around two third were using hot fomentation. CONCLUSION: The prevalence of dysmenorrhoea is lower in married as compared to unmarried women. More than half described their dysmenorrhoea as moderate and severe. Dysmenorrhoea related symptoms have negative impact on quality of life, Activity of Daily Living and can make women depend on others for her ADLs. Dysmenorrhoea is one of cause of avoiding work, leave from duty and social isolation. [ABSTRACT FROM AUTHOR]

This phase Ib clinical trial evaluated whether pretargeting of CD20 + clonogenic myeloma precursor cells (CMPCs) with anti-CD3 × anti-CD20 bispecific antibody-armed T cells (BATs) before autologous stem cell transplantation (SCT) in patients with standard-risk and high-risk multiple myeloma would induce antimyeloma immunity that could be detected and boosted after SCT. All 12 patients enrolled in this study received 2 BATs infusions before SCT, and 4 patients received a booster infusion of BATs after SCT. Pretargeting CD138 − /CD20 + CMPCs with BATs before SCT was safe and reduced levels of CMPCs by up to 58% in the postinfusion bone marrow in patients who remained in remission. Four of 5 patients who remained in remission had a >5-fold increase in IFN-γ enzyme-linked immunospot responses. SOX2 antibody increased after BATs infusions and persisted after SCT. The median anti-SOX2 level at 3 months after SCT was 28.1 ng/mL (range, 4.6 to 256 ng/mL) in patients who relapsed and 46 ng/mL (range, 28.3 to 73.3 ng/mL) in patients who remained in remission. The immune correlates suggest that infusions of targeted T cells given before SCT were able to reduce CMPC levels and induced cellular and humoral antimyeloma immunity that could be transferred and boosted after SCT. [ABSTRACT FROM AUTHOR]

Introduction: Staphylococcus aureus is a major cause of infection, and methicillin-resistant strains are increasingly being reported worldwide. This study was carried out to evaluate the antibiotic susceptibility pattern of methicillin-resistant strains of S. aureus, isolated from clinical specimens from a super specialty hospital in Delhi. Materials and Methods: The study comprised of 80 strains of S. aureus isolated from various clinical specimens. From these isolates, methicillin-resistant strains were screened, and their susceptibility pattern to vancomycin, teicoplanin, daptomycin, and linezolid was detected using standard microbiological techniques. Results: Of the 80 strains, 53 strains were found to be methicillin resistant while the rest of the 27 strains were methicillin-susceptible. Four among the 53 strains were linezolid resistant, and eight were vancomycin-intermediate. Of the 8 strains, two were teicoplanin intermediate, and one was teicoplanin resistant. All the 53 strains were sensitive to daptomycin. Conclusion: In the current study, daptomycin was found to be the only drug to which all the isolates were susceptible. However, daptomycin resistance has also been reported from elsewhere. Therefore, all the recommended measures to control the emergence and spread of these strains must be followed strictly in all health-care systems. [ABSTRACT FROM AUTHOR]

Background. New nontoxic targeted approaches are needed for patients with castrate resistant prostate cancer (CRPC). Our preclinical studies show that activated T cells (ATC) armed with anti-CD3 x anti-Her2 bispecific antibody (Her2Bi) kill prostate cancer cells lines, induce a Th1 cytokine pattern upon engagement of tumor cells, prevent the development of prostate tumors, and retard tumor growth in immunodeficient mice. These studies provided strong rationale for our phase I dose-escalation pilot study to test ATC armed with Her2Bi (aATC) for safety in men with CRPC. Methods. Seven of 8 men with CRPC were evaluable after receiving two infusions per week for 4 weeks. The men received 2.5, 5 or 10 × 109 aATC per infusion with low dose interleukin-2 and granulocyte-macrophage colony stimulating factor. Results. There were no dose limiting toxicities, and there was 1 partial responder and 3 of 7 patients had significant decreases in their PSA levels and pain scores. Immune evaluations of peripheral blood mononuclear cells in 2 patients before and after immunotherapy showed increases in IFN-γ EliSpot responses and Th1 serum cytokines. Conclusions. These results provide a strong rationale for developing phase II trials to determine whether aATC are effective for treating CRPC. [ABSTRACT FROM AUTHOR]

Adult Hookworms usually live in the duodenum and jejunum and can be recovered endoscopically for the diagnosis of chronic anaemia. This report describes an interesting case where adult hookworm (Ancylostoma duodenale) was recovered from the terminal ileum by colonoscopy in an old female patient suffering from chronic severe anemia. Her upper gastro intestinal endoscopic findings were normal and fecal occult blood test was positive. The colonoscopic finding was further confirmed by the presence of characteristic eggs of hookworm in stool microscopy and she was treated with anthelminthic along with symptomatic measures. Her clinical condition as well as the blood profile showed much improvement after treatment. Thus, colonoscopy should be considered for the presence of hookworms if the upper endoscopic findings are normal in a clinically suspected patient. [ABSTRACT FROM AUTHOR]

Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies. [ABSTRACT FROM AUTHOR]

Abstract: A phase I trial of infusing anti-CD3 × anti-CD20 bispecific antibody (CD20Bi) armed activated T cells (aATC) was conducted in high-risk/refractory non-Hodgkin''s lymphoma patients to determine whether aATC infusions are safe, affect immune recovery, and induce an antilymphoma effect. Ex vivo expanded ATC from 12 patients were armed with anti-CD20 bispecific antibody, cryopreserved, and infused after autologous stem cell transplantation (SCT). Patients underwent SCT after high-dose chemotherapy, and aATC infusions were started on day +4. The patients received 1 infusion of aATC per week for 4 weeks after SCT with doses of 5, 10, 15, and 20 × 109. aATC infusions were safe and did not impair engraftment. The major side effects were chills, fever, hypotension, and fatigue. The mean number of IFN-γ Enzyme-linked Immunosorbent Spots (ElSpots) directed at CD20 positive lymphoma cells (DAUDI, P = .0098) and natural killer cell targets (K562, P < .0051) and the mean specific cytotoxicity directed at DAUDI (P = .037) and K562 (P = .002) from pre-SCT to post-SCT were significantly higher. The increase in IFN-γ EliSpots from pre-SCT to post-SCT in patients who received armed ATC after SCT were significantly higher than those in patients who received SCT alone (P = .02). Serum IL-7, IL-15, Macrophage inflammatory protein (MIP)-1 beta, IP-10, MIP-1α, and Monokine induced by gamma interferone increased within hours after infusion. Polyclonal and specific antibodies were near normal 3 months after SCT. aATC infusions were safe and increased innate and specific antilymphoma cell immunity without impairing antibody recovery after SCT. [Copyright &y& Elsevier]

Background: Since most glioblastomas express both wild-type EGFR and EGFRvIII as well as HER2/neu, they are excellent targets for activated T cells (ATC) armed with bispecific antibodies (BiAbs) that target EGFR and HER2. Methods: ATC were generated from PBMC activated for 14 days with anti-CD3 monoclonal antibody in the presence of interleukin-2 and armed with chemically heteroconjugated anti-CD3×anti-HER2/neu (HER2Bi) and/or anti-CD3×anti-EGFR (EGFRBi). HER2Bi- and/or EGFRBi-armed ATC were examined for in vitro cytotoxicity using MTT and 51Cr-release assays against malignant glioma lines (U87MG, U118MG, and U251MG) and primary glioblastoma lines. Results: EGFRBi-armed ATC killed up to 85% of U87, U118, and U251 targets at effector:target ratios (E:T) ranging from 1:1 to 25:1. Engagement of tumor by EGFRBi-armed ATC induced Th1 and Th2 cytokine secretion by armed ATC. HER2Bi-armed ATC exhibited comparable cytotoxicity against U118 and U251, but did not kill HER2-negative U87 cells. HER2Bi- or EGFRBi-armed ATC exhibited 50—80% cytotoxicity against four primary glioblastoma lines as well as a temozolomide (TMZ)-resistant variant of U251. Both CD133- and CD133+ subpopulations were killed by armed ATC. Targeting both HER2Bi and EGFRBi simultaneously showed enhanced efficacy than arming with a single BiAb. Armed ATC maintained effectiveness after irradiation and in the presence of TMZ at a therapeutic concentration and were capable of killing multiple targets. Conclusion: High-grade gliomas are suitable for specific targeting by armed ATC. These data, together with additional animal studies, may provide the preclinical support for the use of armed ATC as a valuable addition to current treatment regimens. [ABSTRACT FROM AUTHOR]

Th17 cells, a recently discovered inflammatory T cell subtype, have been implicated with autoimmune disorders. However, mechanism of generation or functions of intratumoral Th17 cells are still unclear. We have been investigating the mechanism of induction and role of Th17 cells in malignant gliomas using primary tumor as well as cell lines. We report here that: (1) a higher frequency of Th17 cells in gliomas were associated with higher number of myeloid (CD11b) cells as well as the expression of TGF-β1 or IL-6; (2) conditioned medium from glioma cells (Gl CM) induced Th17 cell differentiation, which was inhibited by anti-TGF-β1 and anti-IL-6; (3) glioma-associated monocytes secreted Th17-promoting cytokines IL-1β and IL-23; (4) CM from glioma and monocyte co-culture (Gl+Mo CM) induced high frequency of Th17 cells in naïve T cell culture, which was abrogated by anti-IL-1β and anti-IL-23 antibodies; (5) In vitro Gl+Mo CM-mediated Th17 generation was associated with a decrease in IFN-γ and a concomitant increase in IL-10 secretion. Anti-TGF-β1, but not anti-IL-6, significantly reversed this cytokine profile. These results demonstrate prevalence of Th17 cells in gliomas and implicate the cytokines derived from the tumor as well as infiltrating myeloid cells in the induction of Th17 cells in glioma microenvironment. Moreover, the data also suggest that glioma-associated Th17 cells may contribute to immune-suppression via TGF-β1-induced IL-10 secretion. Further studies on the mechanism of tumor-infiltration, developmental pathways, and pro-/anti-tumor functions of Th17 cells will provide rationale for developing novel adjuvant immunotherapeutic strategies for malignant gliomas. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a deadly disease and has the worst prognosis among almost all cancers and is in dire need of new and improved therapeutic strategies. Conditioning of tumor cells with chemotherapeutic drug has been shown to enhance the anti-tumor effects of cancer vaccines and adoptive cell therapy. In this study, we investigated the immunomodulatory effects of pan-Bcl-2 inhibitor AT-101 on pancreatic cancer (PC) cell cytotoxicity by activated T cells (ATC). The effects of AT- 101 on cytotoxicity, early apoptosis, and Granzyme B (GrzB) and IFN-γ signaling pathways were evaluated during EGFR bispecific antibody armed ATC (aATC)-mediated killing of L3.6pl and MiaPaCa-2 PC cells pre-sensitized with AT-101. We found that pretreatment of tumor cells with AT-101 enhanced susceptibility of L3.6pl and MiaPaCa-2 tumor cells to ATC and aATC-mediated cytotoxicity, which was in part mediated via enhanced release of cytolytic granule GrzB from ATC and aATC. AT-101-sensitized L3.6pl cells showed up-regulation of IFN-γ-mediated induction in the phosphorylation of Ser 727 -Stat1 (pS727 -Stat1), and IFN-γ induced dephosphorylation of phospho-Tyr 705 -Stat3 (pY705 -Stat3). Priming (conditioning) of PC cells with AT-101 can significantly enhance the anti-tumor activity of EGFRBi armed ATC through increased IFN-γ induced activation of pS727 -Stat1 and inhibition of pY705 -Stat3 phosphorylation, and resulting in increased ratio of pro-apoptotic to anti-apoptotic proteins. Our results verify enhanced cytotoxicity after a novel chemotherapy conditioning strategy against PC that warrants further in vivo and clinical investigations. [ABSTRACT FROM AUTHOR]

Background- Antenatal depression is affecting 10% pregnant women worldwide with higher prevalence in developing countries. This causes poor maternal and foetal outcome and also affects cognitive development of the child. Aim and objective: To estimate magnitude of antenatal depression and its risk factors. Methodology- A cross-sectional survey was done at the antenatal clinic of community health department catering to an urban resettlement colony, East Delhi. Estimated sample size was 216 (including 10% non-response rate). Pregnant women attending the ANC clinic from October 2019 to February 2020 were enrolled. EPDS questionnaire was used to assess depression during pregnancy. Results-The antenatal depression was found in 11.8% subjects as per EPDS score. Working female and belonging to Muslim religion, past history of abortion, complications in previous pregnancy, financial debt, physical violence and substance use in family showed significant association with antenatal depression. Conclusion --Depression was prevalent among antenatal women and was found to be associated with various risk factors. [ABSTRACT FROM AUTHOR]

In this study, we investigated whether activated T cells (ATC) armed with bispecific antibodies (aATC) can inhibits tumor growth and MDSC development in a Th cytokine-enriched (IL-2 and IFN-γ) microenvironment. Cytotoxicity mediated by aATC was significantly higher ( P < 0.001) against breast cancer cell lines in the presence of Th cytokines as compared with control co-cultures. In the presence of aATC, CD33/CD11b/CD14/HLA-DR MDSC population was reduced significantly under both control ( P < 0.03) and Th-enriched ( P < 0.036) culture conditions. Cytokine analysis in the culture supernatants showed high levels of MDSC suppressive chemokines CXCL9 and CXCL10 in Th-enriched culture supernatants with highly significant increase ( P < 0.001) in the presence of aATC. Interestingly, MDSC recovered from co-cultures without aATC showed potent ability to suppress activated T-cell-mediated cytotoxicity ( P < 0.001), IFN-γ production ( P < 0.01) and T-cell proliferation ( P < 0.05) compared to those recovered from aATC-containing co-cultures. These data suggest that aATC can mediate enhanced killing of tumor cells and may suppress MDSC and T differentiation, and presence of Th cytokines potentiates aATC-induced suppression of MDSC, suggesting that Th-enriching immunotherapy may be beneficial in cancer treatment. [ABSTRACT FROM AUTHOR]

Abstract: Over decades, cancer treatment has been mainly focused on targeting cancer cells and not much attention to host tumor microenvironment. Recent advances suggest that the tumor microenvironment requires in-depth investigation for understanding the interactions between tumor cell biology and immunobiology in order to optimize therapeutic approaches. Tumor microenvironment consists of cancer cells and tumor associated reactive fibroblasts, infiltrating non-cancer cells, secreted soluble factors or molecules, and non-cellular support materials. Tumor associated host immune cells such as Th1, Th2, Th17, regulatory cells, dendritic cells, macrophages, and myeloid-derived suppressor cells are major components of the tumor microenvironment. Accumulating evidence suggests that these tumor associated immune cells may play important roles in cancer development and progression. However, the exact functions of these cells in the tumor microenvironment are poorly understood. In the tumor microenvironment, NF-κB plays an important role in cancer development and progression because this is a major transcription factor which regulates immune functions within the tumor microenvironment. In this review, we will focus our discussion on the immunological contribution of NF-κB in tumor associated host immune cells within the tumor microenvironment. We will also discuss the potential protective role of zinc, a well-known immune response mediator, in the regulation of these immune cells and cancer cells in the tumor microenvironment especially because zinc could be useful for conditioning the tumor microenvironment toward innovative cancer therapy. [Copyright &y& Elsevier]

Background: Myeloid-derived suppressor cells (MDSCs) are one of the major components of the immune-suppressive network, play key roles in tumor progression and limit therapeutic responses. Recently, we reported that tumor spheres formed by breast cancer cell lines were visibly smaller in a Th1 enriched microenvironment with significantly reduced differentiation of MDSC populations in 3D culture. In this study, we investigated the mechanism(s) of bispecific antibody armed ATC mediated inhibition of MDSC in the presence or absence of Th1 microenvironment. Methods: We used 3D co-culture model of peripheral blood mononuclear cells (PBMC) with pancreatic cancer cells MiaPaCa-2 [MiaE] and gemcitabine resistant MiaPaCa-GR [MiaM] cells to generate MDSC in the presence or absence of Th1 cytokines and EGFRBi armed ATC (aATC). Results: We show significantly decreased differentiation of MDSC (MiaE, p<0.005; MiaM, p<0.05) in the presence of aATC with or without Th1 cytokines. MDSC recovered from control cultures (without aATC) showed potent ability to suppress T cell functions compared to those recovered from aATC containing co-cultures. Reduced accumulation of MDSC was accompanied by significantly lower levels of COX2 (p<0.0048), PGE2 (p<0.03), and their downstream effector molecule Arginase-1 (p<0.01), and significantly higher levels of TNF-a, IL-12 and chemokines CCL3, CCL4, CCL5, CXCL9 and CXCL10 under aATC induced Th1 cytokine enriched microenvironment Conclusions: These data suggest aATC can suppress MDSC differentiation and attenuation of their suppressive activity through down regulation of COX2, PGE2 and ARG1 pathway that is potentiated in presence of Th1 cytokines, suggesting that Th1 enriching immunotherapy may be beneficial in pancreatic cancer treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: In this study, we asked whether anti-CD3-activated T cells (ATCs) from cord blood (CB) could be expanded and targeted to solid tumors or hematologic malignancies for infusions after unrelated CB stem cell transplant and whether cord blood ATCs (CBATCs) could reduce alloresponsiveness. STUDY DESIGN AND METHODS: CB mononuclear cells (MNCs) were activated with anti-CD3 (20 ng/mL) and expanded for 14 days in interleukin-2 (100 IU/mL). CBATCs were armed with anti-CD3 × anti-CD20 (CD20Bi) or anti-CD3 × anti-Her2 (Her2Bi) bispecific antibodies (CBaATCs) and tested for specific cytotoxicity, cytokine secretion, and alloresponsiveness. RESULTS: Our results show the mean expansion of CBATCs to be 37-fold after 14 days of culture from either frozen (n = 4) or fresh (n = 4) CB units. Cytotoxicity was optimal when CBATCs were armed with 50 ng of CD20Bi/106 cells. Cytotoxicity peaked between Day 8 and Day 10 for both bispecific antibodies. At an effector-to-target ratio of 25:1, the mean cytotoxicities of CBATCs armed with Her2Bi or CD20Bi were 40% (n = 4) and 30% (n = 4), respectively. CBaATCs exhibited peak specific interferon-γ enzyme-linked immunosorbent spots on Day 10. CBATCs and CBaATCs suppressed responsiveness to alloantigens by 20% to 50% when compared with normal allogeneic peripheral blood MNC response. CONCLUSION: We showed that armed CBATCs mediate specific cytotoxicity, secrete low levels of cytokines and chemokines, and demonstrate attenuated response to alloantigens. [ABSTRACT FROM AUTHOR]

In this study, we developed a unique in vitro model to mimic the endogenous tumor microenvironment to understand the effect of immunotherapy with activated T-cells (ATC) armed with anti-CD3 × anti-Her2 bispecific antibody (aATC) on antibody response by naive immune cells. This model contained a co-culture of naïve peripheral blood mononuclear cells (PBMC), breast cancer cells (SK-BR-3), ATC or aATC and CpG ODNs. Culture supernatants were tested at various time points for anti-SK-BR-3 antibodies by ELISA, Western blot and flow cytometry. PBMC cocultured with non-irradiated aATC or irradiated (*) aATC showed significant increases in anti-tumor antibody production at day 14 ( P < 0.0001) in the presence of CpG-ODN compared to unstimulated PBMC cultures ( n = 9). Antibody specificity was confirmed by ELISA, Western blot and flow cytometry. Co-cultures containing *aATC and CpG showed significantly enhanced levels of IgG ( P < 0.001) and cytokines that promote IgG synthesis including IL-13 ( P < 0.02), IFNγ ( P < 0.01) and GM-CSF ( P < 0.05) compared to unstimulated PBMC control ( n = 3). We show that aATC targeting and lysis of tumor cells induces an anti-tumor antibody response in our in vitro model. This model provides a unique opportunity to evaluate the interactions of T-cells, B-cells, and antigen-presenting cells leading to specific anti-tumor antibody responses. [ABSTRACT FROM AUTHOR]

Bispecific antibodies (BiAbs) offer a unique opportunity to redirect immune effector cells to kill cancer cells. BiAbs combine the benefits of different binding specificities of two monoclonal antibodies (mAbs) into a single construct. This unique feature of BiAbs enables approaches that are not possible with single mAbs. Advances in antibody engineering and antigen profiling of malignant cells have led to the development of a number of BiAb formats and their combinations for redirecting effector cells to tumor targets. There have been significant advances in the design and application of BiAbs for intravenous and local injection.The initial barrier of cytokine storm has been partially overcome by more recent constructs that have improved clinical effectiveness without dose-limiting toxicities. Since the recent revival of BiAbs, there has been multiple, ongoing, phase I/II and III trials, and some promising clinical outcomes have been reported in completed clinical studies. This review focuses on arming T cells with BiAbs to create the 'poor man's cytotoxic lymphocyte'. [ABSTRACT FROM AUTHOR]

Background: Pancreatic carcinoma usually is a fatal disease with no cure, mainly due to its invasion and metastasis prior to diagnosis. We analyzed the gene expression profiles of paired primary pancreatic tumors and metastatic lesions from Ela-c-myc transgenic mice in order to identify genes that may be involved in the pancreatic cancer progression. Differentially expressed selected genes were verified by semi-quantitative and quantitative RT-PCR. To further evaluate the relevance of some of the selected differentially expressed genes, we investigated their expression pattern in human pancreatic cancer cell lines with high and low metastatic potentials. Results: Data indicate that genes involved in posttranscriptional regulation were a major functional category of upregulated genes in both primary pancreatic tumors (PT) and liver metastatic lesions (LM) compared to normal pancreas (NP). In particular, differential expression for splicing factors, RNA binding/pre-mRNA processing factors and spliceosome related genes were observed, indicating that RNA processing and editing related events may play critical roles in pancreatic tumor development and progression. High expression of insulin growth factor binding protein-1 (Igfbp1) and Serine proteinase inhibitor A1 (Serpina1), and low levels or absence of Wt1 gene expression were exclusive to liver metastatic lesion samples. Conclusion: We identified Igfbp1, Serpina1 and Wt1 genes that are likely to be clinically useful biomarkers for prognostic or therapeutic purposes in metastatic pancreatic cancer, particularly in pancreatic cancer where c-Myc is overexpressed. [ABSTRACT FROM AUTHOR]

While the role of CC chemokines in mononuclear cell trafficking and activation has been well studied, the functional role of CC chemokines in the regulation of polymorphonuclear neutrophil (PMN) recruitment in vivo has not been widely examined. Bacterial infection of the cornea (keratitis) is a relatively common, sometimes sight-threatening disease, which features acute inflammation with ulceration and PMN infiltration. Here, we demonstrate a critical role for the chemokines, CCL2 and CCL3, in the Pseudomonas aeruginosa-induced model of corneal infection in BALB/c mice. Treatment of mice with anti-CCL2 or anti-CCL3 antibodies resulted in a significant reduction in severity of corneal damage and PMN infiltration at 1 and 7 days after infection compared to control antibody-treated eyes, but did not significantly alter the rate of bacterial clearance from the cornea. Our findings provide strong evidence that CCL2 and CCL3 are critical regulators of PMN recruitment, and may lead to therapeutic strategies via targeting of the CC chemokines, CCL2 and CCL3, in the management of P. aeruginosa keratitis.Immunology and Cell Biology (2007) 85, 525–531; doi:10.1038/sj.icb.7100082; published online 19 June 2007 [ABSTRACT FROM AUTHOR]

Abstract: The Wnt signal acts by binding to Frizzled receptors, with the subsequent activation of two different signal transduction cascades, the canonical and the non-canonical Wnt pathways, involved in cell growth, differentiation, migration and fate. The canonical pathway functions through the translocation of β-catenin to the nucleus and the activation of TCF/LEF transcription factors; it plays an important role in developmental patterning and cell fate decisions during embryogenesis. The non-canonical Wnt pathway is responsible for the planar cell polarity process in invertebrates, and for the convergent-extension movements during vertebrate gastrulation. The final effect of the non-canonical Wnt pathway is the rearrangement of the cell cytoskeleton, through the activation of the subfamily of Ras-like small GTPases. In a recent report we described for the first time the isolation of a Wnt-related gene, Sd-Frizzled, from the most basal animal phylum, the Porifera. In the present study we report the isolation and phylogenetic characterization of several Wnt pathway-related genes from the sponge Suberites domuncula: Sd-TCF/LEF, Sd-GSK3, a recently discovered molecule with a putative function as a Wnt regulator (Sd-LZIC), the small Rho GTPases Sd-RhoA, Sd-Cdc42, and their effector Sd-mrlc. Also the isolation of a secreted frizzled related protein sFRP from another sponge species (Lubomirskia baicalensis) is reported. [Copyright &y& Elsevier]

The article offers information on the University Grants Commission-Consortium for Academic Research and Ethics (CARE) initiative to promote research quality, integrity and publication ethics. It discusses the challenges in increased incidence of compromised publication ethics and deteriorating academic integrity. It mentions the vastness, diversity and complexity of the Indian higher education system.

Purpose. Antibody neutralization studies have shown that in Pseudomonas aeruginosa corneal infection, IL-1β is critical to regulation of the host inflammatory response, but mechanisms remain undetermined. To elucidate these mechanisms, caspase-1 knockout (ICE -/- ) mice, that do not release mature IL-1β after endotoxin challenge, were tested. Methods. Clinical scores, MPO activity (for PMN quantitation), bacterial plate count, semiquantitative RT-PCR, ELISA and TUNEL staining were used to characterize the inflammatory response after infection in knockout and C57BL/6 (B6) wild type mice. Results. Clinical scores were significantly reduced in ICE -/- vs. B6 mice at 3, 5 and 7 days postinfection (p.i.). The decreased inflammatory response of ICE -/- mice was striking at 1 day p.i., and bacterial load also was significantly reduced in the cornea of the knockout mice at 3-7 days p.i. Knockout mice exhibited significantly increased mRNA and protein levels for IL-1Ra, the physiological regulator of IL-1 activity, and in addition, a significant increase in the number of apoptotic cells were quantitated in the corneal epithelium of ICE -/- vs. B6 mice at 1 day p.i. Conclusions. These data provide evidence that bacterial infection in the cornea of ICE -/- mice induces a reduced inflammatory response by: reduction in PMN and cytokines and chemokines that attract these cells to the cornea; enhanced apoptotic cell death in the infected epithelium; and increased IL-1Ra levels. The data also confirm the importance of IL-1 regulation in this model and suggest that ICE inhibition may be an attractive ancillary therapeutic strategy to control the host response to this pathogen. [ABSTRACT FROM AUTHOR]

Summary Pseudomonas aeruginosa ocular infection causes extensive corneal neovascularization. The purpose of the present study was to investigate the role of the angiogenic factors macrophage inflammatory protein-2 (MIP-2) and vascular endothelial growth factor (VEGF) in the regulation of corneal neovascularization during P. aeruginosa ocular infection. After administering anti-MIP-2 antibody or control antibody, mouse corneas were challenged with P. aeruginosa . The expression of MIP-2 and VEGF was detected using an ELISA from ocular homogenates. Corneal neovascularization was examined by histology. The cellular sources of MIP-2 and VEGF were identified by immunohistochemistry. In addition, protein expression of MIP-2 and VEGF in isolated corneas was measured to determine the ability of the cornea to produce these two mediators. Results showed that the expression of MIP-2 and VEGF was significantly (P < 0.05) elevated after bacterial infection, and high levels of these two mediators paralleled the extensive corneal neovascularization seen at later stages of the infection. Anti-MIP-2 antibody treatment resulted in a significant (P < 0.05) reduction in VEGF expression and in corneal neovascularization. Both corneal resident cells and infiltrating neutrophils had the ability to produce MIP-2 and VEGF after stimulation. The present study demonstrates that both MIP-2 and VEGF are important mediators in the regulation of corneal neovascularization caused by P. aeruginosa infection, and that MIP-2 regulates the production of VEGF. [ABSTRACT FROM AUTHOR]

Abstract Ocular infection with Pseudomonas aeruginosa triggers extensive host inflammatory response and corneal damage. The purpose of present study was to investigate the gene expression of pro-inflammatory mediators interleukin (IL)-1β, IL-6, tumour necrosis factor-α (TNF-α), macrophage inflammatory protein (MIP)-2 and cytokine-induced neutrophil chemo­attractant (KC) in the mouse eye challenged with P. aeruginosa. Scratched mouse corneas were infected with three phenotypes of P. aeruginosa individually. Total RNA was extracted from mouse eyes at 4 h, 8 h, 16 h and 24 h post-challenge. Single stranded cDNA was synthesized from total RNA by reverse transcription and then subjected to poly­merase chain reaction (PCR) using specific primers for IL-1β, IL-6, TNF-α, MIP-2 and KC. Results revealed three patterns of cytokines and chemokines expression in response to ocular infection with three phenotypes of P. aeruginosa . Ocular infection with the invasive strain induced the highest levels of IL-1β, IL-6, MIP-2 and KC mRNA, followed by the infection with the cytotoxic strain. Ocular infection with the CLARE strain induced the lowest levels of IL-1β, IL-6, MIP-2 and KC mRNA. The expression of TNF-α mRNA was very low and irregular following P. aeruginosa challenge. These data indicate that over-expression of pro-inflammatory cytokines and chemo­k­ines may represent a vigorous immune response and therefore may contribute to corneal damage during P. aeruginosa infection. [ABSTRACT FROM AUTHOR]

ABSTRACT Macrophage migration inhibitory factor (MIF) is a recently rediscovered pro-inflammatory cytokine, and has been shown to play a role in the regulation of neutrophil chemokines and angiogenesis. Corneal epithelial and endothelial cells have been shown to express MIF. This study evaluated the expression of MIF during Pseudomonas keratitis in mice and in vitro using a corneal epithelial cell line. Three strains of P. aeruginosa, 6294 (invasive strain), 6206 (cytotoxic strain) and Paer1 (non- infectious strain) were used. Both cytotoxic and invasive strains were isolated from human corneal ulcers and the Paer1 strain was isolated from a non-infectious condition. Following challenge in mouse corneas or a corneal epithelial cell line, corneal homogenates or lysed corneal epithelial cells were used to isolate RNA. Migration inhibitory factor mRNA expression in the mouse cornea or human corneal epithelial cells was examined by reverse transcription–polymerase chain reaction analysis, and was found to be expressed as early as 4 h after the injury (scratch controls) or infection in the mouse corneas. Migration inhibitory factor mRNA in scratch controls and Paer1-inoculated corneas showed peak levels at 4 h post-challenge and this dropped by 24 h post-challenge. Corneas challenged with invasive and cytotoxic strains showed peak expression 24 h post-challenge. Migration inhibitory factor mRNA levels were significantly higher in invasive and cytotoxic strain inoculated corneas compared to Paer1 inoculated corneas. Challenging the corneal epithelial cell line with Pseudomonas 6294 and 6206 strains induced peak expression at 8 h and levels were decreased by 12 h. Epithelial cells inoculated with recombinant human interleukin-1β protein induced very high levels of MIF mRNA at all time points compared to infected and control corneal epithelial cells. High expression of MIF in the infected corneas suggests that it may have a role in the pathogenesis of corneal disease induced by invasive and cytotoxic strains of P. aeruginosa. [ABSTRACT FROM AUTHOR]

This proof-of-concept study investigates the immune effects in metastatic breast cancer (MBC) patients after “vaccination” with activated T cells (ATC) armed with anti-CD3 x anti-HER2 bispecific antibody (HER2 BATs) followed by immune consolidation with immune ATC “boost” after high dose chemotherapy (HDC) and autologous stem cell transplant (SCT). Approximately 2 weeks after completion of vaccination portion of the study, immune T cells were obtained by leukopheresis, activated and expanded ex vivo and re-infused after HDC and SCT to test the hypothesis that transfer of immune unarmed ATC would accelerate reconstitution of anti-tumor activity after SCT. Eight metastatic breast cancer (MBC) patients received 8 infusions of HER2 BATs, low dose IL-2, and GM-CSF in the first part of the protocol to induce adaptive cellular and humoral responses. In the “boost” portion of the protocol, 6 of 8 patients received multiple infusions of unarmed ATC post SCT. There were no dose-limiting toxicities or delays in engraftment. Four of 6 patients tested for the immune correlative studies exhibited increases in anti-breast cancer (BrCa) cytotoxicity, antigen specific IFN-γ Elispots, anti-BrCa antibodies and increased IL-12 and Th1 serum cytokine levels after HER2 BATs infusions. Anti-BrCa tumor responses were seen as early as 2 weeks after SCT and persisted up to 2 years post-SCT. One out of 6 patients’ rapidly progressed and showed poor immune responses and high Th2 cytokine levels. There was a significant correlation (p < 0.002) between time to progression (TTP) and anti-BrCa cytotoxicity by immune T cells. This is the first study to show that adoptive transfer of immune T cells after SCT accelerates reconstitution of anti-BrCa specific immunity and correlates with delay TTP. [ABSTRACT FROM AUTHOR]

Objectives: To assess the knowledge and attitude towards contraception, especially PPIUCD in women delivering at tertiary care Government Hospital of Madhya Pradesh and to look for awareness and reason of refusal of PPIUCD. Method: Study is a cross sectional study carried out in the Department of Obstetrics and Gynaecology, NSCB Medical College Jabalpur Madhya Pradesh India. All postnatal women (delivered at our hospital) consented to participate in the study were included. Patients with Haemoglobin <10 gm%, preterm premature rupture of membranes >18 hours, postpartum haemorrhage, history of fever during labor and delivery, women with fibroid or uterine malformation were excluded from study. A total of 360 women were included in the study. Patient asked to fill questionnaire containing both Likert scale and open-ended questions to assess knowledge and attitude towards post placental IUCD and other methods of contraception. At the time of delivery all women counselled for post placental IUCD, and willing patients had IUCD inserted. Those who refused their reason for refusal were recorded. Data entry was done using SPSS version 17.0 for statistical analysis. Continuous variables were reported using mean (standard deviation), and categorical variables were reported using percentage. Result: In present study, maximum number (65.27%) of patients were unaware of any type of contraception. 30.55% patients were aware of IUCD and 16.38% patients have knowledge of post placental IUCD while only 2.7% have ever used PPIUCD. Among reasons for refusal of PPIUCD, 38.8% patients not willing for PPIUCD, 61.1% others not willing, husband refusal was in 41.6% patents. Common myth associated with PPIUCD is menorrhagia. Conclusion: According to present study, awareness for copper T devices is very less among patients and also patients are not aware of postplacental intra uterine devices. Therefore, counselling of patient especially during their antenatal visits for contraception is very important. [ABSTRACT FROM AUTHOR]

Introduction: Escherichia coli (E.coli) and Klebsiella pneumoniae (K.pneumoniae) are the most common organisms isolated from clinical specimens. Increasing Multi-Drug Resistance (MDR) in these Gram-negative organisms has caused considerable therapeutic challenges in clinical practice. This has recently revived interest in colistin as a remedial option. The increasing use of colistin entails the provision of rapid and reliable methods for colistin susceptibility testing. Aim: To evaluate the performance of rapid polymyxin Nordmann-Poirel (NP) test and VITEK-2 for detection of colistin resistance. Materials and Methods: Two methods of colistin susceptibility testing, VITEK-2 and Rapid polymyxin NP test were compared on 310 isolates of E.coli and K.pneumoniae obtained from various clinical samples such as blood, urine, sputum, pus and endotracheal aspirates. Kappa analysis was done to evaluate the percentage agreement between Vitek-2 and Rapid Polymyxin NP tests. Results: Out of 310 isolates, 232 were E.coli and 78 were K.pneumoniae. The results of both the methods was consistent in (237/310) 76.45% cases and non-consistent in (73/310) 23.55% cases. Kappa analysis revealed that the strength of agreement between the two test was considered moderate (kappa=0.412, confidence interval: from 0.312 to 0.513). Conclusion: Rapid polymyxin NP test when compared to VITEK-2 was simple, rapid and cost-effective. Thus, it can be used in laboratories for screening of polymyxin resistance in carbapenemase-producing Gram-negative bacteria as recommended by CLSI (Clinical Laboratory Standard Institute). [ABSTRACT FROM AUTHOR]