Photodynamic priming with triple-receptor targeted nanoconjugates that trigger T cell-mediated immune responses in a 3D in vitro heterocellular model of pancreatic cancer

Photodynamic priming (PDP), a collateral effect of photodynamic therapy, can transiently alter the tumor microenvironment (TME) beyond the cytotoxic zone. Studies have demonstrated that PDP increases tumor permeability and modulates immune-stimulatory effects by inducing immunogenic cell death, via the release of damage-associated molecular patterns and tumor-associated antigens. Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest of cancers with a stubborn immunosuppressive TME and a dense stroma, representing a challenge for current molecular targeted therapies often involving macromolecules. We, therefore, tested the hypothesis that PDP\u27s TME modulation will enable targeted therapy and result in immune stimulation. Using triple-receptor-targeted photoimmuno-nanoconjugate (TR-PINs)-mediated PDP, targeting epidermal growth factor receptor, transferrin receptor, and human epidermal growth factor receptor 2 we show light dose-dependent TR-PINs mediated cytotoxicity in human PDAC cells (MIA PaCa-2), co-cultured with human pancreatic cancer-associated fibroblasts (PCAFs) in spheroids. Furthermore, TR-PINs induced the expression of heat shock proteins (Hsp60, Hsp70), Calreticulin, and high mobility group box 1 in a light dose and time-dependent manner. TR-PINs-mediated T cell activation was observed in co-cultures of immune cells with the MIA PaCa-2-PCAF spheroids. Both CD4+ T and CD8+ T cells showed light dose and time-dependant antitumor reactivity by upregulating degranulation marker CD107a and interferon-gamma post-PDP. Substantial tumor cell death in immune cell-spheroid co-cultures by day 3 shows the augmentation by antitumor T cell activation and their ability to recognize tumors for a light dose-dependent kill. These data confirm enhanced destruction of heterogeneous pancreatic spheroids mediated by PDP-induced phototoxicity, TME modulation and increased immunogenicity with targeted nanoconstructs

Prevalence of Transfusion Transmitted Infection in Replacement and Voluntary Blood Donor

The aim of this study is to present the status of transfusion –transmitted infections among the apparently healthy donors so as to increase the awareness of complications of blood transfusion and make the clinicians more vigilant with regard to judicious use of blood. Screening of blood is mandatory for providing safe blood. The magnitude of transfusion transmitted infections (TTI) varies from country to country depending on TTI’s load in that particular population. Transfusion transmitted infections create significant burden on health care system. Donor selection is of paramount importance because infected individuals serve as an asymptomatic reservoir and a potential source of transmission. This retrospective study was carried out in healthy blood donors in the age group of 18-60 years; study was done on blood units collected from replacement and voluntary donors. The serum samples were screened for Hepatitis B Surface Antigen (HBsAg); antibodies against HIV I and II, Hepatitis C Virus (HCV) by Chemiluminescent microparticle immuno assay (CMIA) method. Screening for Syphilis was carried out by RPR Rapid plasma reagent. Seropositivity of transfusion transmitted disease in replacement donors was 1.93% in hepatitis B surface antigen, 2.41% in hepatitis C virus, 0.09% in HIV and 1.15% in syphilis. Voluntary donors had low infectivity rate as compare to replacement donor

Synthesis, Characterization, Biological Activities and Ab-initio Study of Transition Metal Complexes of [Methyl 2-((4-chlorophenyl)(hydroxy)methyle) Acrylate]

Taking cognizance of the medicinal significance and diverse functions of synthetic Morita-Baylis-Hillman adducts (MBHA), the title ligand was synthesized and purified through column chromatography. Cr+3, Mn+2, Co+3, Ni+2, Cu+2 complexes of the ligand were synthesized under basic conditions, subjected to characterization through spectral analyses and verified with the IR spectrum that was generated computationally by the DFT B3LYP method, with 6-311++ G (d,p) basis set and Hartree Fock (HF) B3LYP method in conjunction with 3-21G(d,p) basis set. Powder XRD helped to testify crystals of the complexes. Moreover, the antibacterial, and antioxidant characteristics of MBHA and its complexes were also established. All of them were found to be active antioxidants. The antibacterial activities, examined against S. aureus, E. coli, B. pumilis and S. typhi have revealed that its Cobalt complex has an excellent potential to act against all of them. Hence, these compounds maybe having potentialities for the discovery of new, cheaper and efficient drugs against various infectious diseases. The study also uncovers the first example of utilization of MBHA towards metal complex formation

A case-control study investigating cardiovascular health in maintenance hemodialysis patients through oxidative stress biomarkers and carotid artery intima-media thickness

Introduction: Chronic kidney disease (CKD) is a major risk factor for the development of cardiovascular disease (CVD), and it is the leading cause of morbidity and mortality in end-stage renal disease (ESRD) patients receiving maintenance hemodialysis (MHD). Aim: This study aims to evaluate biomarkers of oxidative stress (OS) and carotid artery intima-media thickness as predictors of cardiovascular health among MHD patients. Materials and methods: We divided 135 participants in this prospective case-control study into three groups: group A included 45 healthy controls, group B included 45 ESRD patients receiving MHD for less than three years, and group C included 45 ESRD patients receiving MHD for more than three years. Participants aged 18–50 years, not taking antioxidant supplements, and willing to participate were included, excluding those with chronic illnesses, prior cardiac disease, or acute renal failure. Data collected included demographics, MHD duration, medical history, lipid profile, common carotid artery intima-media thickness (CCA-IMT), and some biochemical parameters such as oxidized LDL (Ox-LDL), malondialdehyde (MDA), and superoxide dismutase (SOD). Results: This study included 135 participants divided into three groups (A, B, and C) based on the MHD duration. Significant differences were observed in OS markers and lipid profiles across the groups (p<0.001). Group C exhibited the highest levels of Ox-LDL and MDA, indicating increased OS, and the lowest SOD levels compared to groups A and B. Positive correlations were found between Ox-LDL and LDL-cholesterol (LDL-C) levels, with the strongest correlation in group C (r=0.684, p<0.05). CCA-IMT progressively increased from group A to group C, with significant differences in right, left, and mean CCA-IMT (p<0.001). Multivariate analysis revealed a positive association between Ox-LDL levels and CCA-IMT (p<0.01). Conclusion: Increased OS, evident by elevated Ox-LDL and reduced antioxidant levels, is linked to unfavorable lipid profiles and carotid atherosclerosis progression in MHD patients. Prolonged MHD duration contributes to heightened OS and increased atherosclerosis development. Ox-LDL emerges as a predictor of CVD risk in this population

Effect of Berberine Phytosome on reproductive, dermatologic, and metabolic characteristics in women with polycystic ovary syndrome: a controlled, randomized, multi-centric, open-label clinical trial

Background: Berberine is a poorly absorbed natural alkaloid widely used as nutraceutical to counteract diarrhoea and to lower cholesterol and hyperglycaemia. It has also been reported to reduce signs and symptoms of polycystic ovary syndrome (PCOS).Objective: To explore, through a multi-centric, randomized, controlled and prospective study, the possible role played by a form berberine that is more easily absorbed (Berberine Phytosome®, BP) in 130 Pakistani women with a diagnosis of PCOS and fertility problems due to menstrual and ovary abnormalities.Results: Ninety days of supplementation with BP, administered at 550 mg x2/die, determined (i) resumption of regular menstruation in about 70% of women (versus 16% in the control group; p < 0.0001), (ii) normalization of the ovaries anatomy in more than 60% of women (versus 13% in the control group; p < 0.0001), (iii) acne improvement in 50% of women (versus 16% in the control group; p = 0.0409) and (iv) hirsutism reduction in 14% of women (versus 0% in the control group; p = 0.0152). The metabolic and the hormonal profiles of the women in the two groups did not significantly differentiate at the end of the study. BP was well-tolerated and no specific side-effects were registered. Respectively after one, two and 8 years of trying, three women supplemented with BP became and are currently pregnant.Conclusion: Our study showed the positive effects of BP supplementation in women with PCOS and confirmed the high safety profile of this nutraceutical.Clinical Trial Registration:https://clinicaltrials.gov/, identifier NCT0548067

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Factors influencing nurses\u27 job satisfaction and retention in public sector tertiary care hospital Karachi

Hospitals are encountering serious dilemma in provision of quality care due to prevailing shortage of nurses. Literature suggests that poor work environment, spoiled working relationships, nursing management support, workload, inadequate autonomy and unstructured organizational policies are the major reason for nurses\u27 job dissatisfaction cited in different studies. A study conducted about nurses job satisfaction identified that the nurses\u27 work satisfaction, patients\u27 satisfaction and quality of care are influenced by global dynamics of healthcare systems. Other studies conducted in developed countries explored that a substantial proportion of nurses in many countries have reported job dissatisfaction, stress and quality care deficits as factors influencing their intention to quit. The findings of one of a comparative study conducted in private and public sectors of Pakistan depict that although nurses are not satisfied with their job but the level of satisfaction and factors for grievances vary. This study is embarking upon an exploration of factors influencing job satisfaction of nurses at a public sector tertiary care hospital in Karachi. Methods: The study was conducted through qualitative exploratory design. The duration of the study was from July to September, 2016 with active data collection in a public sector tertiary care hospital of Karachi through purposive sampling. Study participants were nurses, providing direct patient care .and head nurses in different units of hospital. Data collection was carried out through Focus Group Discussions with staff nurses; Indepth Interviews with head nurses, Key Informants interview with Human Resource professional and HR policy documents were also reviewed. Study Findings: The key findings of the study identified were lack of promotion and career opportunities, lack of in-service education and trainings, professional discrimination between physicians and nurses, high work load and patient load and shortage of staff. Moreover, nurses expect recognition for their work and respect from their working relationships like physicians and supervisors in addition from patients and their families/relatives. Workload and hectic work schedule due to shortage of staff emerged as another key reason for nurses\u27 job dissatisfaction. As most of the time they had to work extra hours due to staff shortage and high patient load but unfortunately, are not rewarded accordingly. Conclusion and policy implications: Factors related to job satisfaction and retention are context specific and varies according to organizational working environment but the factors such as workload and lack of promotion and career opportunities are the common perceived factors for job dissatisfaction. This study has identified some of the significant reasons resulting in nurses\u27 job dissatisfaction and turnover with potential implications for the whole of public sector hospitals in Karachi. The study findings would help policy and health systems stakeholders including those at Federal and organizational level to initiate effective strategies to alleviate these factors leading to reduced shortage and improved retention of nurses

Dataset on the physical characterization of biopolymer coated magnetic nanoparticles

The data presented in this article is related to the research article entitled “Paclitaxel loaded magnetic nanocomposites with folate modified chitosan/carboxymethyl surface; a vehicle for imaging and targeted drug delivery” (S. Bano, M. Afzal, M.M. Waraich, K. Alamgir, S. Nazir, 2016) [1]. It contains the absorbance spectra, band gap energies of pure nickel-ferrite nano cores (NFs), and calibration curve of Paclitaxel. Thermal stability analysis of pure NFs, chitosan (CS) and carboxymethyl cellulose (CMC)-conjugated NFs samples is also included in the data

Diclofenac Sodium Inhibits Hepatic Tryptophan 2,3-Dioxygenase but Augments Brain Indoleamine 2,3-Dioxygenase Activities in Rats

Tryptophan 2,3-dioxygenase (TDO) exist only in liver while indoleamine 2, 3-dioxygenase (IDO) exists ubiquitously in the body, these are the most rate-limiting enzymes of kynurenine pathway (KP). In response to elevated levels of cortisol and pro-inflammatory cytokines, both enzymes show increase activity in patients with depression or Alzheimer disease (AD). Non-steroidal anti-inflammatory drugs may protect against both depression and AD, but observational studies have offered contradictory results. Present study evaluates the effects of anti-inflammatory diclofenac sodium (DS) on rat hepatic TDO and brain IDO activities. Adult Albino Wistar rats were divided into control and test groups, each test group received DS (2mg/kg) i.p. injection daily and were killed either after 3.5 hours (acute treatment) or after 3, 5 and 7 days (chronic treatment) while control groups received an equal volume of vehicle. Results show that TDO enzyme activity was inhibited and liver tryptophan concentrations were increased after 3 to 7 days treatment of DS; however no effect was seen on these parameters after 3.5hrs. Brain IDO activity was increased after both acute and chronic DS treatment. It is concluded that DS inhibits hepatic TDO enzyme activity following chronic treatment, while augments brain IDO activity following both acute and chronic DS treatment, this may result in rise in cerebral kynurenic acid and/or quinolinic acid concentrations. Therefore there is a need that effects of DS on kynurenine pathway should be further investigated to rule out the protective effect of DS in inflammation-induced depression and Alzheimer disease

Diclofenac Sodium Inhibits Hepatic Tryptophan 2,3-Dioxygenase but Augments Brain Indoleamine 2,3-Dioxygenase Activities in Rats

Tryptophan 2,3-dioxygenase (TDO) exist only in liver while indoleamine 2, 3-dioxygenase (IDO) exists ubiquitously in the body, these are the most rate-limiting enzymes of kynurenine pathway (KP). In response to elevated levels of cortisol and pro-inflammatory cytokines, both enzymes show increase activity in patients with depression or Alzheimer disease (AD). Non-steroidal anti-inflammatory drugs may protect against both depression and AD, but observational studies have offered contradictory results. Present study evaluates the effects of anti-inflammatory diclofenac sodium (DS) on rat hepatic TDO and brain IDO activities. Adult Albino Wistar rats were divided into control and test groups, each test group received DS (2mg/kg) i.p. injection daily and were killed either after 3.5 hours (acute treatment) or after 3, 5 and 7 days (chronic treatment) while control groups received an equal volume of vehicle. Results show that TDO enzyme activity was inhibited and liver tryptophan concentrations were increased after 3 to 7 days treatment of DS; however no effect was seen on these parameters after 3.5hrs. Brain IDO activity was increased after both acute and chronic DS treatment. It is concluded that DS inhibits hepatic TDO enzyme activity following chronic treatment, while augments brain IDO activity following both acute and chronic DS treatment, this may result in rise in cerebral kynurenic acid and/or quinolinic acid concentrations. Therefore there is a need that effects of DS on kynurenine pathway should be further investigated to rule out the protective effect of DS in inflammation-induced depression and Alzheimer disease