Study on the impact of sensitization on materiovigilance programme among pharmacy and dental postgraduate students.

BACKGROUND: Medical devices play a crucial role in patient care but entail inherent risks, necessitating the presence of materiovigilance to monitor and prevent medical device adverse events (MDAEs). The primary objective of our study is to evaluate the impact of an awareness and sensitization program regarding medical devices among participants. METHODS: A self-administered, validated knowledge, attitude, and practice (KAP) questionnaire consisting of 15 questions was distributed to study participants, and their responses were collected. The data were analyzed using SPSS software version 18. RESULTS: Out of the 182 responses received, 56% were from the Pharmacy, while 44% were from the Dental field. 64.8% of the participants were unaware of the Materiovigilance Programme of India (MvPI). However, an overwhelming 97.5% displayed a positive attitude towards reporting MDAEs. Only 5% of the participants had received training on how to report MDAEs. Furthermore, 85.71% of participants had not seen the MDAE reporting form. CONCLUSION: To improve the reporting of MDAEs, it is essential to implement educational interventions and provide training to Pharmacy and Dental postgraduate students. These measures will increase awareness and promote better understanding and implementation of materiovigilance practices.

Pulmonary hypertension in newly diagnosed obstructive sleep apnea-chronic obstructive pulmonary disease overlap syndrome patients attending a tertiary care centre-a cross-sectional analysis.

INTRODUCTION: Overlap syndrome is the association of obstructive sleep apnea (OSA) with chronic obstructive pulmonary disorder and with other chronic respiratory diseases. Patients with overlap syndrome have a worse prognosis compared with chronic obstructive pulmonary disorder or OSA alone. Additionally, patients with combined chronic obstructive pulmonary disorder and OSA are more likely to develop pulmonary hypertension and right heart failure much earlier than those without overlap. AIM: To assess the occurrence of pulmonary hypertension (PH) in newly diagnosed OSA-chronic obstructive pulmonary disorder overlap syndrome patients attending a tertiary care centre. MATERIALS AND METHODS: This cross-sectional study was conducted at Department of Pulmonary Medicine, Government Medical College, Kozhikode, Kerala, South India, among patients with OSA above 40 years of age who were proactively evaluated to pick out those with undiagnosed overlap. A period of 6 months after getting ethical clearance from June 2018 was selected as the study period. Among patients with symptoms suggestive of OSA above 40 years of age who gave the informed consent were enrolled after screening with Standard Sleep questionnaires (Berlin questionnaire, STOP BANG and Epworth Sleepiness Scale). Enrolled patients underwent routine spirometry and sleep study using the standard Level 1 overnight polysomnography (Level1 OPSG). Patients were classified in to two groups as OSA patients (group I), having an apnea hypopnea index (AHI) > 5/hr alone and the second group as those OSA patients (group II), with an obstructive spirometry pattern who were the overlap group. Arterial blood gas analysis (a sample of radial arterial blood was drawn with the patient awake and supine, and was analyzed for pH, PaCO2 and PaO2) and echocardiography (ECHO) of the two groups were compared as a non-invasive method to assess pulmonary artery hypertension and results were analyzed in a systematic manner. RESULTS: Among the 84 patients enrolled, 16.7% had overlap syndrome and the rest had OSA alone. Statistically significant higher mean weight and BMI for those with overlap syndrome compared to the OSA group were observed. Mean FVC (forced vital capacity), FEV1 (forced expiratory volume 1 s), and FEV1/FVC were lower in those with overlap syndrome compared to OSA group. The mean values of ABG parameters revealed higher PaCO2 and lower PaO2 among the group with overlap syndrome which were statistically significant. However, there was no significant difference in resting room air SaO2 value between the two groups. The mean values of sleep duration and efficiency were significantly lower in those with overlap syndrome with a p value < 0.001. The mean value of arousal and REM (rapid eye movement) sleep percentage were significantly higher among those with overlap syndrome (p < 0.001). Mean value of NREM (non-rapid eye movement) sleep percentage was lower among the group with overlap syndrome compared with the OSA group, and this difference was statistically significant. The mean AHI value of the overlap syndrome group was 39.79 ± 7.54 and this was significantly higher than the OSA group (p < 0.004). Among the 14 patients who had ECHO evidence of pulmonary hypertension, 9 (64.3%) belonged to the overlap group which shows that they are a highly vulnerable group for developing pulmonary hypertension (PH) and requires early detection and more rigorous treatment. CONCLUSION: This study confirms that OSA patients with modest daytime level of hypoxemia and mild-moderate chronic airflow limitation have a high prevalence of PH. Chronic airway obstruction may be asymptomatic in some subjects and this stresses the necessity of pulmonary function test in OSA.

Biowaste-Derived, Highly Efficient, Reusable Carbon Nanospheres for Speedy Removal of Organic Dyes from Aqueous Solutions.

The current work explores the adsorptive efficiency of carbon nanospheres (CNSs) derived from oil palm leaves (OPL) that are a source of biowaste. CNSs were synthesized at 400, 600, 800 and 1000 °C, and those obtained at 1000 °C demonstrated maximum removal efficiency of ~91% for malachite green (MG). Physicochemical and microscopic characteristics were analysed by FESEM, TEM, FTIR, Raman, TGA and XPS studies. The presence of surface oxygen sites and the porosity of CNSs synergistically influenced the speed of removal of MG, brilliant green (BG) and Congo red (CR) dyes. With a minimal adsorbent dosage (1 mg) and minimum contact time (10 min), and under different pH conditions, adsorption was efficient and cost-effective (nearly 99, 91 and 88% for BG, MG and CR, respectively). The maximum adsorption capacities of OPL-based CNSs for BG were 500 and 104.16 mg/g for MG and 25.77 mg/g for CR. Adsorption isotherms (Freundlich, Langmuir and Temkin) and kinetics models (pseudo-first-order, pseudo-second-order and Elovich) for the adsorption processes of all three dyes on the CNSs were explored in detail. BG and CR adsorption the Freundlich isotherm best, while MG showed a best fit to the Temkin model. Adsorption kinetics of all three dyes followed a pseudo-second-order model. A reusability study was conducted to evaluate the effectiveness of CNSs in removing the MG dye and showed ~92% efficiency even after several cycles. Highly efficient CNSs with surface oxygen groups and speedy removal of organic dyes within 10 min by CNSs are highlighted in this paper.

Lineage reprogramming of human adipose mesenchymal stem cells to immune modulatory i-Heps.

Pluripotent stem cell derived-hepatocytes depict fetal -hepatocyte characteristics/maturity and are immunogenic limiting their applications. Attempts have been made to derive hepatocytes from mesenchymal stem cells using developmental cocktails, epigenetic modulators and small molecules. However, achieving a stable terminally differentiated functional state had been a challenge. Inefficient hepatic differentiation could be due to lineage restrictions set during development. Hence a novel lineage reprogramming approach has been utilized to confer competence to adipose-mesenchymal stem cells (ADMSCs) to efficiently respond to hepatogenic cues and achieve a stable functional hepatic state. Lineage reprogramming involved co-transduction of ADMSCs with hepatic endoderm pioneer Transcription factor (TF)-FOXA2, HHEX-a homeobox gene and HNF4α-master TF indispensable for hepatic state maintenance. Lineage priming was evidenced by endogenous HFN4α promoter demethylation and robust responsiveness to minimal hepatic maturation cues. Induced hepatocytes (i-Heps) exhibited mesenchymal-to-epithelial transition and terminal hepatic signatures. Functional characterisation of i-Heps for hepatic drug detoxification systems, xenobiotic uptake/clearance, metabolic status and hepatotropic virus entry validated acquisition of stable hepatic state and junctional maturity Exhaustive analysis of MSC memory in i-Heps indicated loss of MSC-immunophenotype and terminal differentiation to osteogenic/adipogenic lineages. Importantly, i-Heps suppressed phytohemagglutinin-induced T-cell blasts, inhibited allogenic mixed-lymphocyte reactions (MLRs) and secreted immunomodulatory- indoleamine 2,3-dioxygenase in T-cell blast co-cultures akin to native ADMSCs. In a nutshell, the present study identifies a novel cocktail of TFs that reprogram ADMSCs to stable hepatic state. i-Heps exhibit adult hepatocyte functional maturity with robust immune-modulatory abilities rendering suitability for rigorous drug testing, hepatocyte-pathogen interaction studies and transplantation in allogenic settings.

The Yin and Yang of Immunity in Stem Cell Decision Guidance in Tissue Ecologies: An Infection Independent Perspective.

The impact of immune system and inflammation on organ homeostasis and tissue stem cell niches in the absence of pathogen invasion has long remained a conundrum in the field of regenerative medicine. The paradoxical role of immune components in promoting tissue injury as well as resolving tissue damage has complicated therapeutic targeting of inflammation as a means to attain tissue homeostasis in degenerative disease contexts. This confound could be resolved by an integrated intricate assessment of cross-talk between inflammatory components and micro- and macro-environmental factors existing in tissues during health and disease. Prudent fate choice decisions of stem cells and their differentiated progeny are key to maintain tissue integrity and function. Stem cells have to exercise this fate choice in consultation with other tissue components. With this respect tissue immune components, danger/damage sensing molecules driving sterile inflammatory signaling cascades and barrier cells having immune-surveillance functions play pivotal roles in supervising stem cell decisions in their niches. Stem cells learn from their previous damage encounters, either endogenous or exogenous, or adapt to persistent micro-environmental changes to orchestrate their decisions. Thus understanding the communication networks between stem cells and immune system components is essential to comprehend stem cell decisions in endogenous tissue niches. Further the systemic interactions between tissue niches integrated through immune networks serve as patrolling systems to establish communication links and orchestrate micro-immune ecologies to better organismal response to injury and promote regeneration. Understanding these communication links is key to devise immune-centric regenerative therapies. Thus the present review is an integrated attempt to provide a unified purview of how inflammation and immune cells provide guidance to stem cells for tissue sculpting during development, organismal aging and tissue crisis based on the current knowledge in the field.

Trends in selected birth defects among parents from below poverty line population in Karnataka during 2010-2020.

The aim of the study is to reveal the common birth defects among parents of newborns belonging to the below poverty line (BPL) category in Karnataka state (South India) by analyzing Suvarna Arogya Suraksha Trust data. In the last 10 years, 3672 kids in BPL families have been born with various birth abnormalities. It is found that 50.3% of newborns have anorectal malformations, 33.1% have hypospadias, 6.0% have diaphragmatic hernia, 5.1% have esophageal atresia, and 2.8% have intestinal atresia and obstruct. As a parent's age rises, the likelihood of having a child with birth abnormalities raise as well, particularly anorectal malformations than diaphragmatic hernia. Male newborns have a higher risk of birth defects. We hypothesized that poverty, material deprivation, and low socioeconomic profile throughout the life course among the BPL community could be some of the key reasons for poor maternal health care and related neonatal outcomes.

Expansion and characterization of bone marrow derived human mesenchymal stromal cells in serum-free conditions.

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are gaining increasing importance in the field of regenerative medicine. Although therapeutic value of MSCs is now being established through many clinical trials, issues have been raised regarding their expansion as per regulatory guidelines. Fetal bovine serum usage in cell therapy poses difficulties due to its less-defined, highly variable composition and safety issues. Hence, there is a need for transition from serum-based to serum-free media (SFM). Since SFM are cell type-specific, a precise analysis of the properties of MSCs cultured in SFM is required to determine the most suitable one. Six different commercially available low serum/SFM with two different seeding densities were evaluated to explore their ability to support the growth and expansion of BM-MSCs and assess the characteristics of BM-MSCs cultured in these media. Except for one of the SFM, all other media tested supported the growth of BM-MSCs at a low seeding density. No significant differences were observed in the expression of MSC specific markers among the various media tested. In contrary, the population doubling time, cell yield, potency, colony-forming ability, differentiation potential, and immunosuppressive properties of MSCs varied with one another. We show that SFM tested supports the growth and expansion of BM-MSCs even at low seeding density and may serve as possible replacement for animal-derived serum.

Supplementing multi-functional groups to polysulfone membranes using Azadirachta indica leaves powder for effective and highly selective acid recovery.

Moderate and eco-pleasing ion-exchange trade membranes are in need to recover acid from industrial waste. Present study is focused on incorporation of plant waste (Azadirachta indica, neem leaves powder (NP)) of different composition as filler to polysulfone (PSf) membrane matrix to achieve acid recovery. Membranes were characterized, their chemical, mechanical and thermal stabilities and effectiveness in acid recovery via diffusion has been inspected. Multi-functional groups (-COOH, -NH2, -OH, -OAc, -C = O) present in different components of NP contributes in their own means in H+ ion transportation through membrane in acid recovery. They assisted formation of hydrogen bond and provided channels for ion permeation, and facilitated selective transportation of H+ ion over Fe2+ ions and explained mechanism is in accordance with Grotthuss-type and vehicle mechanism. Membrane with 15% of NP showed better performance in terms of ion exchange capacity (IEC) and acid recovery, at optimum concentration of NP, composite the membrane showed highest IEC values of 3.9771 mmol/g, UH+ value of ≈46.499 × 10-3 m/h and greater separation factor ≈154, which is higher than commercially available DF-120 membrane. An original thought of utilizing NP in membrane matrix opens up promising opportunities for extremely straightforward, easy, cost-effective and greener methods of recovery acid.

Marginal Accuracy and Internal Fit of Dental Copings Fabricated by Modern Additive and Subtractive Digital Technologies.

The margins of copings for crowns and retainers of fixed partial dentures affect the progress of microleakage and dental caries. Failures occur due to altered fit which is also influenced by the method of fabrication. An in-vitro study was conducted to determine among the cast base metal, copy milled zirconia, computer aided designing computer aided machining/manufacturing zirconia and direct metal laser sintered copings which showed best marginal accuracy and internal fit. Forty extracted maxillary premolars were mounted on an acrylic model and reduced occlusally using a milling machine up to a final tooth height of 4 mm from the cementoenamel junction. Axial reduction was accomplished on a surveyor and a chamfer finish line was given. The impressions and dies were made for fabrication of copings which were luted on the prepared teeth under standardized loading, embedded in self-cure acrylic resin, sectioned and observed using scanning electron microscope for internal gap and marginal accuracy. The copings fabricated using direct metal laser sintering technique exhibited best marginal accuracy and internal fit. Comparison of mean between the four groups by ANOVA and post-hoc Tukey HSD tests showed a statistically significant difference between all the groups (p⟨0.05). It was concluded that the copings fabricated using direct metal laser sintering technique exhibited best marginal accuracy and internal fit. Additive digital technologies such as direct metal laser sintering could be cost-effective for the clinician, minimize failures related to fit and increase longevity of teeth and prostheses.

Eco-friendly membrane process and product development for complete elimination of chromium toxicity in wastewater.

Hydrophobic polysulphone (PSf) was reformed into a hydrophilic polymer by sulphonation (via electrophilic substitution) and was subsequently made into a composite by incorporating nano titania to reduce Cr (VI) in the concentrated feed to Cr (III), thus eliminating the hazards of Cr (VI). The modified polymer and its composites were characterized by spectroscopic and microscopic techniques. The composite membranes exhibited enhanced hydrophilicity and flux and were evaluated for the rejection of chromium. The effect of pH and interference of counter ions towards rejection was studied. The charges fixed on the surface of the membrane due to titania, support ionic interactions and facilitated the rejection process. Essentially, rejection of up to 98% was achieved. The innovation of using a bifunctional membrane for the rejection of Cr (VI) together with the removal of its toxicity by photocatalytic reduction, leading to the potential recovery of Cr (III), highlight the uniqueness of this work.

Human Mesenchymal stem cells program macrophage plasticity by altering their metabolic status via a PGE2-dependent mechanism.

Mesenchymal stem cells (MSCs) are speculated to act at macrophage-injury interfaces to mediate efficient repair. To explore this facet in-depth this study evaluates the influence of MSCs on human macrophages existing in distinct functional states. MSCs promoted macrophage differentiation, enhanced respiratory burst and potentiated microbicidal responses in naïve macrophages (Mφ). Functional attenuation of inflammatory M1 macrophages was associated with a concomitant shift towards alternatively activated M2 state in MSC-M1 co-cultures. In contrast, alternate macrophage (M2) activation was enhanced in MSC-M2 co-cultures. Elucidation of key macrophage metabolic programs in Mo/MSC, M1/MSC and M2/MSC co-cultures indicated changes in Glucose transporter1 (GLUT1 expression/glucose uptake, IDO1 protein/activity, SIRTUIN1 and alterations in AMPK and mTOR activity, reflecting MSC-instructed metabolic shifts. Inability of Cox2 knockdown MSCs to attenuate M1 macrophages and their inefficiency in instructing metabolic shifts in polarized macrophages establishes a key role for MSC-secreted PGE2 in manipulating macrophage metabolic status and plasticity. Functional significance of MSC-mediated macrophage activation shifts was further validated on human endothelial cells prone to M1 mediated injury. In conclusion, we propose a novel role for MSC secreted factors induced at the MSC-macrophage interface in re-educating macrophages by manipulating metabolic programs in differentially polarized macrophages.

Hematometra and acute abdomen.

We report a case of a young woman who presented as acute abdomen due to hematometra resulting from cervical fibroid. This uncommon cause of acute abdominal pain should be considered in women especially with amenorrhea.

Pro-inflammatory cytokines, IFNgamma and TNFalpha, influence immune properties of human bone marrow and Wharton jelly mesenchymal stem cells differentially.

BACKGROUND: Wharton's jelly derived stem cells (WJMSCs) are gaining attention as a possible clinical alternative to bone marrow derived mesenchymal stem cells (BMMSCs) owing to better accessibility, higher expansion potential and low immunogenicity. Usage of allogenic mesenchymal stem cells (MSC) could be permissible in vivo only if they retain their immune properties in an inflammatory setting. Thus the focus of this study is to understand and compare the immune properties of BMMSCs and WJMSCs primed with key pro-inflammatory cytokines, Interferon-gamma (IFNgamma) and Tumor Necrosis Factor-alpha (TNFalpha). METHODOLOGY/PRINCIPAL FINDINGS: Initially the effect of priming on MSC mediated suppression of alloantigen and mitogen induced lymphoproliferation was evaluated in vitro. Treatment with IFNgamma or TNFalpha, did not ablate the immune-suppression caused by both the MSCs. Extent of immune-suppression was more with WJMSCs than BMMSCs in both the cases. Surprisingly, priming BMMSCs enhanced suppression of mitogen driven lymphoproliferation only; whereas IFNgamma primed WJMSCs were better suppressors of MLRs. Further, kinetic analysis of cytokine profiles in co-cultures of primed/unprimed MSCs and Phytohematoagglutinin (PHA) activated lymphocytes was evaluated. Results indicated a decrease in levels of pro-inflammatory cytokines. Interestingly, a change in kinetics and thresholds of Interleukin-2 (IL-2) secretion was observed only with BMMSCs. Analysis of activation markers on PHA-stimulated lymphocytes indicated different expression patterns in co-cultures of primed/unprimed WJMSCs and BMMSCs. Strikingly, co-culture with WJMSCs resulted in an early activation of a negative co-stimulatory molecule, CTLA4, which was not evident with BMMSCs. A screen for immune suppressive factors in primed/unprimed WJMSCs and BMMSCs indicated inherent differences in IFNgamma inducible Indoleamine 2, 3-dioxygenase (IDO) activity, Hepatocyte growth factor (HGF) and Prostaglandin E-2 (PGE2) levels which could possibly influence the mechanism of immune-modulation. CONCLUSION/SIGNIFICANCE: This study demonstrates that inflammation affects the immune properties of MSCs distinctly. Importantly different tissue derived MSCs could utilize unique mechanisms of immune-modulation.

Involvement of oxidative and nitrosative stress in modulation of gene expression and functional responses by IFNgamma.

IFNgamma is a potent immunomodulator which plays important roles in host defense. IFNgamma modulates transcription of growth-related genes [N-myc downstream regulator 1, growth arrest and DNA damage inducible gamma and inhibitor of DNA binding 2 (Id2)], which is followed by increased growth suppression in the mouse hepatoma cell line, H6. Further studies revealed modulation of genes involved in oxidative and nitrosative stress (iNos, gp91phox and Catalase) and increased generation of reactive oxygen species (ROS) and reactive nitrogen intermediates (RNIs) upon IFNgamma treatment. High amounts of ROS and RNI are responsible for IFNgamma-mediated reduction in cell growth as this process is blocked, using either diphenylene iodonium (DPI), an inhibitor of flavin-containing NADPH oxidases, or N-methyl L-arginine (LNMA), an inhibitor of nitric oxide synthase. Based on studies with LNMA and DPI, IFNgamma-modulated genes can be categorized into two distinct sets: oxidative and nitrosative stress independent (transporter associated with antigen processing 2, Cd80, Lmp10 and Icosl) and oxidative and nitrosative stress dependent (iNos, gp91phox, Catalase and Id2). In addition, DPI or LNMA blocked IFNgamma-induced activation of Ras, demonstrating the involvement of oxidative and nitrosative stress. Manumycin A, a farnesyl transferase inhibitor, blocked Ras activation and reduced NADPH oxidase activity and ROS amounts leading to increased cell growth in the presence of IFNgamma. Notably, the IFNgamma-induced MHC class I levels are not modulated in cells treated with DPI, LNMA or manumycin A. Together, these results delineate the role of high amounts of ROS, RNI and Ras activation in modulating expression of some genes and, thereby, function by IFNgamma. The implications of these results during modulation of immune responses by IFNgamma are discussed.

A novel DDS using nonlinear ROM addressing with improved compression ratio and quantization noise.

This paper presents a novel direct digital frequency synthesis (DDFS) ROM compression technique based on two properties of a sine function: (a) piecewise linear technique to approximate a sinusoid, and (b) variation in the slope of the sinusoid at different phase angles. In the proposed DDFS architecture the ROM stores a few of the sinusoidal values, and the interpolation points between the successive stored values are calculated using linear and nonlinear addressing schemes. The nonlinear addressing scheme is used to adaptively vary the number of interpolation points as the slope of the sinusoid changes, leading to a greatly reduced ROM size. The proposed architecture achieves a high compression ratio with a spurious response comparable to that of recent ROM compression techniques. To validate the proposed DDS architecture, the linear, nonlinear, and conventional DDS ROM architectures were implemented in a Xilinx Spartan II FPGA and their spurious performances were compared.

The MHC-encoded class I molecule, H-2Kk, demonstrates distinct requirements of assembly factors for cell surface expression: roles of TAP, Tapasin and beta2-microglobulin.

Major histocompatibility complex encoded class I (MHC-I) molecules display peptides derived from endogenous proteins for perusal by CD8+ T lymphocytes. H6, a mouse hepatoma cell line, expresses low levels of surface H-2Dd but not H-2Kk. Surface H-2Dd molecules are unstable and their levels, but not H-2Kk, are induced at 22 degrees C. Immunoprecipitation experiments revealed that H-2Kk, H-2Dd and beta2-microglobulin (beta2m) are expressed intracellularly; however no conformed MHC-I are present. Transcriptional profiling of factors required for MHC-I assembly demonstrated greatly reduced levels of the Transporter associated with antigen processing (Tap)2 subunit. The role of key assembly molecules in the MHC-I pathway was investigated by ectopic expression studies. Overexpression of beta2m enhanced surface H-2Dd, but not H-2Kk, levels whereas overexpression of TAP2 rescued surface H-2Kk, but not H-2Dd, levels. Interestingly, Tapasin plays a dual role: first, in quality control by reducing the induced surface expression of TAP2-mediated H-2Kk and beta2m-mediated H-2Dd levels. Secondly, Tapasin overexpression increases Tap2 transcripts and cooperates with TAPl or human beta2m to enhance surface H-2Kk expression; this synergy is TAP-dependent as demonstrated by infected cell protein 47 (ICP47) inhibition studies. Unlike the well studied H-2 MHC-I alleles, H-2Kb, H-2Db, H-2Kd and H-2Dd, a functional TAP is "essential" for H-2Kk cell surface expression.