Hyperthermia and doxorubicin release by Fol-LSMO nanoparticles induce apoptosis and autophagy in breast cancer cells.

Background: Studies on the anticancer effects of lanthanum strontium manganese oxide (LSMO) nanoparticles (NPs)-mediated hyperthermia at cellular and molecular levels are scarce. Materials & methods: LSMO NPs conjugated with folic acid (Fol-LSMO NPs) were synthesized, followed by doxorubicin-loading (DoxFol-LSMO NPs), and their effects on breast cancer cells were investigated. Results: Hyperthermia (45°C) and combination treatments exhibited the highest (∼95%) anticancer activity with increased oxidative stress. The involvement of intrinsic mitochondria-mediated apoptotic pathway and induction of autophagy was noted. Cellular and molecular evidence confirmed the crosstalk between apoptosis and autophagy, involving Beclin1, Bcl2 and Caspase-3 genes with free reactive oxygen species presence. Conclusion: The study confirmed hyperthermia and doxorubicin release by Fol-LSMO NPs induces apoptosis and autophagy in breast cancer cells.

Functioning and time utilisation by female multi-purpose health workers in South India: a time and motion study.

BACKGROUND: Auxillary nurse midwives (ANMs) are the most important frontline multi-purpose workers in rural India. This study was conducted to assess the spectrum of service delivery, time utilisation, work planning, and factors affecting functioning of ANMs in South India. METHODS: We conducted a time and motion study in three districts across two states in South India. The districts selected in such a manner that they had a considerable tribal population. We conducted multi-stage sampling to select ANMs. We directly observed 43 ANMs consecutively for six working days and in-depth interviewed all selected ANMs, their supervisors, medical officers, and district health officials. We conducted an FGD to substantiate the findings from observations and interviews. Observation findings were analysed under three broad domains: (i) programme activities, (ii) programme support activities, and (iii) other work. Time spent was calculated in median (interquartile range, IQR) minutes/ANM per week or day. Qualitative data were coded and analysed using grounded theory, and appropriate themes and sub-themes were identified. RESULTS: ANMs worked for median 7 h a day (7:10 h, non-tribal; 6:20 h, tribal). There is variation in the hours of work, the pattern of service provided and time utilisation across days of a week. ANMs spent 60% of their on-job time on programmatic activities (median 22:38 h; IQR, 20:48-27:01 h) in a week. Emphasis is more on home visits, universal immunisation, antenatal care, school health, and seasonal diseases. ANMs spent negligible time on non-communicable diseases, adolescent health, nutrition, etc. ANMs spent the remaining time in program support activities, such as meetings with seniors, community meetings, and other non-health related work. There are no renewed job description, work plans, and supervision guidelines, even with newly added programs and tasks. ANMs prioritised work as per the priorities set by the supervisors and leaders. Health administration often disrupts the regular functioning of ANMs for training, meetings and other ad hoc work. CONCLUSION: ANMs are overworked; they often multi-task and fail to deliver efficiently. The administration needs to re-assess the workload. The administration may reduce expected work, provide strong supervisory support, and make conscious efforts to pose fewer disruptions in regular working of ANMs.

Time motion study using mixed methods to assess service delivery by frontline health workers from South India: methods.

BACKGROUND: In India, amidst the increasing number of health programmes, there are concerns about the performance of frontline health workers (FLHW). We assessed the time utilisation and factors affecting the work of frontline health workers from South India. METHODS: This is a mixed methods study using time and motion (TAM) direct observations and qualitative enquiry among frontline/community health workers. These included 43 female and 6 male multipurpose health workers (namely, auxiliary nurse midwives (ANMs) and male-MPHWs), 12 nutrition and health workers (Anganwadi workers, AWWs) and 53 incentive-based community health workers (accredited social health activists, ASHAs). We conducted the study in two phases. In the formative phase, we conducted an in-depth inductive investigation to develop observation checklists and qualitative tools. The main study involved deductive approach for TAM observations. This enabled us to observe a larger sample to capture variations across non-tribal and tribal regions and different health cadres. For the main study, we developed GPRS-enabled android-based application to precisely record time, multi-tasking and field movement. We conducted non-participatory direct observations (home to home) for consecutively 6 days for each participant. We conducted in-depth interviews with all the participants and 33 of their supervisors and relevant officials. We conducted six focus group discussions (FGDs) with ASHAs and one FGD with ANMs to validate preliminary findings. We established a mechanism for quality assurance of data collection and analysis. We analysed the data separately for each cadre and stratified for non-tribal and tribal regions. RESULTS: On any working day, the ANMs spent median 7:04 h, male-MPHWs spent median 5:44 h and AWWs spent median 6:50 h on the job. The time spent on the job was less among the FLHWs from tribal areas as compared to those from non-tribal areas. ANMs and AWWs prioritised maternal and child health, while male-MPHWs were involved in seasonal diseases and school health. ASHAs visited homes to provide maternal health, basic curative care, and follow-up of tuberculosis patients. The results describe issues related with work planning, time management and several systemic, community-based and personnel factors affecting work of FLHWs. CONCLUSION: TAM study with mixed methods can help researchers as well as managers to periodically review work patterns, devise appropriate job responsibilities and improve the efficiency of health workers.

Endochondral Ossification in Critical-Sized Bone Defects via Readily Implantable Scaffold-Free Stem Cell Constructs.

The growing socioeconomic burden of musculoskeletal injuries and limitations of current therapies have motivated tissue engineering approaches to generate functional tissues to aid in defect healing. A readily implantable scaffold-free system comprised of human bone marrow-derived mesenchymal stem cells embedded with bioactive microparticles capable of controlled delivery of transforming growth factor-beta 1 (TGF-ß1) and bone morphogenetic protein-2 (BMP-2) was engineered to guide endochondral bone formation. The microparticles were formulated to release TGF-ß1 early to induce cartilage formation and BMP-2 in a more sustained manner to promote remodeling into bone. Cell constructs containing microparticles, empty or loaded with one or both growth factors, were implanted into rat critical-sized calvarial defects. Micro-computed tomography and histological analyses after 4 weeks showed that microparticle-incorporated constructs with or without growth factor promoted greater bone formation compared to sham controls, with the greatest degree of healing with bony bridging resulting from constructs loaded with BMP-2 and TGF-ß1. Importantly, bone volume fraction increased significantly from 4 to 8 weeks in defects treated with both growth factors. Immunohistochemistry revealed the presence of types I, II, and X collagen, suggesting defect healing via endochondral ossification in all experimental groups. The presence of vascularized red bone marrow provided strong evidence for the ability of these constructs to stimulate angiogenesis. This system has great translational potential as a readily implantable combination therapy that can initiate and accelerate endochondral ossification in vivo. Importantly, construct implantation does not require prior lengthy in vitro culture for chondrogenic cell priming with growth factors that is necessary for current scaffold-free combination therapies. Stem Cells Translational Medicine 2017;6:1644-1659.

Morphological analysis of palatal rugae pattern in central Indian population.

AIM: The aim of this study was to analyze the morphological study of palatal rugae pattern in a central Indian population and to determine sex differentiation. OBJECTIVES: To investigate the distinctive rugae patterns of the study population and determine the contribution of rugae patterns in gender identification. MATERIAL AND METHODS: The present cross-sectional study was conducted among a Central Indian population with a sample size of 500 participants. The study involved 250 males and 250 females who were randomly selected from the outpatient department of Oral Medicine Diagnosis and Radiology, Hitkarini Dental College and Hospital, Jabalpur, Madhya Pradesh. After collection of impression, casts were made and analyzed to evaluate the palatal rugae pattern in a central Indian population by using Thomas and Kotze classification (1983) for number, shape, direction, and unification of palatal rugae pattern. The statistical analysis was carried out using Mann-Whitney test and Chi-square (χ2) tests for categorical variables. RESULT: Males showed more number of rugae than females [P = 0.00 (≤0.001)]. Males had more number of wavy rugae pattern whereas females showed more number of straight rugae patterns [P = 0.00 (≤0.001)]. Males showed more backwardly directed rugae whereas females showed more forwardly directed rugae [P = 0.00 (≤0.001)]. The unification did not show any significant difference. CONCLUSION: This study showed that there was a significant relationship between palatoscopy, human identification, and sex determination. Thus, palatoscopy can be considered as a cost effective, easy, unique, and stable method for human identification.

Guiding Chondrogenesis and Osteogenesis with Mineral-Coated Hydroxyapatite and BMP-2 Incorporated within High-Density hMSC Aggregates for Bone Regeneration.

Since hydroxyapatite and bone morphogenetic protein-2 (BMP-2) can regulate chondrogenesis and osteogenesis, their individual and combined effects on endochondral ossification within human bone marrow-derived stem cell (hMSC) aggregates were investigated. Hydroxyapatite was presented in the form of mineral-coated hydroxyapatite microparticles (MCM) capable of controlled BMP-2 delivery. Aggregates were treated with varied BMP-2 concentrations supplemented in the media and loaded onto MCM to examine the influence of BMP-2 amount and spatial presentation on regulating chondrogenesis and osteogenesis. MCM alone induced GAG and type II collagen production by week 5 for two of three donors, and BMP-2 may have accelerated MCM-induced chondrogenesis. ALP activity and calcium content of cells-only aggregates suggest that the BMP-2-induced osteogenic response may be concentration-dependent. Treatment with MCM and BMP-2 resulted in chondrogenesis as early as week 2, which may have promoted additional mineralization by week 5, suggesting the induction of endochondral ossification. Released BMP-2 had similar if not higher levels of bioactivity compared to that of exogenous BMP-2 with regard to chondrogenesis and osteogenesis. In addition to providing localized and sustained BMP-2 delivery, MCM incorporation within aggregates yields a self-sustaining system that may be injected or implanted more rapidly to heal bone defects through endochondral ossification without extended in vitro culture.

Controlled Dual Growth Factor Delivery From Microparticles Incorporated Within Human Bone Marrow-Derived Mesenchymal Stem Cell Aggregates for Enhanced Bone Tissue Engineering via Endochondral Ossification.

Bone tissue engineering via endochondral ossification has been explored by chondrogenically priming cells using soluble mediators for at least 3 weeks to produce a hypertrophic cartilage template. Although recapitulation of endochondral ossification has been achieved, long-term in vitro culture is required for priming cells through repeated supplementation of inductive factors in the media. To address this challenge, a microparticle-based growth factor delivery system was engineered to drive endochondral ossification within human bone marrow-derived mesenchymal stem cell (hMSC) aggregates. Sequential exogenous presentation of soluble transforming growth factor-ß1 (TGF-ß1) and bone morphogenetic protein-2 (BMP-2) at various defined time courses resulted in varying degrees of chondrogenesis and osteogenesis as demonstrated by glycosaminoglycan and calcium content. The time course that best induced endochondral ossification was used to guide the development of the microparticle-based controlled delivery system for TGF-ß1 and BMP-2. Gelatin microparticles capable of relatively rapid release of TGF-ß1 and mineral-coated hydroxyapatite microparticles permitting more sustained release of BMP-2 were then incorporated within hMSC aggregates and cultured for 5 weeks following the predetermined time course for sequential presentation of bioactive signals. Compared with cell-only aggregates treated with exogenous growth factors, aggregates with incorporated TGF-ß1- and BMP-2-loaded microparticles exhibited enhanced chondrogenesis and alkaline phosphatase activity at week 2 and a greater degree of mineralization by week 5. Staining for types I and II collagen, osteopontin, and osteocalcin revealed the presence of cartilage and bone. This microparticle-incorporated system has potential as a readily implantable therapy for healing bone defects without the need for long-term in vitro chondrogenic priming. Significance: This study demonstrates the regulation of chondrogenesis and osteogenesis with regard to endochondral bone formation in high-density stem cell systems through the controlled presentation of inductive factors from incorporated microparticles. This work lays the foundation for a rapidly implantable tissue engineering system that promotes bone repair via endochondral ossification, a pathway that can delay the need for a functional vascular network and has an intrinsic ability to promote angiogenesis. The modular nature of this system lends well to using different cell types and/or growth factors to induce endochondral bone formation, as well as the production of other tissue types.

Artifacts: The downturn of CBCT image.

Cone-beam computed tomography (CBCT) has been accepted as a useful tool for diagnosis and treatment planning in dentistry. Despite a growing trend of CBCT in dentistry, it has some disadvantages like artifacts. Artifacts are discrepancies between the reconstructed visual image and the actual content of the subject which degrade the quality of CBCT images, making them diagnostically unusable. Additionally, structures that do not exist in the subject may appear within images. Such structures can occur because of patient motion, the image capture and reconstruction process. To optimize image quality, it is necessary to understand the types of artifacts. This article aims to throw light on the various types of artifacts associated with CBCT images.