Clinical Profile, Complications and Trends of Ocular Anaesthesia in a Multi-tier Ophthalmology Network in India: An Eight-Year Experience.

INTRODUCTION: To describe the clinical profile, complications and trends of ocular anaesthesia in a multi-tier ophthalmology network in India. METHODS: This retrospective hospital-based study included 417,622 patients presenting between January 2013 and December 2020. Patients who were administered either topical, local or general anaesthesia for ocular surgery in at least one eye were included as cases. The data were collected using an electronic medical record system. RESULTS: Among the 417,622 patients, local anaesthesia was administered to 280,638, (67.2%) patients and was the most commonly administered type followed by topical anaesthesia in 84,117 (20.14%) patients. The most common complication encountered in administering local anaesthesia was retrobulbar haemorrhage in 103 (0.037%) patients followed by lid haematoma in 49 (0.017%) patients. Tooth damage occurred in 40 (0.076%) patients followed by delayed recovery in 30 (0.057%) patients during general anaesthesia. The trend of local anaesthesia decreased (83.48% vs 53.36%), whereas the trend of topical anaesthesia increased (8.61% vs 32.42%) over the study period. CONCLUSION: There is a notable trend towards the adoption of less invasive anaesthetic methods, particularly in common surgeries such as cataract, intravitreal injection, and vitreoretinal surgery. However, despite this trend, a significant proportion of oculoplastic/orbital surgeries, trauma, and strabismus surgeries continue to be performed under general anaesthesia. These observations underscore the ongoing evolution of ocular anaesthesia practices, reflecting advancements in surgical techniques and patient preferences.

Evolution of anodised titanium for implant applications.

Anodised titanium has a long history as a coating structure for implants due to its bioactive and ossified surface, which promotes rapid bone integration. In response to the growing literature on anodised titanium, this article is the first to revisit the evolution of anodised titanium as an implant coating. The review reports the process and mechanisms for the engineering of distinctive anodised titanium structures, the significant factors influencing the mechanisms of its formation, bioactivity, as well as recent pre- and post-surface treatments proposed to improve the performance of anodised titanium. The review then broadens the discussion to include future functional trends of anodised titanium, ranging from the provision of higher surface energy interactions in the design of biocomposite coatings (template stencil interface for mechanical interlock) to techniques for measuring the bone-to-implant contact (BIC), each with their own challenges. Overall, this paper provides up-to-date information on the impacts of the structure and function of anodised titanium as an implant coating in vitro and in/ex vivo tests, as well as the four key future challenges that are important for its clinical translations, namely (i) techniques to enhance the mechanical stability and (ii) testing techniques to measure the mechanical stability of anodised titanium, (iii) real-time/in-situ detection methods for surface reactions, and (iv) cost-effectiveness for anodised titanium and its safety as a bone implant coating.

Challenges of 3D printing technology for manufacturing biomedical products: A case study of Malaysian manufacturing firms.

Additive manufacturing has attracted increasing attention worldwide, especially in the healthcare, biomedical, aerospace, and construction industries. In Malaysia, insufficient acceptance of this technology by local industries has resulted in a call for government and local practitioners to promulgate the development of this technology for various industries, particularly for biomedical products. The current study intends to frame the challenges endured by biomedical industries who use 3D printing technology for their manufacturing processes. Qualitative methods, particularly in-depth interviews, were used to identify the challenges faced by manufacturing firms when producing 3D printed biomedical products. This work was able to identify twelve key challenges when deploying additive manufacturing in biomedical products and these include issues related to binder selection, poor mechanical properties, low-dimensional accuracy, high levels of powder agglomeration, nozzle size, distribution size, limited choice of materials, texture and colour, lifespan of materials, customization of fit and design, layer height, and, lastly, build-failure. Furthermore, there also are six challenges in the management of manufacturing biomedical products using 3D printing technology, and these include staff re-education, product pricing, limited guidelines, cyber-security issues, marketing, and patents and copyright. This study discusses the reality faced by 3D printing players when producing biomedical products in Malaysia, and presents a primary reference for practitioners in other developing countries.

Syntheses of hydroxyapatite from natural sources.

Waste materials from natural sources are important resources for extraction and recovery of valuable compounds. Transformation of these waste materials into valuable materials requires specific techniques and approaches. Hydroxyapatite (HAp) is a biomaterial that can be extracted from natural wastes. HAp has been widely used in biomedical applications owing to its excellent bioactivity, high biocompatibility, and excellent osteoconduction characteristics. Thus, HAp is gaining prominence for applications as orthopaedic implants and dental materials. This review summarizes some of the recent methods for extraction of HAp from natural sources including mammalian, aquatic or marine sources, shell sources, plants and algae, and from mineral sources. The extraction methods used to obtain hydroxyapatite are also described. The effect of extraction process and natural waste source on the critical properties of the HAp such as Ca/P ratio, crystallinity and phase assemblage, particle sizes, and morphology are discussed herein.

Interpretation of Kidney Biopsy in Indian Patients Older than 60 Years: A Tertiary Care Experience.

The adult population above the age of 60 years has significantly increased in India, with a life expectancy of 68.4 years in 2016. Data regarding the renal histopathology in these patients are scarce though the number of native kidney biopsies done in this subset of population is increasing. The present study is a retrospective analysis of 231 biopsies from a total of 700 biopsies, from patients above 60 years of age (M = 65.8%; F = 34.2%) with a mean age of 64 ± 6.03 years. The indications for kidney biopsy included nephrotic syndrome (NS) (30.4%), nephritic syndrome (19.1%), rapidly progressive renal failure (11.7%), acute kidney injury (AKI) (15.7%), and acute worsening of preexisting chronic kidney disease (CKD) (23%). The median percentage of glomerulosclerosis was 22% (5%-45%), and interstitial fibrosis and tubular atrophy was 30% (10%-50%). The most common cause for nephrotic syndrome was membranous nephropathy (31.4%) and for nephritic syndrome was benign arterionephrosclerosis (22.7%). Postinfectious glomerulonephritis (29.6%) was the leading cause for rapidly progressive renal failure. Acute injury on CKD was notable in patients with diabetic nephropathy (30.2%). The predominant causes for AKI were acute tubulointerstitial nephritis (33.3%), acute tubular necrosis (22.2%), and acute pyelonephritis (19.4%). The biopsy proven histopathological features enabled us in tailoring the therapy. None of the patients developed life-threatening complications following ultrasonography-guided biopsy.

An Unusual Association of Renal Cell Carcinoma and Renal Malakoplakia with Focal Segmental Glomerulosclerosis in an Elderly Patient.

The association of malignancy and glomerulonephritis may be missed, especially in elderly patients. Here, we report a case of eosinophilic variant of renal cell carcinoma and renal parenchymal malakoplakia discovered on renal biopsy in a patient with steroid-dependent nephrotic syndrome. The presence of malakoplakia in our biopsy was probably due to systemic steroid therapy for glomerulonephritis, presence of concomitant asymptomatic urinary tract infection, and/or history of diabetes mellitus. The patient had remission of proteinuria following laparoscopic removal of the tumor, indicating probable remission of glomerulonephritis.

Renal allograft eosinophilia: An unusual presentation of sudden graft dysfunction.

We present a case of sudden allograft dysfunction 11 months after renal transplantation which presented as severe peripheral and allograft eosinophilia and was managed as a case of an acute cellular rejection with significant interstitial graft eosinophilic infiltration. Patient had partial response to antirejection therapy and eventually ended up in a chronic allograft dysfunction.

Comparison of Simultaneous Nitrification and Denitrification for Three Different Reactors.

Discharge of high NH4-N containing wastewater into water bodies has become a critical and serious issue due to its negative impact on water and environmental quality. In this research, the performance of three different reactors was assessed and compared with regard to the removal of NH4-N from wastewater. The highest nitrogen removal efficiency of 98.3% was found when the entrapped sludge reactor (ESR), in which the sludge was entrapped in polyethylene glycol polymer, was used. Under intermittent aeration, nitrification and denitrification occurred simultaneously in the aerobic and anaerobic periods. Moreover, internal carbon was consumed efficiently for denitrification. On the other hand, internal carbon consumption was not found to occur in the suspended sludge reactor (SSR) and the mixed sludge reactor (MSR) and this resulted in nitrogen removal efficiencies of SSR and MSR being 64.7 and 45.1%, respectively. Nitrification and denitrification were the main nitrogen removal processes in the aerobic and anaerobic periods, respectively. However, due to the absence of sufficient organic carbon, denitrification was uncompleted resulting in high NO3-N contents in the effluent.

Investigation of the effects of hydrogenotrophic denitrification and anammox on the improvement of the quality of the drinking water supply system.

A drinking water supply system operates at Chyasal (in the Kathmandu Valley, Nepal) for purifying the groundwater that has high levels of ammonium nitrogen (NH4-N). However, high NO3-N concentrations were seen in the water after treatment. To further improve the quality of the drinking water, two types of attached growth reactors were developed for the purification system: (i) a hydrogenotrophic denitrification (HD reactor) and (ii) a concurrent reactor with anammox and hydrogenotrophic denitrification (AnHD reactor). For the HD reactor fed by water containing NO3-N, the denitrification efficiency was high (95-98%) for all NO3-N feed rates (20-40 mg/L). The nitrite-nitrogen (NO2-N) and nitrate-nitrogen (NO3-N) concentrations in the effluent were ∼0.5 mg/L. On the other hand, the AnHD reactor fed with water containing NH4-N and NO2-N was operated under varying flow rates of H2(30-70 mL/min) and intermittent supply periods (1-2 h). The efficiency of the anammox process was found to increase with decreasing H2flow rates or with increasing intermittency of the H2supply, while the efficiency of denitrification decreased under these conditions. For the optimal condition of 1.5 h intermittent H2supply, the anammox and denitrification efficiencies of the AnHD reactor reached 80% and 42%, respectively, while the concentrations of both NH4-N and NO2-N in the effluent were <1.0 mg/L, and no NO3-N was detected. From the experimental results, it is clear that both HD and AnHD reactors can function as efficient and critical units of the water purification system.

Carers' perspectives of a weight loss intervention for adults with intellectual disabilities and obesity: a qualitative study.

BACKGROUND: To date, no studies have explored the role of carers in supporting adults with intellectual disabilities (ID) and obesity during a weight loss intervention. The present study explored perceptions of carers supporting adults with ID, as they participated in a 6-month multi-component weight loss intervention (TAKE 5). METHODS: Semi-structured interviews were used to explore the experiences of 24 carers. The transcripts were analysed qualitatively using thematic analysis. RESULTS: Three themes emerged from the analysis: carers' perceptions of participants' health; barriers and facilitators to weight loss; and carers' perceptions of the weight loss intervention. Data analysis showed similarities between the experiences reported by the carers who supported participants who lost weight and participants who did not. Lack of sufficient support from people from the internal and external environment of individuals with ID and poor communication among carers, were identified as being barriers to change. The need for accessible resources tailored to aid weight loss among adults with ID was also highlighted. CONCLUSION: This study identified specific facilitators and barriers experienced by carers during the process of supporting obese adults with ID to lose weight. Future research could utilise these findings to inform appropriate and effective weight management interventions for individuals with ID.

Smoking cessation during pregnancy: the influence of partners, family and friends on quitters and non-quitters.

This research compared pregnant quitters' and non-quitters' accounts of how partners, family and friends influenced their smoking cessation attempts. Qualitative secondary data analysis was carried out on a purposive sample of motivational interview transcripts undertaken by research midwives with pregnant women as part of SmokeChange, a smoking cessation intervention. Interviews with all quitters in the intervention group (n = 12) were analysed comparatively with interviews from a matched sample of non-quitters (n = 12).The discourses of both revealed similarity in how their partners, family and friends influenced their cessation efforts: salient others were simultaneously perceived by both groups of women as providing drivers and barriers to quit attempts; close associates who smoked were often perceived to be as supportive as those who did not. However, women who quit smoking during pregnancy talked more about receiving active praise/encouragement than those who did not. While close associates play an important role in women's attempts to stop smoking during pregnancy, the support they provide varies; further research is needed to develop a better understanding of how key relationships help or hinder cessation during pregnancy.

Getting beyond outcomes: a realist approach to help understand the impact of a nutritional intervention during smoking cessation.

OBJECTIVES: This paper discusses the benefits that a 'realist' approach can bring to an outcome study using the example of a nutritional intervention offered as an adjunct to the existing smoking cessation programmes to limit post-cessation weight gain. SUBJECTS AND SETTING: Participants of a smoking cessation programme in areas of deprivation in the north, south and west of Glasgow. RESULTS: A realist approach enabled the development of a framework able to investigate both implementation and outcomes of the intervention. Drawing on theoretical and experiential knowledge, context-mechanism-outcome hypotheses were developed for further testing at later stages of evaluation. This will focus the further stages of evaluation on testing these specific hypotheses using outcome data collected at the end of the intervention. CONCLUSION: Adopting such an evaluation approach enables integration of process and outcome data that will refine our understanding of contexts and mechanisms, which are associated with these behavioural changes. It can aid further policy decisions by identifying the type of participant and circumstances that are associated with positive outcomes and those subgroups of participants that can be targeted more effectively using other approaches.

Interleukin 17 induces cartilage collagen breakdown: novel synergistic effects in combination with proinflammatory cytokines.

OBJECTIVE: To investigate whether interleukin 17 (IL17), derived specifically from T cells, can promote type II collagen release from cartilage. The ability of IL17 to synergise with other proinflammatory mediators to induce collagen release from cartilage, and what effect anti-inflammatory agents had on this process, was also assessed. METHODS: IL17 alone, or in combination with IL1, IL6, oncostatin M (OSM), or tumour necrosis factor alpha (TNFalpha), was added to bovine nasal cartilage explant cultures. Proteoglycan and collagen release were determined. Collagenolytic activity was determined by bioassay. Chondroprotective effects of IL4, IL13, transforming growth factor beta1 (TGFbeta1) and insulin-like growth factor-1 (IGF1) were assessed by inclusion in the explant cultures. RESULTS: IL17 alone stimulated a dose dependent release of proteoglycan and type II collagen from bovine nasal cartilage explants. Suboptimal doses of IL17 synergised potently with TNFalpha, IL1, OSM, and IL6 to promote collagen degradation. This collagen release was completely inhibited by tissue inhibitor of metalloproteinase-1 and BB-94 (a synthetic metalloproteinase inhibitor), and was significantly reduced by IL4, IL13, TGFbeta1, and IGF1. In IL17 treated chondrocytes, mRNA expression for matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 was detected. Moreover, a synergistic induction of these MMPs was seen when IL17 was combined with other proinflammatory cytokines. CONCLUSIONS: IL17 can, alone and synergistically in combination with other proinflammatory cytokines, promote chondrocyte mediated MMP dependent type II collagen release from cartilage. Because levels of all these proinflammatory cytokines are raised in rheumatoid synovial fluids, this study suggests that IL17 may act as a potent upstream mediator of cartilage collagen breakdown in inflammatory joint diseases.

The modulation of matrix metalloproteinase and ADAM gene expression in human chondrocytes by interleukin-1 and oncostatin M: a time-course study using real-time quantitative reverse transcription-polymerase chain reaction.

OBJECTIVE: Previous studies have reported elevated levels of interleukin-1 (IL-1) and oncostatin M (OSM) in rheumatoid joints, as well as the synergistic degradation of human articular cartilage by this cytokine combination. The present study was undertaken to investigate the ability of IL-1 and OSM to modulate gene expression of matrix metalloproteinase (MMP), ADAM, and ADAM-TS (ADAM with thrombospondin motifs) family members in human chondrocytes. METHODS: T/C28a4 human chondrocytes were stimulated for 2-48 hours with IL-1 and/or OSM. Total RNA was harvested, reverse transcribed, and assessed by real-time polymerase chain reaction for the expression of various MMP, ADAM, and ADAM-TS messenger RNAs (mRNA). Results were normalized to 18S ribosomal RNA. RESULTS: IL-1 and OSM synergized to markedly induce the expression of the collagenases MMP-1, MMP-8, and MMP-13 as well as MMP-3, an activator of proMMPs. Expression of mRNA for MMPs 1, 3, and 13 was induced early, whereas that of MMP-8 mRNA occurred late. Gene expression of MMP-14, an MMP that degrades collagen and activates proMMP-13, was elevated by this combination. IL-1 and OSM also synergized to induce gene expression of the aggrecanase ADAM-TS4, but not ADAM-TS5. CONCLUSION: These data indicate that the potent cartilage-degrading properties of the combination of IL-1 and OSM are potentially mediated by a synergistic induction of the aggrecan-degrading enzyme ADAM-TS4 and the collagen-degrading enzymes MMP-1, MMP-8, MMP-13, and MMP-14, although differences in the magnitude of response and in the time course of induction were observed. A role for MMPs 3 and 14 in the activation of proMMPs may also be implicated.

Synergistic induction of matrix metalloproteinase 1 by interleukin-1alpha and oncostatin M in human chondrocytes involves signal transducer and activator of transcription and activator protein 1 transcription factors via a novel mechanism.

OBJECTIVE: To investigate the mechanism of interleukin-1alpha (IL-1alpha) and oncostatin M (OSM) synergistic regulation of matrix metalloproteinase 1 (MMP-1) in human chondrocytes. METHODS: Using an immortalized human chondrocyte cell line (T/C28a4), we investigated regulation of the MMP-1 gene. Northern blotting and flow cytometric analysis were used to assess changes in receptor, MMP-1, and c-fos expression. Transient transfections using MMP-1 promoter/luciferase constructs, electrophoretic mobility shift assay, and site-directed mutagenesis were used to investigate MMP-1 promoter activation. RESULTS: We found no alteration in the expression of receptors used by these cytokines after stimulation with IL-1alpha/OSM. Using MMP-1 promoter/luciferase reporter constructs, we found that the proximal (-517/+63) region of the MMP-1 promoter was sufficient to support a synergistic activation. A role for activated signal transducers and activators of transcription (STAT-3) was demonstrated, although no binding of STAT-3 to the MMP-1 promoter was found. However, constitutive binding of activator protein 1 (AP-1) was detected, and changes in c-fos expression could modulate promoter activity. CONCLUSION: Since no changes in receptor expression were observed, receptor modulation cannot account for the IL-1alpha/OSM synergy observed. Instead, the interplay of various intracellular signaling pathways is a more likely explanation. STAT activation is required, but STAT proteins do not interact directly with the MMP-1 promoter. We propose that activated STATs stimulate c-fos expression, and changes in expression of the AP-1 components regulate MMP-1 expression. We highlight a new mechanism for MMP-1 regulation in human chondrocytes that could provide potential new therapeutic targets.

Synergistic effects of glycoprotein 130 binding cytokines in combination with interleukin-1 on cartilage collagen breakdown.

OBJECTIVE: To determine whether other glycoprotein 130 (gp130) binding cytokines can mimic the effects of oncostatin M (OSM) in acting synergistically with interleukin-1alpha (IL-1alpha) to induce cartilage collagen breakdown and collagenase expression, and to determine which receptors mediate these effects. METHODS: The release of collagen and proteoglycan was assessed in bovine and human cartilage explant cultures. Messenger RNA (mRNA) and protein production from immortalized human chondrocytes (T/C28a4) was analyzed by Northern blotting and specific enzyme-linked immunosorbent assays. Collagenase activity was measured by bioassay. Cell surface receptors were detected by flow cytometry. RESULTS: OSM in combination with IL-1alpha caused a rapid synergistic induction of matrix metalloproteinase 1 mRNA, which was sustained over a 72-hour period. Flow cytometric analyses detected both the OSM-specific receptor and the gp130 receptor at the chondrocyte cell surface, but failed to detect the leukemia inhibitory factor receptor (LIFR). Cartilage degradation assays revealed that, of the gp130 binding cytokines, only OSM and IL-6, in the presence of its soluble receptor (sIL-6R), were able to act synergistically with IL-1alpha to promote collagen release. CONCLUSION: This study demonstrates that IL-6 can mimic OSM in synergizing with IL-1alpha to induce chondrocyte-mediated cartilage collagen breakdown and collagenase production. In order to have this effect, IL-6 requires the presence of its soluble receptor. The apparent absence of LIFR explains why other gp130 binding cytokines do not act in synergy with IL-1alpha. Since OSM, IL-6, and sIL-6R levels have all been shown to be elevated in the rheumatoid joint, our findings suggest that these cytokines may be key mediators of cartilage collagen catabolism in the inflammatory arthritides.

Esculetin inhibits cartilage resorption induced by interleukin 1alpha in combination with oncostatin M.

OBJECTIVE: To determine if a new inhibitor, esculetin (EST), can block resorption of cartilage. METHODS: Interleukin 1alpha (IL1alpha, 0.04-5 ng/ml) and oncostatin M (OSM, 0.4-50 ng/ml) were used to stimulate the release of proteoglycan and collagen from bovine nasal cartilage and human articular cartilage in explant culture. Proteoglycan and collagen loss were assessed by dimethylmethylene blue and hydroxyproline assays, respectively. Collagenase levels were measured by assay of bioactivity and by enzyme linked immunosorbent assay (ELISA). The effects of EST on the expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the transformed human chondrocyte cell line T/C28a4 were assessed by northern blot analysis. TIMP-1 protein levels were assayed by ELISA. The effect of EST on the MMP-1 promoter was assessed using a promoter-luciferase construct in transient transfection studies. RESULTS: EST inhibited proteoglycan and collagen resorption in a dose dependent manner with significant decreases seen at 66 microM and 100 microM EST, respectively. Collagenolytic activity was significantly decreased in bovine nasal cartilage cultures. In human articular cartilage, EST also inhibited IL1alpha + OSM stimulated resorption and decreased MMP-1 levels. TIMP-1 levels were not altered compared with controls. In T/C28a4 chondrocytes the IL1alpha + OSM induced expression of MMP-1, MMP-3, and MMP-13 mRNA was reduced to control levels by 250 microM EST. TIMP-1 mRNA levels were unaffected by EST treatment. All cytokine stimulation of an MMP-1 luciferase-promoter construct was lost in the presence of the inhibitor. CONCLUSION: EST inhibits degradation of bovine nasal cartilage and human articular cartilage stimulated to resorb with IL1alpha + OSM.

96-Well plate assays for measuring collagenase activity using (3)H-acetylated collagen.

We describe two alternative assays for measuring collagenolytic activity using (3)H-acetylated collagen. Both assays have been developed for the 96-well plate format and measure the amount of radiolabeled collagen fragments released into the supernatant from an insoluble (3)H-acetylated collagen fibril preparation. The first method separates digested solubilized fragments from the intact fibril by sedimentation of the undigested collagen by centrifugation. The second method achieves this separation by filtration of the supernatant through the membrane of a 96-well filtration plate which retains the undigested collagen fibril. Both methods give linear dose- and time-dependent responses of collagenase activity > or = 70% of total collagen lysis. In addition, both assays can be simply modified to measure tissue inhibitors of metalloproteinases (TIMPs) inhibitory activity, which is also linear between 20 and 75% of total collagen lysis with the amount of TIMP added.