Experimental and Theoretical Insights into Interfacial Properties of 2D Materials for Selective Water Transport Membranes: A Critical Review.

Interfacial properties, such as wettability and friction, play critical roles in nanofluidics and desalination. Understanding the interfacial properties of two-dimensional (2D) materials is crucial in these applications due to the close interaction between liquids and the solid surface. The most important interfacial properties of a solid surface include the water contact angle, which quantifies the extent of interactions between the surface and water, and the water slip length, which determines how much faster water can flow on the surface beyond the predictions of continuum fluid mechanics. This Review seeks to elucidate the mechanism that governs the interfacial properties of diverse 2D materials, including transition metal dichalcogenides (e.g., MoS2), graphene, and hexagonal boron nitride (hBN). Our work consolidates existing experimental and computational insights into 2D material synthesis and modeling and explores their interfacial properties for desalination. We investigated the capabilities of density functional theory and molecular dynamics simulations in analyzing the interfacial properties of 2D materials. Specifically, we highlight how MD simulations have revolutionized our understanding of these properties, paving the way for their effective application in desalination. This Review of the synthesis and interfacial properties of 2D materials unlocks opportunities for further advancement and optimization in desalination.

Surface Roughness Explains the Observed Water Contact Angle and Slip Length on 2D Hexagonal Boron Nitride.

Hexagonal boron nitride (hBN) is a two-dimensional (2D) material that is currently being explored in a number of applications, such as atomically thin coatings, water desalination, and biological sensors. In many of these applications, the hBN surface comes into intimate contact with water. In this work, we investigate the wetting and frictional behavior of realistic 2D hBN surfaces with atomic-scale defects and roughness. We combine density functional theory calculations of the charge distribution inside hBN with free energy calculations using molecular dynamics simulations of the hBN-water interface. We find that the presence of surface roughness, but not that of vacancy defects, leads to remarkable agreement with the experimentally observed water contact angle of 66° on freshly synthesized, uncontaminated hBN. Not only that, the inclusion of surface roughness predicts with exceptional accuracy the experimental water slip length of ∼1 nm on hBN. Our results underscore the importance of considering realistic models of 2D materials with surface roughness while modeling nanomaterial-water interfaces in molecular simulations.

Biochemical analysis of leptospiral LPS explained the difference between pathogenic and non-pathogenic serogroups.

Lipopolysaccharide (LPS) is the major surface antigen of Leptospira. In this study, the genes involved in the LPS biosynthesis were analyzed and compared by bioinformatics tools. Also, the chemical composition analysis of leptospiral lipopolysaccharides (LPS) extracted from 5 pathogenic serovars like Autumnalis, Australis, Ballum, Grippotyphosa, Pomona, and the nonpathogenic serovar Andamana was performed. Methods used were Limulus amebocyte lysate assay (LAL), gas chromatography-mass spectrometry (GC-MS), fourier transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance spectroscopy (NMR). LAL assay showed a significantly higher level of endotoxicity among pathogenic serovars (~0.490 EU/mL) than that of nonpathogenic Andamana (~0.102 EU/mL). FAMES analysis showed the presence of palmitic acid (C16:0), hydroxy lauric acid (3-OH-C12:0), and oleic acid (C18:0). Palmitoleic acid (C16: 1), and 3- hydroxy palmitate (3-OH-C16:0) was detected only in pathogenic serovars. In contrast myristoleic acid (C14:1) and stearic acid (C18:0) were present in Andamana. FTIR analysis revealed C-O-C stretch of esters, 3°ROH functional groups and carbohydrate vibration range were similar among pathogenic serovars. The NMR analysis reveals similarity for 6 deoxy sugars and methyl groups of Autumnalis, Australis, and Ballum. Further, the presence of palmitoleic acid and 3-hydroxy palmitate may be the significant pathogen-associated predisposing factor. This mediates high osmolarity glycerol (HOG) mediated stress response in leptospiral LPS mediated pathogenesis.

Translation and validation of the Test of Adherence to Inhalers (TAI) questionnaire among adult patients with asthma in Malaysia.

OBJECTIVE: The Test of Adherence to Inhalers (TAI) is a validated self-reported questionnaire that can reliably assess adherence to inhalers through patient self-report. However, it was not available in Bahasa Melayu (BM) language, nor has it been validated for use in the Malaysian population. The study aimed, therefore, to translate the 10-item TAI questionnaire into BM and evaluate its psychometric properties. METHODS: The translation of the English version of the valid 10-item TAI questionnaire into BM was followed by subjecting it to a series of tests establishing factorial, concurrent and known group validities. Concurrent validity was assessed through Spearman's rank correlation coefficient against pharmacy refill-based adherence scores. Known group validity was assessed by cross-tabulation against asthma symptom control and using chi-square test. The internal consistency of the test scale was determined by a test-retest method using Cronbach's alpha (α) value and intraclass correlation coefficients. RESULTS: A total of 120 adult asthma patients participated in the study. A 2-factor structure was obtained and confirmed with acceptable fit indices; CFI, NFI, IFI, TLI >0.9 and, RMSEA was 0.08. The reliability of the scale was 0.871. The test-retest reliability coefficient for the total sum score was 0.832 (p < 0.01), which indicated good reliability. The 10-item TAI-BM established concurrent and known group validities. The sensitivity and specificity of the tool were >85%. CONCLUSIONS: The scale successfully translated into BM and validated. The 10-item TAI-BM appears fit for use in testing inhaler adherence of Malaysian patients with asthma.

Occurrence of potentially zoonotic and cephalosporin resistant enteric bacteria among shelter dogs in the Central and South-Central Appalachia.

BACKGROUND: Antimicrobial resistance and presence of zoonotic enteropathogens in shelter dogs pose a public health risk to shelter workers and potential adopters alike. In this study we investigated the prevalence of zoonotic bacterial pathogens and cephalosporin resistant (CefR) enteric bacteria in the feces of apparently healthy shelter dogs in the Cumberland Gap Region (CGR) in the US states of Kentucky, Tennessee and Virginia. RESULTS: Fecal samples of 59 dogs from 10 shelters in the CGR of Central and South-Central Appalachia were screened for the presence of Campylobacter jejuni, Clostridium perfringens, Salmonella and CefR enteric bacteria. C. jejuni, C. perfringens were detected by PCR based assays. Culture and PCR were used for Salmonella detection. Of 59 dogs, fecal samples from 14 (23.7%) and 8 (13.6%) dogs tested positive for cpa and hipO genes of C. perfringens and C. jejuni, respectively. Salmonella was not detected in any of the tested samples by PCR or culture. CefR enteric bacteria were isolated on MacConkey agar supplemented with ceftiofur followed by identification using MALDI-TOF. Fecal samples from 16 dogs (27.1%) yielded a total of 18 CefR enteric bacteria. Majority of CefR isolates (14/18, 77.8%) were E. coli followed by, one isolate each of Enterococcus hirae, Acinetobacter baumannii, Acinetobacter pittii, and Pseudomonas aeruginosa. CefR enteric bacteria were tested for resistance against 19- or 24-antibiotic panels using broth microdilution method. Seventeen (94.4%) CefR bacteria were resistant to more than one antimicrobial agent, and 14 (77.8%) displayed multidrug resistance (MDR). CONCLUSIONS: This study shows that shelter dogs within the CGR not only carry zoonotic bacterial pathogens, but also shed multidrug resistant enteric bacteria in their feces that may pose public health risks.

Serosurvey of arthropod-borne diseases among shelter dogs in the Cumberland Gap Region of the United States.

BACKGROUND: The Cumberland Gap Region (CGR) of the United States is a natural corridor between the southeastern, northeastern, and midwestern regions of the country. CGR has also many species of ticks and mosquitos that serve as competent vectors for important animal and human pathogens. In this study, we tested dogs from six different animal shelters in the CGR for Rocky Mountain spotted fever (RMSF), anaplasmosis, Lyme disease, canine ehrlichiosis and canine heartworm disease. RESULTS: Sera from 157 shelter dogs were tested for antibodies to RMSF agent, Rickettsia rickettsii, using an indirect immunofluorescence assay. Sixty-six dogs (42.0%) were positive for either IgM or IgG, or both IgM and IgG antibodies to R. rickettsii. Moreover, the same set of sera (n = 157) plus an and additional sera (n = 75) from resident dogs at the same shelters were tested using the SNAP 4Dx Plus. Of 232 dogs tested, two (0.9%) were positive for antibodies to Anaplasma phagocytophilum/A. platys, nine (3.9%) were positive for antibodies to Borrelia burgdorferi, 23 (9.9%) for positive for antibodies to Ehrlichia canis/E. ewingii, and 13 (5.6%) were positive for Dirofilaria immitis antigen. Co-infection with two or more etiologic agents was detected in five animals. Three dogs had antibodies to both B. burgdorferi and E. canis/E. ewingii, and two dogs were positive for D. immitis antigen and antibodies to B. burgdorferi and E. canis/E. ewingii. CONCLUSIONS: Shelter dogs in the CGR are exposed to a number of important vector-borne pathogens. Further studies are required to ascertain the roles these animals play in maintenance and transmission of these pathogens.

Evaluation of Antimicrobial Stewardship Programs (ASPs) and their perceived level of success at Makkah region hospitals, Kingdom of Saudi Arabia.

Antimicrobial stewardship programs (ASPs) are collaborative efforts to optimize antimicrobial use in healthcare institutions through evidence-based quality improvement strategies. The general administration of pharmaceutical care in the Saudi ministry of health (MOH) is putting outstanding efforts in implementing antimicrobial stewardship in Saudi health care settings. Several surveys have been conducted globally and reported many types of antimicrobial stewardship strategies in health institutions and their effectiveness. This study aims to identify ASPs in Makkah region hospitals and their perceived level of success. We administered a regional survey to explore current progress and issues related to the implementation of ASPs in Makkah region hospitals at the pharmacy level (n = 25). Among responding hospitals, 19 (76%) hospitals, the most commonly reported ASP were as following: formulary restrictions (90%) for broad-spectrum antimicrobials and use of prospective feedback on antimicrobial prescribing (68%), use of clinical guidelines and pathways (100%), and use of automatic stop orders (68%) to limit inappropriate antimicrobial therapy. The study outcomes will also be of pivotal importance to devise policies and strategies for antimicrobial stewardship implementation in other non-MOH settings in the Makkah region. Based on our results, all reported institutions have at least one antimicrobial stewardship program in a process with a high success rate. A multidisciplinary ASP approach, active involvement of drug & therapeutic committee, formulary restrictions, and availability of education & training of pharmacists and physicians on ASP are the primary elements for perceived successful antimicrobial stewardship programs in the Makkah region hospitals.

It is time to change the way we manage mild asthma: an update in GINA 2019.

Asthma is a heterogeneous lung disease, usually characterised by chronic airway inflammation. Although evidence-based treatments are available in most countries, asthma control remains suboptimal, and asthma-related deaths continue to be an ongoing concern. Generally, it is believed that between 50 to 75% of patients with asthma can be considered as having mild asthma.Previous versions of Global Initiative for Asthma (GINA) suggested that mild asthma in adults can be well managed with either reliever medications, for example, short-acting beta2 agonists (SABA) alone or with the additional use of controllers such as regular low-dose inhaled corticosteroids (ICS). Given the low frequency or non-bothersome nature of symptoms in mild asthma, patients' adherence towards their controller medications, especially to ICS is usually not satisfactory. Such patients often rely on SABA alone to relieve symptoms, which may contribute to SABA over-reliance. Overuse of relievers such as SABAs has been associated with poor asthma outcomes, such as exacerbations and even deaths. The new GINA 2019 asthma treatment recommendations represent significant shifts in asthma management at Steps 1 and 2 of the 5 treatment steps. The report acknowledges an emerging body of evidence suggesting the non-safety of SABAs overuse in the absence of concomitant controller medications, therefore does not support SABA-only therapy in mild asthma and has included new off-label recommendations such as symptom-driven (as-needed) low dose ICS-formoterol and "low dose ICS taken whenever SABA is taken".The GINA 2019 report highlights significant updates in mild asthma management and these recommendations represent a clear deviation from decades of clinical practice mandating the use of symptom-driven SABA treatment alone in those with mild asthma. While the new inclusions of strategies such as symptom-driven (as-needed) ICS-formoterol and "ICS taken whenever SABA is taken" are based on several key trials, data in this context are still only emergent data, with clear superiority of as needed ICS-formoterol combinations over maintenance ICS regimens yet to be established for valid endpoints. Nevertheless, current and emerging data position the clinical asthma realm at a watershed moment with imminent changes for the way we manage mild asthma likely in going forward.

Induction of Interleukin 10 by Borrelia burgdorferi Is Regulated by the Action of CD14-Dependent p38 Mitogen-Activated Protein Kinase and cAMP-Mediated Chromatin Remodeling.

Host genotype influences the severity of murine Lyme borreliosis, caused by the spirochetal bacterium Borrelia burgdorferi C57BL/6 (B6) mice develop mild Lyme arthritis, whereas C3H/HeN (C3H) mice develop severe Lyme arthritis. Differential expression of interleukin 10 (IL-10) has long been associated with mouse strain differences in Lyme pathogenesis; however, the underlying mechanism(s) of this genotype-specific IL-10 regulation remained elusive. Herein we reveal a cAMP-mediated mechanism of IL-10 regulation in B6 macrophages that is substantially diminished in C3H macrophages. Under cAMP and CD14-p38 mitogen-activated protein kinase (MAPK) signaling, B6 macrophages stimulated with B. burgdorferi produce increased amounts of IL-10 and decreased levels of arthritogenic cytokines, including tumor necrosis factor (TNF). cAMP relaxes chromatin, while p38 increases binding of the transcription factors signal transducer and activator of transcription 3 (STAT3) and specific protein 1 (SP1) to the IL-10 promoter, leading to increased IL-10 production in B6 bone marrow-derived monocytes (BMDMs). Conversely, macrophages derived from arthritis-susceptible C3H mice possess significantly less endogenous cAMP, produce less IL-10, and thus are ill equipped to mitigate the damaging consequences of B. burgdorferi-induced TNF. Intriguingly, an altered balance between anti-inflammatory and proinflammatory cytokines and CD14-dependent regulatory mechanisms also is operative in primary human peripheral blood-derived monocytes, providing potential insight into the clinical spectrum of human Lyme disease. In line with this notion, we have demonstrated that cAMP-enhancing drugs increase IL-10 production in myeloid cells, thus curtailing inflammation associated with murine Lyme borreliosis. Discovery of novel treatments or repurposing of FDA-approved cAMP-modulating medications may be a promising avenue for treatment of patients with adverse clinical outcomes, including certain post-Lyme complications, in whom dysregulated immune responses may play a role.

Role of Penile Doppler as a Diagnostic Tool in Penile Fracture.

Penile fracture is defined as a traumatic rupture of either corpus cavernosum or the tunica albuginea; sometimes it can be both. It may be caused by exotic masturbation acts, sexual intercourse, or other trauma to this area. This can be accompanied by injury to the urethra, which is the cause of hematuria as a symptom for some patients. Typically, diagnosis of penile rupture or fracture depends on clinical examination and history told by the patients. We are stating the importance of medical imaging in the diagnosis of patients with penile fracture by presenting a case of patient suffered from penile fracture after a fall on his penis where it affected the erection of two-third of his penis. In which, the proper diagnosis by imaging studies and taking actions accordingly can save the patients from unnecessary surgeries that indeed increase the bill of the medical care directly and indirectly. Therefore, most patients can be diagnosed cost-effectively and treated surgically without a need to delay surgery, which is often the case if one was to resort to other investigations. Investigations such as retrograde urethrography for suspected urethral injury should only be used when the diagnosis of penile fracture is in doubt.

Molecular characterization of Trichuris serrata.

Trichuris serrata, a whipworm of cats, can cause inflammation in the cecum and upper portion of the large intestine. It is unknown if the virulence and pathology of T. serrata differ from Trichuris campanula, the other species in cats. Distinguishing the species based on egg size is challenging. In addition, Trichuris eggs can be difficult to distinguish from Capillaria spp. This paper presents the first molecular description of T. serrata. The 18S ribosomal RNA (rRNA) gene was sequenced from male adult worms sourced from two unrelated cats on St. Kitts. Based on the analysis of 651 base pairs, T. serrata was found to be different than any other Trichuris species for which published sequencing of the 18S rRNA gene is available. A dendrogram was developed using Molecular Evolutionary Genetics Analysis version 6.0, and evolutionary history was inferred using the minimum evolution method. T. serrata was found to be most closely related to Trichuris vulpis, the Trichuris of dogs. Further development of the methodology could enable distinguishing T. serrata, T. campanula, and Capillaria spp. infections in cats and aid in diagnosis.

Densitometric method for assessment of six specialized metabolites in four Sida sp. and its congener Abutilon indicum: Targeted metabolomics, greenness assessment, and chemometrics analysis.

Sida is one of the most diverse genera, with about 200 species distributed in tropical and subtropical regions of the world. Among 18 species distributed in India, Sida acuta, Sida cordifolia, Sida rhombifolia, and Sida cordata are used in traditional medicines along with its possible adulterant Abutilon indicum for several therapeutic uses. The non-availability of marker-based validated methods for the identification and classification of these species leads to adulteration. Indoloquinoline and quinazoline are the major bioactive alkaloids distributed in Sida spp. First time, a simple, economical and high throughput method was developed and validated for the simultaneous determination of 20-hydroxyecdysone (1), vasicine (2), vasicinone (3), cryptolepine (4), quindolinone (5), and cryptolepinone (6) using HPTLC-UV densitometry. The method was validated to meet globally accepted ICH guidelines. The method was sensitive with LOD and LOQ ranging from 0.38-0.63 and 1.57-2.12 µg/band. The samples were spiked at 3 different concentrations, the recovery values were 93.49-98.88%. In addition, the greenness index of the HPTLC method was estimated using four different greenness assessment techniques. Targeted HPTLC analysis indicated the distribution of specialized metabolites in Sida spp. and A. indicum. However, the occurrence of cryptolepine in A. indicum was not reported in the literature, so this was further confirmed by liquid chromatographic studies of the samples from different locations. The chromatographic data was statistically evaluated by principal component analysis (PCA) and hierarchical clustering (HCA). HPTLC-based targeted metabolite quantitation explains the adulteration/substitution in Sida raw material and derived herbal preparations.

Posttranscriptional self-regulation by the Lyme disease bacterium's BpuR DNA/RNA-binding protein.

Bacteria require explicit control over their proteomes in order to compete and survive in dynamic environments. The Lyme disease spirochete Borrelia burgdorferi undergoes substantial protein profile changes during its cycling between vector ticks and vertebrate hosts. In an effort to understand regulation of these transitions, we recently isolated and functionally characterized the borrelial nucleic acid-binding protein BpuR, a PUR domain-containing protein. We now report that this regulatory protein governs its own synthesis through direct interactions with bpuR mRNA. In vitro and in vivo techniques indicate that BpuR binds with high affinity and specificity to the 5' region of its message, thereby inhibiting translation. This negative feedback could permit the bacteria to fine-tune cellular BpuR concentrations. These data add to the understanding of this newly described class of prokaryotic DNA- and RNA-binding regulatory proteins.

C-H Bond Functionalization of Aryl Acids and Amines by 'On-water' Reaction: Bi-dentate Directing Group Enabled Synthesis of Biaryl and m-Teraryl Carboxamides.

Herein, we report a palladium-catalyzed 'on-water' methodology for the synthesis of biaryl and m-teraryl derivatives of aryl carboxamides by selective mono and bis C-H bond functionalization. 8-aminoquinoline and 2-thiomethylaniline were used as directing groups for C-H bond functionalization of aryl carboxamides with various aryl and alkyl iodides using 3.0-4.0 mol% of Pd(OAc)2 as catalyst and water as the solvent resulting in 45-97% isolated yields of the mono and bis C-H bond functionalized products. Using an 8-aminoquinoline carboxamide core, C-H bond functionalization of indole-3-carboxylic acid and a late-stage functionalization of aspirin molecule have also been carried out. Reactions of benzyl/naphthyl picolinamides with aryl iodides gave 60-96% yield of the arylated products using the picolinamide directing group. Moreover, the insoluble nature of products in an aqueous medium enabled us to explore the reusability of the solvent, i. e., water and the catalyst. Control experiments and structural studies were carried out which confirmed the in situ formation of unique palladacycles during the reaction. Removal of the directing groups has been carried out to convert the functionalized products into amines and fluorenone compounds useful in industrial and pharmaceutical applications.

Stimulation of glucose uptake by glycosides from Alectra parasitica subsp. chitrakutensis (M.A. Rau) K.K. Khanna & An. Kumar: An in-vitro study of TNF-α induced insulin resistance in L6 myoblasts.

Alectra parasitica subsp. chitrakutensis (M.A. Rau) K.K. Khanna & An. Kumar (Orobanchaceae) is a parasitic plant indigenous to India. Locally, the plant is known as 'Midaki and Nirgundikand'. It is used to treat fever, piles, cardiovascular disorders, and blood-borne non-infectious diseases by ethnic communities. The phytochemical investigation of A. parasitica subsp. chitrakutensis rhizome led to the isolation of azafrin (1), rehmaionoside-C (2), and mussaenoside (3). Compounds (2) and (3) are being reported for the first time from this plant. Compounds were evaluated for their intercellular glucose uptake activity in basal and insulin-TNF-α-stimulated L6 muscle cells. In particular, rehmaionoside C exhibited activity comparative to metformin, increasing uptake by basal- and insulin-TNF-α-stimulated cells by 4.88- and 3.90-fold and 5.04- and 4.04-fold. While azafrin and mussaenoside have produced 3.03- and 2.36-fold; 4.03- and 3.22-fold increase in intercellular glucose uptake. Compounds did not show toxicities in rat L6 myoblast cells. The study suggests that rehmaionoside-C from A. parasitica subsp. chitrakutensis might activate glucose uptake by insulin mimics and could be a nontoxic anti-diabetes lead for drug discovery.

A Bench-stable 8-Aminoquinoline Derived Phosphine-free Manganese (I)-Catalyst for Environmentally Benign C(α)-Alkylation of Oxindoles with Secondary and Primary Alcohols.

Herein, we report a new air-stable phosphine-free 8-AQ (8-aminoquinoline) based Mn(I) carbonyl complex as the catalyst for the C(α)-alkylation of oxindoles with alcohols. The Mn complex [(8-AQ)Mn(CO)3 Br] works effectively as a catalyst for the α-alkylation of oxindoles by both secondary as well as primary alcohols. The procedure has been used for the synthesis of pharmaceutically important recently developed oxindoles such as 3-(4-methoxybenzyl)indolin-2-one, 3-(4-(dimethylamino)benzyl)indolin-2-one, 3-(4-(dimethylamino)phenyl)-5-fluoroindolin-2-one and 3-(benzo[d][1,3]dioxol-5-ylmethyl)indolin-2-one, which are found to be effective in preventing specific types of cell death in neurodegenerative disorders. Control experiments have been carried out to investigate the reaction mechanism and the crucial role of metal-ligand cooperation via -NH2 moiety during catalysis.

Reduction of esters to alcohols and iodides using aminodiborane (µ-NH2B2H5): scope and mechanistic investigations.

Herein, we report an efficient methodology for the reduction of esters, carbonates, and anhydrides to alcohols using in situ generated aminodiborane from iodine and ammonia borane. This methodology also finds use for the transformation of esters to iodides by varying the stoichiometry of reagents. The protocol has broad substrate scope for transformation of esters to alcohols and iodides with excellent yields. The method is also useful for synthesizing pharmaceutically and industrially important compounds such as a Cinacalcet precursor, a Streptoindole analogue, and 1,4-pentanediol. Control studies and DFT calculations carried out to study the reduction mechanism of esters using aminodiborane indicate that a dioxaborinamine intermediate is formed during the reaction.

Protrusio acetabuli in tubercular hip: Outcome of femoral head as autologous bone graft used during total hip replacement.

Purpose: Here we present a study of a tuberculosis hip protrusion with a large acetabular defect treated by total hip replacement using a novel technique without the use of any protrusio ring, wire mesh, or cage. To our knowledge, such a technique has not been described in the literature previously. Methodology: 25 patients with a past treatment history of hip tuberculosis came to our medical college with complaints of worsening pain in the hip joint and limping. The hip pain and limping were progressive in nature and became more severe, and his affected lower limb shortened. Results: The average AK distance (horizontal distance between Kohlar line and the medial acetabular border) before surgery was 8 mm (range: 1-16). For the acetabular implant, the mean abduction angle was 45° (range: 41-48), and the mean anteversion angle was 18° (range: 13-24). The average preoperative shortening for limb length inequality was 4 mm (range: 0-11). The average HHS (Harris Hip Score) during follow-up was 87.6 points. Conclusion: In TB hip protrusio, an autograft of the femur head is used to fill the acetabular defect and provide a good approach for these patients without any extra economic burden or complications as seen in a metallic ring or cage.