Functional diversity among cardiolipin binding sites on the mitochondrial ADP/ATP carrier.

Lipid-protein interactions play a multitude of essential roles in membrane homeostasis. Mitochondrial membranes have a unique lipid-protein environment that ensures bioenergetic efficiency. Cardiolipin (CL), the signature mitochondrial lipid, plays multiple roles in promoting oxidative phosphorylation (OXPHOS). In the inner mitochondrial membrane, the ADP/ATP carrier (AAC in yeast; adenine nucleotide translocator, ANT in mammals) exchanges ADP and ATP, enabling OXPHOS. AAC/ANT contains three tightly bound CLs, and these interactions are evolutionarily conserved. Here, we investigated the role of these buried CLs in AAC/ANT using a combination of biochemical approaches, native mass spectrometry, and molecular dynamics simulations. We introduced negatively charged mutations into each CL-binding site of yeast Aac2 and established experimentally that the mutations disrupted the CL interactions. While all mutations destabilized Aac2 tertiary structure, transport activity was impaired in a binding site-specific manner. Additionally, we determined that a disease-associated missense mutation in one CL-binding site in human ANT1 compromised its structure and transport activity, resulting in OXPHOS defects. Our findings highlight the conserved significance of CL in AAC/ANT structure and function, directly tied to specific lipid-protein interactions.

Efficacy of peribulbar bupivacaine at the end of surgery in the management of postoperative pain after scleral buckling.

PURPOSE: To compare the efficacy of peribulbar bupivacaine with routine analgesics for pain management in patients undergoing scleral buckling. METHODS: In total, 72 patients undergoing scleral buckling or combined with vitrectomy were enrolled in this study. Patients were randomized into two groups, each containing 36 patients. Patients of group A received 5 mL of bupivacaine (0.5%) injection at the end of surgery, whereas group B patients received routine analgesics. The postoperative pain score was assessed in the first 24 hours of the postoperative period with the visual pain analog score. RESULTS: Maximum postoperative pain scores were lower in patients receiving bupivacaine block (median: 3; range: 3-7) than in the control group (median: 5; range: 3-9). Pain scores in group A were lower than in the control group both at 3 and 6 hours after surgery, which was statistically significant ( P < 0.001). Four patients in group A and 17 patients in group B needed additional analgesia in the first 24 hours of the postoperative period. In addition, two patients in group A and seven patients in group B experienced episodes of nausea and vomiting in the first 24 hours of surgery. CONCLUSION: The results of this study suggest that the postoperative experience of patients undergoing scleral buckling surgery can be made more comfortable with the use of bupivacaine block at the end of surgery.

Intrabony defect management with a bone graft (hydroxyapatite and ß-tricalcium phosphate) alone and in combination with a diode laser: A randomized control trial.

Objectives: The current research was conducted to evaluate the use of a diode laser and a bone graft (hydroxyapatite [HA] + ß-tricalcium phosphate [ß-TCP]) in healing of intrabony defects. Materials and Methods: In this split-mouth evaluation, 40 patients with bilateral intrabony defects were treated with, Group I (control) - bone graft alone (HA + ß-TCP) and Group II, (test) - bone graft with a diode laser. The clinical and radiologic parameters of all patients, such as plaque index (PI), probing depth (PD), gingival index (GI), gingival recession (GR), and relative clinical attachment level (RCAL) were recorded at baseline, after 3 months and after 6 months. Results: Reductions in PI, PD, GI, GR, and RCAL were found after 6 months. Furthermore, significant differences were displayed in the intra-group comparison while those of the inter-group evaluation (P > 0.05) were insignificant. Conclusion: In both groups, considerable decrease in intrabony pockets was discovered; however, the inter-group comparison was insignificant in relation to GR and RCAL.

Finite element analysis to assess stress and deformation in bone with glass fiber-reinforced-poly-ether-ether-ketone, zirconia, and titanium implants.

Objectives: Recently, zirconia ceramic and glass or carbon fiber-reinforced poly-ether-ether-ketone (PEEK) composites have been introduced as newer implant biomaterials. This study was done to evaluate stress and deformation in bone with glass fiber-reinforced (GFR)-PEEK, zirconia, and titanium implants. Materials and Methods: A geometric model of mandibular molar replaced with implant-supported crown was generated. Implant of 12 mm length and 4.5 mm diameter was used in study. Finite element analysis models of implant assemblies of three materials GFR-PEEK, zirconium, and titanium were generated. 150 N loads were applied obliquely and vertically along the long axis of implant. Von Mises stresses and deformation generated were compared using ANSYS Workbench 17.0 and finite element software. Results: All three implant assemblies, i.e., GFR-PEEK, zirconia, and titanium, demonstrated similar stresses and deformation in bone without significant difference. Conclusion: It was concluded that GFR-PEEK and zirconia implants can be used as a substitute to titanium implants.

Conserved cardiolipin-mitochondrial ADP/ATP carrier interactions assume distinct structural and functional roles that are clinically relevant.

The mitochondrial phospholipid cardiolipin (CL) promotes bioenergetics via oxidative phosphorylation (OXPHOS). Three tightly bound CLs are evolutionarily conserved in the ADP/ATP carrier (AAC in yeast; adenine nucleotide translocator, ANT in mammals) which resides in the inner mitochondrial membrane and exchanges ADP and ATP to enable OXPHOS. Here, we investigated the role of these buried CLs in the carrier using yeast Aac2 as a model. We introduced negatively charged mutations into each CL-binding site of Aac2 to disrupt the CL interactions via electrostatic repulsion. While all mutations disturbing the CL-protein interaction destabilized Aac2 monomeric structure, transport activity was impaired in a pocket-specific manner. Finally, we determined that a disease-associated missense mutation in one CL-binding site in ANT1 compromised its structure and transport activity, resulting in OXPHOS defects. Our findings highlight the conserved significance of CL in AAC/ANT structure and function, directly tied to specific lipid-protein interactions.

The Evaluation of the Antibacterial and Antifungal Efficacy of Novel Kids Mineral Trioxide Aggregate (e-MTA) With ProRoot MTA and Glass Ionomer Cement.

Background Most pulpal and periapical problems could be treated nonsurgically. However, in cases of infections, certain operations must be performed that require using materials with good antibacterial and antifungal efficacy. ProRoot mineral trioxide aggregate (MTA) was marketed as gray- and white-colored preparations, composed of 75% Portland cement, 20% bismuth oxide, and 5% gypsum by weight. MTA, composed of powder and liquid as distilled water, formed a colloidal gel that further solidified and formed a hard cement within approximately four hours. The new endodontic material Kids e-MTA (Kids-e-dental, Mumbai, India) was introduced recently. It was also available as powder and liquid. It was a bioactive cement consisting of very fine hydrophilic particles of several mineral oxides. Aim This study compares the antimicrobial and antifungal efficacy of e-MTA (mineral trioxide aggregate) (Kids-e-dental, Mumbai, India), ProRoot MTA (Dentsply Sirona, Tulsa Dental, OK, USA), and glass ionomer cement (GIC) (GC Asia Dental Pte Ltd, Singapore). Materials and methods The agar diffusion method was used to test the materials. e-MTA, ProRoot MTA, and GIC were tested for their antibacterial efficacy against Enterococcus faecalis and antifungal efficacy against Candida albicans. The zone of inhibition was calculated and measured using a precision ruler. The collected data was put through Student's unpaired t-test. Results and conclusions On conducting the tests and comparing the results, it was found that e-MTA had a slightly better antibacterial efficacy and almost similar antifungal efficacy compared to ProRoot MTA but significantly superior properties compared to GIC.

Diabetic Retinopathy Screening Using Smartphone-Based Fundus Imaging in India.

PURPOSE: Early detection and treatment can prevent irreversible blindness from diabetic retinopathy (DR), which is the leading cause of visual impairment among working-aged adults worldwide. Some 80% of affected persons live in low- and middle-income countries, yet lack of resources has largely prevented DR screening implementation in these world regions. Smartphone-based fundus imaging (SBFI) allows for low-cost mobile fundus examination using an adapter on a smartphone; however, key aspects such as image quality, diagnostic accuracy, and comparability of different approaches have not been systematically assessed to date. DESIGN: Evaluation of diagnostic technology. PARTICIPANTS: A total of 381 eyes of 193 patients with diabetes were recruited at outreach eye clinics in South India. METHODS: We compared 4 technically different approaches of SBFI (3 approaches based on direct and 1 approach based on indirect ophthalmoscopy) in terms of image quality and diagnostic accuracy for DR screening. MAIN OUTCOME MEASURES: Image quality (sharpness/focus, reflex artifacts, contrast, and illumination), field-of-view, examination time, and diagnostic accuracy for DR screening were analyzed against conventional fundus photography and clinical examination. RESULTS: Smartphone-based fundus imaging based on indirect ophthalmoscopy yielded the best image quality (P < 0.01), the largest field-of-view, and the longest examination time (111 vs. 68-86 seconds, P < 0.0001). Agreement with the reference standard (Cohen's kappa 0.868) and sensitivity/specificity to detect DR were highest for the indirect SBFI approach (0.79/0.99 for any DR and 1.0/1.0 for severe DR, 0.79/1.0 for diabetic maculopathy). CONCLUSIONS: Smartphone-based fundus imaging can meet DR screening requirements in an outreach setting; however, not all devices are suitable in terms of image quality and diagnostic accuracy. Smartphone-based fundus imaging might aid in alleviating the burden of DR screening in low- and middle-income countries, and these results will allow for a better selection of SBFI devices in field trials for DR screening.

Recurrent unintentional filtering blebs after vitrectomy: A case report.

A lady who underwent lensectomy for microspherophakia and pars plana vitrectomy for retinal detachment in her left eye developed recurrent filtering blebs at the site of sclerotomies. Filtering blebs were managed by suturing the sclerotomies. Targeted gene sequencing identified a variant of ASPH gene (p.Arg688Gln) which is not known to be associated with Traboulsi syndrome. But considering the paucity of cases with genetic analysis, it would be possible that p.Arg688Gln is a pathogenic variant. This is the first case report of Traboulsi syndrome due to an ASPH variant not reported earlier that can lead to recurrent filtering blebs.

Vitrectomy as a treatment modality in vitreous seeding secondary to ciliary body melanocytoma.

Melanocytoma is a locally invasive intraocular tumor usually located in the optic nerve head, iris, ciliary body and choroid. Melanocytoma can undergo necrosis and lead to pigment dispersion. We report a case of melanocytoma of the ciliary body with vitreous seeds filling the vitreous cavity. A sub conjunctival pigmented lesion was seen due to extra scleral extension of the tumor. The diagnosis of melanocytoma was confirmed by biopsy of the sub conjunctival lesion. Pars plana vitrectomy was performed to clear the vitreous cavity with good visual recovery.

Optical coherence tomography angiography in assessment of response to therapy in retinal capillary hemangioblastoma and diffuse choroidal hemangioma.

In this series, we discuss the role of optical coherence tomography angiography (OCTA) in assessing response to treatment in intraocular vascular tumors. This is a series of two cases: Multiple retinal capillary hemangioblastoma (RCH) treated with laser photocoagulation and diffuse choroidal hemangioma (DCH) with radiotherapy. In large RCH and DCH, optical coherence tomography (OCT) showed significant reduction of subretinal and intraretinal fluid. But post-treatment mean tumor vascular density (MTVD) was slightly reduced. In one small RCH, vascular loop was seen suggesting minimal residual disease. So, OCTA helps in identifying treatment inadequacy and understanding alternate mechanism involved in treatment response in vascular tumors.

Scanning electron microscopic study of teeth restored with fiber posts and composite resin: An in vitro study.

AIMS AND OBJECTIVES: The aim of this study is to compare and evaluate the thickness of resin dentin interface zones (RDIZ) obtained by luting carbon fiber post to intra-radicular dentin, either with All-Bond 2 bonding agent and C and B composite cement or Panavia F dentin-bonding system and Panavia F resin cement. MATERIALS AND METHODS: Twenty single rooted mandibular premolars of similar sizes were prepared for the carbon fiber post after biomechanical preparation and obturation. They were divided into two groups, Group 1 and 2 of 10 samples each. Carbon fiber posts used for Group 1 samples were luted using All-Bond 2 and C and B cement. For Group 2 carbon fiber posts were luted using Panavia F dentin-bonding system and Panavia F resin cement. All the 20 samples were sectioned longitudinally and marked at three points on the length of the tooth from the dentin-core interface to the apex at 2 mm, 5 mm, and 8 mm to get coronal, middle, and apical areas, respectively. The formation and thickness (width) of the RDIZ at the marked areas was evaluated by scanning electron microscope using ×1000 magnification. The results were statistical analyzed. RESULTS: Irrespective of the adhesive systems used all specimens showed a RDIZ formation. Microscopic examination of Group 1 showed significantly higher percentage of RDIZ (P < 0.05) than Group 2. RDIZ morphology was easily detectable at coronal and middle areas of all specimens. CONCLUSION: All-Bond 2 showed denser and wider RDIZ compared with the Panavia F.

The acceptance of hearing disability among adults experiencing hearing difficulties: a cross-sectional study.

OBJECTIVE: This study developed the Hearing Disability Acceptance Questionnaire (HDAQ) and tested its construct and concurrent validities. DESIGN: Cross-sectional. PARTICIPANTS: A total of 90 participants who were experiencing hearing difficulties were recruited in the UK. OUTCOME MEASURES: The HDAQ was developed based on the Tinnitus Acceptance Questionnaire (TAQ). Participants completed self-report measures regarding hearing disability acceptance, hearing disability, symptoms of anxiety and depression and a measure of stages of change. RESULTS: The HDAQ has a two-factor structure that explains 75.69% of its variance. The factors identified were activity engagement and avoidance and suppression. The scale showed a sufficient internal consistency (Cronbach's α=0.86). The HDAQ also had acceptable concurrent validity with regard to self-reported hearing disability, self-reported anxiety and depression and readiness to change measures. CONCLUSIONS: Acceptance is likely an important aspect of coping with chronic health conditions. To our knowledge, no previously published and validated scale measures the acceptance of hearing disability; therefore, the HDAQ might be useful in future research. However, the role of acceptance in adjusting to hearing disability must be further investigated.

Communication Partners' Journey through Their Partner's Hearing Impairment.

The objective of this study was to further develop the Ida Institute model on communication partners' (CPs) journey through experiences of person with hearing impairment (PHI), based on the perspectives of CPs. Nine CPs of hearing aid users participated in this study, recruited through the Swansea hearing impaired support group. Semi-structured interviews were conducted, the data were analysed using qualitative thematic analysis and presented with the use of process mapping approach. Seven main phases were identified in the CP journey which includes: (1) contemplation, (2) awareness, (3) persuasion, (4) validation, (5) rehabilitation, (6) adaptation, and (7) resolution. The Ida Institute model (based on professionals' perspective) was compared with the new template developed (based on CPs' perspectives). The results suggest some commonalities and differences between the views of professionals and CPs. A new phase, adaptation, was identified from CPs reported experiences, which was not identified by professionals in the Ida Institute model. The CP's journey model could be a useful tool during audiological enablement/rehabilitation sessions to promote discussion between the PHI and the CP. In addition, it can be used in the training of hearing healthcare professionals.

Use of the 'patient journey' model in the internet-based pre-fitting counseling of a person with hearing disability: study protocol for a randomized controlled trial.

BACKGROUND: Hearing impairment is one of the most frequent chronic conditions. Persons with a hearing impairment (PHI) have various experiences during their 'journey' through hearing loss. In our previous studies we have developed a 'patient journey' model of PHI and their communication partners (CPs). We suggest this model could be useful in internet-based pre-fitting counseling of a person with hearing disability (PHD). METHODS/DESIGN: A randomized controlled trial (RCT) with waiting list control (WLC) design will be used in this study. One hundred and fifty eight participants with self-reported hearing disability (that is, score > 20 in the Hearing Handicap Questionnaire (HHQ)) will be recruited to participate in this study. They will be assigned to one of two groups (79 participants in each group): (1) Information and counseling provision using the 'patient journey' model; and (2) WLC. They will participate in a 30 day (4 weeks) internet-based counseling program based on the 'patient journey' model. Various outcome measures which focuses on hearing disability, depression and anxiety, readiness to change and acceptance of hearing disability will be administered pre (one week before) and post (one week and six months after) intervention to evaluate the effectiveness of counseling. DISCUSSION: Internet-based counseling is being introduced as a viable option for audiological rehabilitation. We predict that the 'patient journey' model will have several advantages during counseling of a PHD. Such a program, if proven effective, could yield cost and time-efficient ways of managing hearing disability. TRIAL REGISTRATION: ClinicalTrials.gov Protocol Registration System NCT01611129.

Parental reported benefits and shortcomings of cochlear implantation: Pilot study findings from Southeast Asia.

OBJECTIVE: The aim of the study was to understand the reported benefits and shortcomings by parents of children with cochlear implants and who contribute towards the cost of the implant. METHOD: Thirty parents of children with cochlear implants from a hearing impaired school in Southeast Asia completed open-ended questionnaires and the data were analysed using content analysis. RESULTS: A wide range of benefits and shortcomings were reported. However, it is notable that the single most reported shortcoming was related to cost. DISCUSSION: The results suggest that, even though, in general, the reports about benefits and shortcomings were similar to previous results from western countries, the emphasis given to various aspects of shortcomings was different. In particular, it appears that parentally reported outcomes could be related to many factors including the hearing healthcare system with the costs involved for the implanted individuals and their families. These findings help us understand the parental perspectives of the success of cochlear implantation and will be useful during parental counselling sessions.

Audiological practice in India: an internet-based survey of audiologists.

The field of Audiology in India has expanded exponentially in recent years. Audiologists practice in a variety of work places. However, little is known about the practice trends across these several work places. An Internet-based survey probing into Audiology practice was conducted between June and September 2012. The survey focused on four domains, namely, demography, assessment, hearing aid (HA) fitting and protocol usage. A total of 199 audiologists completed the survey. A large proportion of these audiologists were from Southern India. Majority of the respondents provide hearing assessment and HA services for children and adults. Results indicate diverse practice among respondents, even in essential procedures such as otoscopy. Although a large proportion of audiologists reported performing HA fitting in children as well as adults, less than 12 % of them performed real ear or simulated real ear verification during any HA fitting. Implications for the development of preferred practice guidelines in India have been discussed.