Reconstruction of Maxillary Defects Using Virtual Surgical Planning and Additive Manufacturing Technology: A Tertiary Care Centre Experience.

Introduction: Maxillary reconstruction is often a challenging task for the surgeons because of the complex anatomy. However, with the advances in virtual surgical planning (VSP) and 3D printing technology there is a new avenue for the surgeons which offers a suitable alternative to conventional flap-based reconstructions. Patients and Methods: In this article, we have described 4 case scenarios which were managed with the help of VSP and additive manufacturing technology for complex maxillary reconstruction procedures. Use of the technologies aided the clinician in achieving optimal outcomes with regards to form, function and esthetics. Discussion: Virtual surgical planning (VSP) has gained a lot of impetus in past 1 decade. These aides the surgeon in determining the extent of disease and also carry out the treatment planning. In addition to VSP, the concept of additive manufacturing provides a viable alternative to the conventional reconstruction modalities for maxillary defect rehabilitation. Increased accuracy, rehabilitation of normal anatomical configuration, appropriate dental rehabilitation, decreased intra-operative time and post-operative complications are some of the advantages. In addition, patient-specific implants eliminate the need for a separate donor site. Apart from the treatment of pathologies, they also can be used for reconstruction of post-traumatic defect, where endosteal implant placement is not possible. Conclusion: These modalities show promising results for reconstruction of complex maxillary defects.

CHSI costing study-Challenges and solutions for cost data collection in private hospitals in India.

INTRODUCTION: Ayushman Bharat Pradhan Mantri Jan Aarogya Yojana (AB PM-JAY) has enabled the Government of India to become a strategic purchaser of health care services from private providers. To generate base cost evidence for evidence-based policymaking the Costing of Health Services in India (CHSI) study was commissioned in 2018 for the price setting of health benefit packages. This paper reports the findings of a process evaluation of the cost data collection in the private hospitals. METHODS: The process evaluation of health system costing in private hospitals was an exploratory survey with mixed methods (quantitative and qualitative). We used three approaches-an online survey using a semi-structured questionnaire, in-depth interviews, and a review of monitoring data. The process of data collection was assessed in terms of time taken for different aspects, resources used, level and nature of difficulty encountered, challenges and solutions. RESULTS: The mean time taken for data collection in a private hospital was 9.31 (± 1.0) person months including time for obtaining permissions, actual data collection and entry, and addressing queries for data completeness and quality. The longest time was taken to collect data on human resources (30%), while it took the least time for collecting information on building and space (5%). On a scale of 1 (lowest) to 10 (highest) difficulty levels, the data on human resources was the most difficult to collect. This included data on salaries (8), time allocation (5.5) and leaves (5). DISCUSSION: Cost data from private hospitals is crucial for mixed health systems. Developing formal mechanisms of cost accounting data and data sharing as pre-requisites for empanelment under a national insurance scheme can significantly ease the process of cost data collection.

Cost of Surgical Care at Public Sector District Hospitals in India: Implications for Universal Health Coverage and Publicly Financed Health Insurance Schemes.

BACKGROUND: In low- and middle-income countries (LMICs), provisioning for surgical care is a public health priority. Ayushman Bharat Pradhan Mantri-Jan Aarogya Yojana (AB PM-JAY) is India's largest national insurance scheme providing free surgical and medical care. In this paper, we present the costs of surgical health benefit packages (HBPs) for secondary care in public district hospitals. METHODS: The costs were estimated using mixed (top-down and bottom-up) micro-costing methods. In phase II of the Costing of Health Services in India (CHSI) study, data were collected from a sample of 27 district hospitals from nine states of India. The district hospitals were selected using stratified random sampling based on the district's composite development score. We estimated unit costs for individual services-outpatient (OP) visit, per bed-day in inpatient (IP) and intensive care unit (ICU) stays, and surgical procedures. Together, this was used to estimate the cost of 250 AB PM-JAY HBPs. RESULTS: At the current level of utilization, the mean cost per OP consultation varied from US$4.10 to US$2.60 among different surgical specialities. The mean unit cost per IP bed-day ranged from US$13.40 to US$35.60. For the ICU, the mean unit cost per bed-day was US$74. Further, the unit cost of HBPs varied from US$564 for bone tumour excision to US$49 for lid tear repair. CONCLUSIONS: Data on the cost of delivering surgical care at the level of district hospitals is of critical value for evidence-based policymaking, price-setting for surgical care and planning to strengthen the availability of high quality and cost-effective surgical care in district hospitals.

A nomogram-based diabetic sensorimotor polyneuropathy severity prediction using Michigan neuropathy screening instrumentations.

BACKGROUND: Diabetic Sensorimotor polyneuropathy (DSPN) is one of the major indelible complications in diabetic patients. Michigan neuropathy screening instrumentation (MNSI) is one of the most common screening techniques used for DSPN, however, it does not provide any direct severity grading system. METHOD: For designing and modeling the DSPN severity grading systems for MNSI, 19 years of data from Epidemiology of Diabetes Interventions and Complications (EDIC) clinical trials were used. Different Machine learning-based feature ranking techniques were investigated to identify the important MNSI features associated with DSPN diagnosis. A multivariable logistic regression-based nomogram was generated and validated for DSPN severity grading using the best performing top-ranked MNSI features. RESULTS: Top-10 ranked features from MNSI features: Appearance of Feet (R), Ankle Reflexes (R), Vibration perception (L), Vibration perception (R), Appearance of Feet (L), 10-gm filament (L), Ankle Reflexes (L), 10-gm filament (R), Bed Cover Touch, and Ulceration (R) were identified as important features for identifying DSPN by Multi-Tree Extreme Gradient Boost model. The nomogram-based prediction model exhibited an accuracy of 97.95% and 98.84% for the EDIC test set and an independent test set, respectively. A DSPN severity score technique was generated for MNSI from the DSPN severity prediction model. DSPN patients were stratified into four severity levels: absent, mild, moderate, and severe using the cut-off values of 17.6, 19.1, 20.5 for the DSPN probability less than 50%, 75%-90%, and above 90%, respectively. CONCLUSIONS: The findings of this work provide a machine learning-based MNSI severity grading system which has the potential to be used as a secondary decision support system by health professionals in clinical applications and large clinical trials to identify high-risk DSPN patients.

ABCB10 exports mitochondrial biliverdin, driving metabolic maladaptation in obesity.

Although the role of hydrophilic antioxidants in the development of hepatic insulin resistance and nonalcoholic fatty liver disease has been well studied, the role of lipophilic antioxidants remains poorly characterized. A known lipophilic hydrogen peroxide scavenger is bilirubin, which can be oxidized to biliverdin and then reduced back to bilirubin by cytosolic biliverdin reductase. Oxidation of bilirubin to biliverdin inside mitochondria must be followed by the export of biliverdin to the cytosol, where biliverdin is reduced back to bilirubin. Thus, the putative mitochondrial exporter of biliverdin is expected to be a major determinant of bilirubin regeneration and intracellular hydrogen peroxide scavenging. Here, we identified ABCB10 as a mitochondrial biliverdin exporter. ABCB10 reconstituted into liposomes transported biliverdin, and ABCB10 deletion caused accumulation of biliverdin inside mitochondria. Obesity with insulin resistance up-regulated hepatic ABCB10 expression in mice and elevated cytosolic and mitochondrial bilirubin content in an ABCB10-dependent manner. Revealing a maladaptive role of ABCB10-driven bilirubin synthesis, hepatic ABCB10 deletion protected diet-induced obese mice from steatosis and hyperglycemia, improving insulin-mediated suppression of glucose production and decreasing lipogenic SREBP-1c expression. Protection was concurrent with enhanced mitochondrial function and increased inactivation of PTP1B, a phosphatase disrupting insulin signaling and elevating SREBP-1c expression. Restoration of cellular bilirubin content in ABCB10 KO hepatocytes reversed the improvements in mitochondrial function and PTP1B inactivation, demonstrating that bilirubin was the maladaptive effector linked to ABCB10 function. Thus, we identified a fundamental transport process that amplifies intracellular bilirubin redox actions, which can exacerbate insulin resistance and steatosis in obesity.

Lower Vestibular Incision: A Modified Technique of Dissection.

INTRODUCTION: Exposure to anterior mandible via conventional approach by either cervicular or vestibular incision is normally carried out for trauma or orthognathic surgery. Transection of mentalis muscle and reposition of the muscle is a key step. This prevents post-operative lip ptosis. MATERIAL AND METHODS: A modified dissection technique is presented in the article to identify the bilateral mentalis muscles at its insertion and isolate it in order to preserve it if feasible for access or to transect it after demarcating so that it can be reoriented in its native position. CONCLUSION: The modified method is an anatomically direct functional approach to the anterior mandible.

"Orofacial Dystonia-A Silent Killer": Mandibular Fractures with Orofacial Dystonia, A Report of a Case and Review.

Mandibular parasymphysis fracture is very commonly observed especially in old age when there is resorptions of the alveolar ridges. In cervical dystonia, there is centrally mediated disease in which there is uncontrolled and spasmodic contraction of the facial and the masticatory muscles. Due to the application of this sudden and uncontrolled force, there is a tendency of the bone to unfavourably remodel and weaken. The case presented here is of a geriatric patient who presented to us with a fracture at the right parasymphysis and left dentoalveolar region of the mandible and was suffering from cervical dystonia. Management of this case posed a challenge in every step, and it needed a resurgery where the fracture was managed by the placement of reconstruction plate. Not many cases in the literature have been reported where dystonic movements have resulted in the fracture of the mandible.

The structural basis of lipid scrambling and inactivation in the endoplasmic reticulum scramblase TMEM16K.

Membranes in cells have defined distributions of lipids in each leaflet, controlled by lipid scramblases and flip/floppases. However, for some intracellular membranes such as the endoplasmic reticulum (ER) the scramblases have not been identified. Members of the TMEM16 family have either lipid scramblase or chloride channel activity. Although TMEM16K is widely distributed and associated with the neurological disorder autosomal recessive spinocerebellar ataxia type 10 (SCAR10), its location in cells, function and structure are largely uncharacterised. Here we show that TMEM16K is an ER-resident lipid scramblase with a requirement for short chain lipids and calcium for robust activity. Crystal structures of TMEM16K show a scramblase fold, with an open lipid transporting groove. Additional cryo-EM structures reveal extensive conformational changes from the cytoplasmic to the ER side of the membrane, giving a state with a closed lipid permeation pathway. Molecular dynamics simulations showed that the open-groove conformation is necessary for scramblase activity.

Prevalence of rifampicin-resistant Mycobacterium tuberculosis among human-immunodeficiency-virus-seropositive patients and their treatment outcomes.

Multidrug resistant (MDR) and extensively drug resistant tuberculosis (TB) are a threat to the TB control programs in developing countries, and the situation is worsened by the human immunodeficiency virus (HIV) pandemic. This study was performed to correlate treatment outcome with the resistance patterns in HIV-seropositive patients coinfected with pulmonary TB. Sputum specimens were collected from 1643 HIV-seropositive patients and subjected to microscopy and liquid culture for TB. The smear- and culture-positive Mycobacterium tuberculosis isolates were subjected to Genotype MTBDRplus assay version 2.0. The M. tuberculosis culture-positivity rate was 39.44% (648/1643) among the 1643 HIV-seropositive patients and the overall MDR-TB rate was 5.6% (36/648). There were 421 newly diagnosed and 227 previously treated patients, among whom, MDR-TB was associated with 2.9% and 10.57% cases, respectively. The rate of rifampicin monoresistant TB among the cases of MDR-TB was 2.31% (15/648) and the rate of combined rifampicin and isoniazid resistance was 3.24% (21/648). The cure and death rates among the 20 registered cases were 30% (6/20) and 35% (7/20), respectively. Five cases were on treatment and two cases were defaulters among the 20 registered cases. High death rate (13, 36.1%, 95% confidence interval 20.8-53.8) was observed in this study among the patients who had mutations at the 530-533 codons. The present study emphasized the prerequisite to monitor the trend of drug-resistant TB in various mutant populations in order to timely implement appropriate interventions to curb the threat of MDR-TB.

Ocular morbidity patterns among children in schools for the blind in Chennai.

PURPOSE: To identify the morbidity patterns causing blindness in children attending schools for the blind in Chennai and comparing our data with similar studies done previously. METHODS: A cross-sectional prevalence study was carried out in two schools for the blind in Chennai. Blind schools were visited by a team of ophthalmologists and optometrists. Students with best-corrected visual acuity (BCVA) worse than 3/60 in the better eye were included and relevant history was noted. Every student underwent anterior segment evaluation and detailed fundus examination. Morbidity of the better eye was taken as cause of blindness. Health records maintained by the school were referred to wherever available. RESULTS: The anatomical causes of blindness include optic nerve disorders in 75 (24.8%) cases, retinal disorders in 55 (18.2%), corneal disorders in 47 (15.6%), lens-related disorders in 39 (12.9%), congenital anomalies in 11 (3.6%), and congenital glaucoma in 20 (6.6%) cases. The whole globe was involved in six cases (1.99%). Among conditions causing blindness, optic atrophy seen in 73 (24.17%) cases was the most common, followed by retinal dystrophy in 44 (14.56%), corneal scarring in 35 (11.59%), cataract in 22 (7.28%), and congenital glaucoma in 20 (6.6%) cases. CONCLUSION: It was found that avoidable causes of blindness were seen in 31% of cases and incurable causes in 45%. Optic nerve atrophy and retinal dystrophy are the emerging causes of blindness, underlining the need for genetic counseling and low vision rehabilitation centers, along with a targeted approach for avoidable causes of blindness.

Structure of the polycystic kidney disease TRP channel Polycystin-2 (PC2).

Mutations in either polycystin-1 (PC1 or PKD1) or polycystin-2 (PC2, PKD2 or TRPP1) cause autosomal-dominant polycystic kidney disease (ADPKD) through unknown mechanisms. Here we present the structure of human PC2 in a closed conformation, solved by electron cryomicroscopy at 4.2-Å resolution. The structure reveals a novel polycystin-specific 'tetragonal opening for polycystins' (TOP) domain tightly bound to the top of a classic transient receptor potential (TRP) channel structure. The TOP domain is formed from two extensions to the voltage-sensor-like domain (VSLD); it covers the channel's endoplasmic reticulum lumen or extracellular surface and encloses an upper vestibule, above the pore filter, without blocking the ion-conduction pathway. The TOP-domain fold is conserved among the polycystins, including the homologous channel-like region of PC1, and is the site of a cluster of ADPKD-associated missense variants. Extensive contacts among the TOP-domain subunits, the pore and the VSLD provide ample scope for regulation through physical and chemical stimuli.

Structures and functions of mitochondrial ABC transporters.

A small number of physiologically important ATP-binding cassette (ABC) transporters are found in mitochondria. Most are half transporters of the B group forming homodimers and their topology suggests they function as exporters. The results of mutant studies point towards involvement in iron cofactor biosynthesis. In particular, ABC subfamily B member 7 (ABCB7) and its homologues in yeast and plants are required for iron-sulfur (Fe-S) cluster biosynthesis outside of the mitochondria, whereas ABCB10 is involved in haem biosynthesis. They also play a role in preventing oxidative stress. Mutations in ABCB6 and ABCB7 have been linked to human disease. Recent crystal structures of yeast Atm1 and human ABCB10 have been key to identifying substrate-binding sites and transport mechanisms. Combined with in vitro and in vivo studies, progress is being made to find the physiological substrates of the different mitochondrial ABC transporters.

The Cryo-EM structure of the CorA channel from Methanocaldococcus jannaschii in low magnesium conditions.

CorA channels are responsible for the uptake of essential magnesium ions by bacteria. X-ray crystal structures have been resolved for two full-length CorA channels, each in a non-conducting state with magnesium ions bound to the protein: These structures reveal a homo-pentameric quaternary structure with approximate 5-fold rotational symmetry about a central pore axis. We report the structure of the detergent solubilized Methanocaldococcus jannaschii CorA channel determined by Cryo-Electron Microscopy and Single Particle Averaging, supported by Small Angle X-ray Scattering and X-ray crystallography. This structure also shows a pentameric channel but with a highly asymmetric domain structure. The asymmetry of the domains includes differential separations between the trans-membrane segments, which reflects mechanical coupling of the cytoplasmic domain to the trans-membrane domain. This structure therefore reveals an important aspect of the gating mechanism of CorA channels by providing an indication of how the absence of magnesium ions leads to major structural changes.

Purification and interaction analyses of two human lysosomal vitamin B12 transporters: LMBD1 and ABCD4.

Mutations in human LMBRD1 and ABCD4 prevent lysosomal export of vitamin B(12) to the cytoplasm, impairing the vitamin B(12)-dependent enzymes methionine synthase and methylmalonyl-CoA mutase. The gene products of LMBRD1 and ABCD4 are implicated in vitamin B(12) transport at the lysosomal membrane and are proposed to act in complex. To address the mechanism for lysosomal vitamin B(12) transport, we report the novel recombinant production of LMBD1 and ABCD4 for detailed biophysical analyses. Using blue native PAGE, chemical crosslinking, and size exclusion chromatography coupled to multi-angle light scattering (SEC-MALS), we show that both detergent-solubilized LMBD1 and detergent-solubilized ABCD4 form homodimers. To examine the functional binding properties of these proteins, label-free surface plasmon resonance (SPR) provides direct in vitro evidence that: (i) LMBD1 and ABCD4 interact with low nanomolar affinity; and (ii) the cytoplasmic vitamin B(12)-processing protein MMACHC also interacts with LMBD1 and ABCD4 with low nanomolar affinity. Accordingly, we propose a model whereby membrane-bound LMBD1 and ABCD4 facilitate the vectorial delivery of lysosomal vitamin B(12) to cytoplasmic MMACHC, thus preventing cofactor dilution to the cytoplasmic milieu and protecting against inactivating side reactions.

Structures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states.

ABCB10 is one of the three ATP-binding cassette (ABC) transporters found in the inner membrane of mitochondria. In mammals ABCB10 is essential for erythropoiesis, and for protection of mitochondria against oxidative stress. ABCB10 is therefore a potential therapeutic target for diseases in which increased mitochondrial reactive oxygen species production and oxidative stress play a major role. The crystal structure of apo-ABCB10 shows a classic exporter fold ABC transporter structure, in an open-inwards conformation, ready to bind the substrate or nucleotide from the inner mitochondrial matrix or membrane. Unexpectedly, however, ABCB10 adopts an open-inwards conformation when complexed with nonhydrolysable ATP analogs, in contrast to other transporter structures which adopt an open-outwards conformation in complex with ATP. The three complexes of ABCB10/ATP analogs reported here showed varying degrees of opening of the transport substrate binding site, indicating that in this conformation there is some flexibility between the two halves of the protein. These structures suggest that the observed plasticity, together with a portal between two helices in the transmembrane region of ABCB10, assist transport substrate entry into the substrate binding cavity. These structures indicate that ABC transporters may exist in an open-inwards conformation when nucleotide is bound. We discuss ways in which this observation can be aligned with the current views on mechanisms of ABC transporters.

US and CT evaluation of acute pelvic pain of gynecologic origin in nonpregnant premenopausal patients.

The interpretation of imaging findings in the premenopausal patient with acute pelvic pain is influenced by knowledge of the physiologic changes that occur in the pelvis as well as by the patient's clinical history. Although ultrasonography (US) is the modality of choice for initial imaging, gynecologic disease is detected or suspected with increasing frequency at computed tomography (CT) because of the increasing availability and use of this modality. As a result, the recognition of common features of gynecologic entities on both US and CT images is essential for prompt diagnosis and expeditious management. Categorizing lesions according to their anatomic location, physiologic or pathologic origin, and internal characteristics (cystic, solid, or mixed) allows efficient and accurate diagnosis.

Structural insights into P-glycoprotein (ABCB1) by small angle X-ray scattering and electron crystallography.

P-glycoprotein (ABCB1) is an ATP-binding cassette protein that is associated with the acquisition of multi-drug resistance in cancer and the failure of chemotherapy in humans. Structural insights into this protein are described using a combination of small angle X-ray scattering data and cryo-electron crystallography data. We have compared the structures with bacterial homologues, and discuss the development of homology models for P-glycoprotein based on the bacterial Sav1866 structure.