A Patient of Tumour Induced Osteomalacia Undiagnosed for 11 years.

We report a 45 years old woman, bedridden due to severe bone pain, back pain, multiple spontaneous fractures over 10 years. She had low serum Phosphates. We detected a swelling in her right groin and suspected tumour induced osteomalacia. Resection of the tumour led to reversal of metabolic bone disease. Patient became ambulatory within 6 weeks of tumour resection.

PPIP5K1 modulates ligand competition between diphosphoinositol polyphosphates and PtdIns(3,4,5)P3 for polyphosphoinositide-binding domains.

We describe new signalling consequences for PPIP5K1 (diphosphoinositol pentakisphosphate kinase type 1)-mediated phosphorylation of InsP6 and 5-InsP7 to 1-InsP7 and InsP8. In NIH 3T3 cells, either hyperosmotic stress or receptor activation by PDGF (platelet-derived growth factor) promoted translocation of PPIP5K1 from the cytoplasm to the plasma membrane. The PBD1 (polyphosphoinositide-binding domain) in PPIP5K1 recapitulated that translocation. Mutagenesis of PBD1 to reduce affinity for PtdIns(3,4,5)P3 prevented translocation. Using surface plasmon resonance, we found that PBD1 association with vesicular PtdIns(3,4,5)P3 was inhibited by InsP6 and diphosphoinositol polyphosphates. However, the inhibition by PPIP5K1 substrates (IC50: 5-InsP7=5 µM and InsP6=7 µM) was substantially more potent than that of the PPIP5K1 products (IC50: InsP8=32 µM and 1-InsP7=43 µM). This rank order of ligand competition with PtdIns(3,4,5)P3 was also exhibited by the PH (pleckstrin homology) domains of Akt (also known as protein kinase B), GRP1 (general receptor for phosphoinositides 1) and SIN1 (stress-activated protein kinase-interaction protein 1). We propose that, in vivo, PH domain binding of InsP6 and 5-InsP7 suppresses inappropriate signalling ('noise') from stochastic increases in PtdIns(3,4,5)P3. That restraint may be relieved by localized depletion of InsP6 and 5-InsP7 at the plasma membrane following PPIP5K1 recruitment. We tested this hypothesis in insulin-stimulated L6 myoblasts, using mTOR (mechanistic/mammalian target of rapamycin)-mediated phosphorylation of Akt on Ser473 as a readout for SIN1-mediated translocation of mTORC (mTOR complex) 2 to the plasma membrane [Zoncu, Efeyan and Sabatini (2011) Nat. Rev. Mol. Cell Biol. 12, 21-35]. Knockdown of PPIP5K1 expression was associated with a 40% reduction in Ser473 phosphorylation. A common feature of PtdIns(3,4,5)P3-based signalling cascades may be their regulation by PPIP5K1.

Membrane phosphoinositides and protein-membrane interactions.

Proteins with polybasic clusters bind to negatively charged phosphoinositides at the cell membrane. In this review, I have briefly discussed the types of phosphoinositides naturally found on membrane surfaces and how they recruit protein complexes for carrying out the process of signal transduction. A large number of researchers from around the world are now focusing their attention on protein-membrane binding, as these interactions have started to offer us a much better insight into the process of cell signaling. The main areas discussed in this brief review article include the phosphoinositide binding specificities of proteins and the role of their lipid binding in signaling processes downstream of membrane recruitment.

Defining signal transduction by inositol phosphates.

Ins(1,4,5)P(3) is a classical intracellular messenger: stimulus-dependent changes in its levels elicits biological effects through its release of intracellular Ca(2+) stores. The Ins(1,4,5)P(3) response is "switched off" by its metabolism to a range of additional inositol phosphates. These metabolites have themselves come to be collectively described as a signaling "family". The validity of that latter definition is critically examined in this review. That is, we assess the strength of the hypothesis that Ins(1,4,5)P(3) metabolites are themselves "classical" signals. Put another way, what is the evidence that the biological function of a particular inositol phosphate depends upon stimulus dependent changes in its levels? In this assessment, examples of an inositol phosphate acting as a cofactor (i.e. its function is not stimulus-dependent) do not satisfy our signaling criteria. We conclude that Ins(3,4,5,6)P(4) is, to date, the only Ins(1,4,5)P(3) metabolite that has been validated to act as a second messenger.

Management of recurrent intra corneal epithelial cyst with ethanol irrigation and vacuum-assisted cyst wall excision.

The clinical and pathological features and management of a patient with recurrent intracorneal epithelial cyst are reported. A child presented with a large intracorneal cyst and underwent drainage with 96 % ethanol irrigation. Histopathology confirmed the epithelial nature of the cyst. The cyst recurred, however, and subsequently a repeat ethanol irrigation with removal of the cyst wall was done. The cyst wall was vacuumed to ensure complete removal of epithelial cells. There was no recurrence, with good visual and cosmetic recovery. Intracorneal epithelial cysts can be successfully managed with drainage, 96 % ethanol irrigation, and vacuum-assisted cyst wall excision.

Agricultural Rotavator Induced Polytrauma in a 11-years-old Child - A Case Report.

Introduction: Agricultural polytrauma injuries in children are rare. Rotating blades of a rotavator can cause devastating injuries. Case Report: An 11-year-old male child presented with severe facial avulsion injuries, degloving injury of left lower limb, grade IIIB compound left tibia shaft fracture with a large butterfly fragment, and closed right tibia shaft fracture. General anesthesia through tracheostomy intubation was given. Simultaneous surgical intervention for the face and limbs was performed by a team of experts. The facial injury was debrided and repaired. After thorough debridement, compound left tibia fracture fixation was performed with two interfragmentary screws and neutralizing ankle-spanning external fixator. The closed right tibia shaft fracture was treated with closed elastic intramedullary nailing. Simultaneous debridement of degloving injuries over both thighs was performed and wound closure was done. Subsequently, the patient underwent debridement of wounds and vacuum-assisted closure 3 times with split skin grafting for the left leg. All fractures healed well at 6 months and the child was able to do all activities without any functional limitations. Conclusion: Agricultural injuries in Children can be devastating and should be managed using a multidisciplinary approach at a tertiary care center. A tracheostomy is a viable option for securing the airway in severe facial avulsion injuries. In a hemodynamically stable child, definitive fixation can be performed in a polytrauma situation and an external fixator can be used as a definitive implant in an open long bone fracture.

An isolated subcutaneous paraspinal pseudo-tumor-more to it than meets the eye-a case report and review of literature.

A 4-year-old male child presented to us with a paraspinal pseudo-tumor over the mid-back region with pain being his only symptom. On initial ultrasonography, it was presumed to be a nerve sheath tumor, but on an excision biopsy and histopathology, it proved to be a subcutaneous cysticercosis. Furthermore, an MRI of the brain showed a ring enhancing lesion with vasogenic edema, which confirmed the diagnosis of a neurologically symptomless neurocysticercosis. We treated the patient with albendazole and a short course of dexamethasone. There was complete resolution of the painful subcutaneous swelling, and the patient remained neurologically symptomless at all subsequent follow-ups. Resolution of the brain lesions was seen in the 6-month MRI follow-up. Although rare, orthopedic surgeons should consider the possibility of parasitic infections when dealing with small near-asymptomatic soft tissue paraspinal swellings of uncertain etiology. A thorough investigation in such cases can be lifesaving.

Autologous serum eye drops in dry eye disease: Preferred practice pattern guidelines.

Autologous serum eye drops provide lubrication and promote epithelial healing. They have been successfully used in the management of ocular surface disorders such as dry eye disease, persistent epithelial defects and neurotrophic keratopathy for many decades. A great deal of variation in the methods of preparation of autologous serum eye drops, the end concentration and the duration of use exists in published literature. In this review, simplified recommendations for preparation, transport, storage and use of autologous serum are described. Evidence for the use of this modality in aqueous deficient dry eye disease is summarized, along with expertise-based rationale.

Genome-wide structural analysis reveals novel membrane binding properties of AP180 N-terminal homology (ANTH) domains.

An increasing number of cytosolic proteins are shown to interact with membrane lipids during diverse cellular processes, but computational prediction of these proteins and their membrane binding behaviors remains challenging. Here, we introduce a new combinatorial computation protocol for systematic and robust functional prediction of membrane-binding proteins through high throughput homology modeling and in-depth calculation of biophysical properties. The approach was applied to the genomic scale identification of the AP180 N-terminal homology (ANTH) domain, one of the modular lipid binding domains, and prediction of their membrane binding properties. Our analysis yielded comprehensive coverage of the ANTH domain family and allowed classification and functional annotation of proteins based on the differences in local structural and biophysical features. Our analysis also identified a group of plant ANTH domains with unique structural features that may confer novel functionalities. Experimental characterization of a representative member of this subfamily confirmed its unique membrane binding mechanism and unprecedented membrane deforming activity. Collectively, these studies suggest that our new computational approach can be applied to genome-wide functional prediction of other lipid binding domains.

Receptor-dependent compartmentalization of PPIP5K1, a kinase with a cryptic polyphosphoinositide binding domain.

The inositol pyrophosphates are multifunctional signalling molecules. One of the families of enzymes that synthesize the inositol pyrophosphates are the Vip1/PPIP5Ks (PP-InsP5 kinases). The kinase domains in Vip1/PPIP5Ks have been mapped to their N-terminus. Each of these proteins also possess a phosphatase-like domain of unknown significance. In the present study, we show that this phosphatase-like domain is not catalytically active. Instead, by using SPR (surface plasmon resonance) to study protein binding to immobilized lipid vesicles, we show that this domain is specialized for binding PtdIns(3,4,5)P3 (PPIP5K1 K(d)=96 nM; PPIP5K2 K(d)=705 nM). Both PtdIns(3,4)P2 and PtdIns(4,5)P2 are significantly weaker ligands, and no significant binding of PtdIns(3,5)P2 was detected. We confirm the functional importance of this domain in inositol lipid binding by site-directed mutagenesis. We present evidence that the PtdIns(3,4,5)P3-binding domain is an unusual hybrid, in which a partial PH (pleckstrin homology) consensus sequence is spliced into the phosphatase-like domain. Agonist-dependent activation of the PtdIns 3-kinase pathway in NIH 3T3 cells drives translocation of PPIP5K1 from the cytosol to the plasma membrane. We have therefore demonstrated receptor-regulated compartmentalization of inositol pyrophosphate synthesis in mammalian cells.

Cochlear Implant Surgery During the Covid Pandemic Lockdown-The KEM Hospital, Pune Experience.

In response to the Covid 19 pandemic many governments and professional bodies recommended cancellation of elective surgeries including cochlear implantation. Resumption of elective surgeries was recommended after appropriate permissions were given by the authorities and the hospital had adequate infrastructure in terms of equipment and manpower to start elective surgeries without compromising on patient safety and care. We began cochlear implant surgeries in April 2020. We have done 5 cochlear implants surgeries till date. This manuscript discusses the changes that we did in our preoperative, intraoperative and postoperative protocol.

Inflammation and dry eye disease-where are we?

The presence of inflammation in dry eye disease (DED) results in increased patient symptomatology, ocular surface damage and worsening tear dysfunction. It also affects the health of meibomian glands and their secretions which further aggravates ocular surface disease. This article reviews current knowledge regarding ocular surface inflammation in DED and explores the relationships between the vicious cycles of DED, inflammation and meibomian gland dysfunction (MGD). The clinical evaluation of eyes with such changes, markers that identify the presence of inflammation on the ocular surface and current treatment options are discussed.

A Proposed Grading System and Experience of COVID-19 Associated Rhino Orbito Cerebral Mucormycosis from an Indian Tertiary Care Center.

Mucormycosis is an opportunistic fungal infection. India faced an unprecedented increase in patients with post coronavirus disease 2019 (COVID-19) associated rhino-orbito-cerebral mucormycosis (ROCM). This study proposes a grading system which correlates the extent of the disease with the management plan. An observational study was conducted January 2021-June 2021. We identified 65 patients. Eleven patients had mild disease, 27 patients had moderate, 16 patients were severe and 11 patients were graded as very severe. The management was planned based on this grading system. Early diagnosis, aggressive surgical debridement and antifungal drug therapy is the key to improve survival in ROCM. Procedures such as endoscopic orbital clearance, sublabial maxillectomy, and modified endoscopic Denkers (MED) approach facilitate access and surgical debridement. The new grading system proposed assists in planning the approach and extent of surgical debridement.

Selective Endothelialectomy in Peters Anomaly: A Novel Surgical Technique and Its Clinical Outcomes in Children.

PURPOSE: This study describes the surgical outcomes of selective endothelialectomy in Peters anomaly (SEPA), a relatively new technique to manage Peters anomaly (PA). METHODS: This study included 34 eyes of 28 children who had a visually significant posterior corneal defect due to PA and underwent SEPA between 2012 and 2019. A selective endothelialectomy from the posterior corneal defect was performed while preserving Descemet membrane. The primary outcome measure was the resolution of corneal opacification. The secondary outcome measures were functional vision, complications, and risk factors for failure. RESULTS: At a mean postoperative follow-up of 0.96 ± 0.20 years, 29 eyes (85.3%) maintained a successful outcome. Mean preoperative and postoperative best-corrected visual acuities were 2.55 ± 0.13 and 1.78 ± 0.13 ( P < 0.0001), respectively. Ambulatory functional visual improvement was seen in 97%, and 23% attained vision ranging between 20/190 and 20/50. Corneal opacification failed to clear in 5 eyes (15%). Risk factors associated with surgical failure were female sex ( P = 0.006), disease severity ( P < 0.0001), glaucoma ( P = 0.001), and additional interventions after SEPA ( P = 0.002). In multivariate analysis, only disease severity (ie, a type 2 PA) was a significant risk factor for the failure of SEPA. There were no sight-threatening complications. CONCLUSIONS: SEPA is a safe and effective technique in select cases of posterior corneal defect due to PA. SEPA could be a potential surgical alternative to pediatric keratoplasty or optical iridectomy in children with central corneal opacification smaller than 7 mm due to PA.

Mitomycin C therapy for corneal intraepithelial neoplasia masquerading as limbal stem cell deficiency with recurrent epithelial defect.

Diagnosis of corneal intraepithelial neoplasia was missed in a patient who presented with recurrent large epithelial defects with pannus. The patient was eventually diagnosed and successfully treated with topical mitomycin C. Mitomycin C may be preferable to surgery in lesions with extensive corneal involvement. Impression cytology should be used for early diagnosis in suspicious lesions.

Retrospective analysis of silicon intubation by Ritleng probe and Sutupak suture fixed in silicone tube in congenital nasolacrimal duct obstruction.

Purpose: The aim of this study was to perform a retrospective review of the outcome of silicon intubation using the Ritleng probe and a modified braided silk suture (Ethicon Sutupak) fixed in a silicone tube in children with congenital nasolacrimal duct obstruction (CNLDO). Methods: Records of all children between 1 and 12 years of age who underwent silicone tube intubation with the Ritleng probe and Ethicon Sutupak suture (2-0) fixed in silicone tube for CNLDO with a minimum of 1-year follow-up were identified. The hollow Ritleng probe was inserted via the canaliculus into the inferior meatus. The Sutupak thread-guide, attached to the silicone tube, was advanced through the probe lumen and retrieved using a hook under endoscopic visualization. The tube ends were tied to each other and tube removal was planned after 3 months. Absence of watering, discharge, and matted lashes after removal of silicone tube was defined as success. Results: One hundred and fifty-two eyes of 152 children with a mean age of 3.26 ± 2.3 years were included in the study. The procedure was successful in 145 eyes (95%) after removal of the silicone intubation with relief of symptoms observed in most patients by fifth-day follow-up (n = 120 eyes, 83%). The mean duration of follow-up was 3.48 ± 1.3 years. No other significant differences were observed between patients who did (n = 47) and did not (n = 105) have previous probing including success rates (95% vs. 96%, P = 0.89). Conclusion: Silicone intubation with Ritleng probe and Sutupak suture fixed in silicone tube was successful in resolution of symptoms of CNLDO in majority of patients. Using a low-cost suture did not affect success rates.

Does Patellar Resurfacing Matter? Midterm Follow-Up of MRK Total Knee Replacement.

BACKGROUND: Many designs of TKR have been developed to optimize the kinematics and improve satisfaction, including the 'medial rotating' philosophy. The purpose of this study is to report the mid-term clinical outcome of MRK knees and evaluate whether resurfacing the patella makes any difference in outcome. METHODS: A retrospective analysis was done of 104 MRK total knee replacement done between 2008 and 2017. Patients were called for a review for evaluation of OKS, Baldini and Feller scores. Demographics of the patients, clinical outcome, complications were assessed. RESULTS: 62 had patellar resurfacing. Mean follow-up was 74.45 months in non- resurfaced and 54.93 months in resurfaced group. Mean flexion range in both groups at final follow-up was 101.45. Median OKS at follow-up was 36 (12-47) in non-resurfaced and 37 (9-48) in resurfaced group. Patella scores were better in resurfaced group-Baldini score median (range) was 90 (25-100) in non-resurfaced v/s 100 (30-100) in resurfaced, Feller score median (range) was 25 (12-30) in non-resurfaced v/s 28 (10-30) (p 0.042) in resurfaced. The patellofemoral component of the OKS (Q5 + Q7 + Q12) median showed an improvement from 3 (1-11) to 6.5 (3-11) in non-resurfaced and from 3 (0-12) to 8 (2-12) (p 0.039) in resurfaced group. There were five complications overall (4.8%). CONCLUSION: These results show a satisfactory outcome at mid-term follow-up. We found a statistically significant difference in Feller score and in the patellofemoral component of OKS between the groups of MRK knee suggesting specific benefits of patellar resurfacing with this implant.

Bilateral non-resolving punctate keratitis in a keratoplasty patient.

This study aimed to report a case of non-resolving bilateral coarse punctate keratitis in a patient with prior bilateral penetrating keratoplasty. In view of non-response to antivirals, corneal epithelial scraping was carried out, which revealed the presence of microsporidial cysts. The infection resolved after a period of 12 days following the diagnosis, during which steroids were discontinued. Microsporidial keratitis needs to be considered in non-resolving coarse punctate keratitis and microbiologic evaluation is essential to establish the diagnosis.

Allergic conjunctivitis in children: current understanding and future perspectives.

PURPOSE OF REVIEW: The rising global burden of allergic diseases, particularly in the pediatric population, is of serious concern. Ocular allergy is one of the most common ocular pathologies met in clinical practice. A large proportion of children and adolescents suffer from allergic eye diseases (AEDs), which affect their quality of life. The available treatments and surgical modalities have their limitations and side effects. Therefore, the development of novel and alternate strategies is the need of the hour and requires a timely review of currently available knowledge. RECENT FINDINGS: The current review covers the incidence and prevalence of AEDs, factors influencing occurrence and severity of AED (age, sex, socioeconomic status etc.), underlying mechanisms, role of allergy testing and immunotherapy in children, development of diagnostic markers and novel therapies including cells and molecules. SUMMARY: Understanding the demographics, clinical patterns and risk factors of AED can help formulate appropriate preventive and therapeutic strategies for the effective management of this common cause of ocular morbidity. The future therapeutics for AED seems to rely primarily on cells (mesenchymal stem cells, Tregs, mast cells), cell products, molecules with immunosuppressive potential and immunotherapy.

A Narrative Review of Microsporidial Infections of the Cornea.

Microsporidia are a rare and commonly misdiagnosed cause of corneal infection, accounting for approximately 0.4% of cases of microbial keratitis in some populations. Ocular microsporidiosis most often presents as either microsporidial keratoconjunctivitis (MKC) or microsporidial stromal keratitis (MSK). Though these two clinical entities exhibit similar symptomology, they are distinguished from one another by the time course for disease progression, findings on slit-lamp examination, and response to medical therapy. This review summarizes the current literature on the etiology and clinical presentation of microsporidial infections of the cornea and highlights ongoing developments in available diagnostic modalities and treatment regimens.