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The present report describes the management of tumorous growth in the ear canal of a dog with total ear canal ablation and lateral bulla osteotomy. Clinical examination revealed a severely stenotic ear canal along with palpable tumorous growth. The animal was premedicated with atropine, diazepam, and butorphanol. General anesthesia was induced with propofol and maintained using isoflurane with oxygen. Total ear canal ablation and lateral bulla osteotomy were performed according to the standard procedure. The closure of the surgical site was done in two layers using polyglactin 910. The skin was sutured by using polypropylene. Sutures were removed after 14 days. Post-operative antibiotics, analgesics, and nerve supplements were given. Complete recovery of the animal was seen without any post-surgical complications.

Medication adherence is crucial for managing respiratory conditions effectively. This study aimed to explore the multifaceted factors influencing medication adherence among patients with respiratory illnesses. A comprehensive analysis was conducted, focusing on patient demographics, characteristics, clinical factors, beliefs about medications, and reasons for irregular medication use. A cross-sectional design assessed medication adherence and beliefs in COPD patients through questionnaires. The study identified a middle-aged population (average age: 48.5 years) with high smoking prevalence, aligning with established COPD risk factors. Medication adherence scores indicated moderate levels (average ARMS score: 62.7), but with significant individual variation. Financial burden emerged as the primary barrier, with nearly 28% of participants reporting cost-related non-adherence, particularly impacting lower socioeconomic status (SES) patients. Social stigma regarding respiratory illness, a novel factor, influenced adherence, especially in urban areas (19.8% reported experiencing stigma). The study found a positive correlation between positive medication beliefs and adherence, highlighting the importance of fostering trust in treatment effectiveness. Additionally, a confirmed COPD diagnosis and specific inhaler devices (DPI, PMDI with spacer) were linked to improved adherence. This study identified significant factors impacting medication adherence in COPD, including financial constraints, social stigma, medication beliefs, and inhaler device type.

The “carpal boss” is a variant present in 19% of the population according to cadaveric studies but becomes symptomatic in only 1% of cases. With the rising popularity of “yoga,” which includes prolonged hyperextension at the wrist joint with weight bearing, an increasing number of individuals with silent carpal boss present with dorsal wrist pain due to impingement over the dorsal soft tissues by this innocuous bony protuberance. This warrants the attention of radiologists and clinicians while dealing with wrist pain. It can be challenging to identify this bossing on routine radiographs, necessitating special views. We describe the use of dynamic ultrasound in diagnosing “symptomatic” carpal boss, the effects of which become even more evident on imaging during hyperextension—the triggering movement.

Advertisement calls in frogs have evolved to be species-specific signals of recognition and are therefore considered an essential component of integrative taxonomic approaches to identify species and delineate their distribution range. The species rich genus Microhyla is a particularly challenging group for species identification, discovery and conservation management due to the small size, conserved morphology and wide distribution of its members, necessitating the need for a thorough description of their vocalization. In this study, we provide quantitative description of the vocal behaviour of Microhyla nilphamariensis, a widely distributed south Asian species, from Delhi, India, based on call recordings of 18 individuals and assessment of 21 call properties. Based on the properties measured acrossed 360 calls, we find that a typical advertisement call of M. nilphamariensis lasts for 393.5 ± 57.5 ms, has 17 pulses on average and produce pulses at rate of 39 pulses/s. The overall call dominant frequency was found to be 2.8 KHz and the call spectrum consisted of two dominant frequency peaks centered at 1.6 KHz and 3.6 KHz, ranging between 1.5–4.1 KHz. Apart from its typical advertisement call, our study also reveals the presence of three ‘rare’ call types, previously unreported in this species. We describe variability in call properties and discuss their relation to body size and temperature. We found that overall dominant frequency 1 (spectral property) was found to be correlated with body size, while first pulse period (temporal property) was found to be correlated with temperature. Further, we compare the vocal repertoire of M. nilphamariensis with that of the congener Microhyla ornata from the western coast of India and Sri Lanka and also compare the call properties of these two populations of M. ornata to investigate intra-specific call variation. We find statistically significant differentiation in their acoustic repertoire in both cases. Based on 18 call properties (out of 20), individuals of each locality clearly segregate on PCA factor plane forming separate groups. Discriminant function analysis (DFA) using PCA factors shows 100% classification success with individuals of each locality getting classified to a discrete group. This confirms significant acoustic differentiation between these species as well as between geographically distant conspecifics. The data generated in this study will be useful for comparative bioacoustic analysis of Microhyla species and can be utilized to monitor populations and devise conservation management plan for threatened species in this group.

Millet products have garnered global recognition for their exceptional nutritional profile, appealing to various age demographics, and, therefore, fortifying such products with minerals can ensure nutritional security. This research explores the feasibility of utilizing millet as a substitute for refined wheat flour in biscuit production. Three distinct millet varieties were investigated: finger, pearl, and buckwheat. Employing response surface methodology (RSM), the optimal ratio of these flours was determined, resulting in a blend of 1.5:1:1, respectively. The optimized multi-millet biscuits were further enhanced with calcium fortification and subjected to comprehensive physico-chemical analysis. Proximate composition analysis revealed favorable levels of protein (5.472 ± 0.31%), ash (2.80 ± 0.57 g/100 g), and energy density (5.8015 ± 0.004 kcal/g), indicating a significantly higher protein content, enriched mineral profile, and high energy density as compared to refined wheat flour products. Sensory evaluation encompassing attributes such as color and texture and organoleptic assessment using a nine-point hedonic scale demonstrated favorable acceptance. Additionally, the overall acceptability of the biscuits remained consistently high throughout storage, ranging from 8.263 ± 0.65 (day 0) to 8.053 ± 0.85 (day 14). This study underscores the potential of multi-millet biscuits as a nutritious and palatable alternative to traditional wheat-based snacks, offering an avenue for diversifying dietary options and promoting healthier food choices.

Wnt signaling involves multiple pathways that contribute to organ development, cell fate, inflammation, and normal stem cell renewal and maintenance. Although the homeostasis of stem cells in the gastrointestinal (GI) tract highly depends on the Wnt signaling pathway, this regulation is impaired in cancers and in aging. Overactive (uncontrolled) Wnt signaling can induce GI epithelial cancers such as colon and gastric cancer. Overactive Wnt signaling can also contribute to the initiation and progression of gastrointestinal stromal tumor, which is the most common human sarcoma occurring in the walls of the digestive organs, mainly the stomach and small intestine. Wnt expression is positively associated not only with the progression of oncogenesis but also with resistance to chemotherapy and radiotherapy. Of note, recent reports show that decreased Wnt signaling is related to intestinal stem cell aging and that overactivated Wnt signaling leads to gastric pacemaker stem cell aging in tunica muscularis. These findings indicate that Wnt signaling has different crucial aspects of cell fate determination with age in GI tunica mucosa and muscularis. In this review, we summarize the most recent advances in our understanding of Wnt signaling pathways and their role in regulating key aspects during development, carcinogenesis, inflammation, and aging, with the ultimate goal of identifying novel therapies.

Mesenchymal stem cells (MSCs) derived from bone marrow can support skeletal tissue repair and regeneration owing to their self-renewing capacity, differentiation ability, and trophic functions. Bone marrow-derived MSCs undergo dramatic changes with aging, including the senescence-associated secretory phenotype (SASP) which may largely contribute to age-related changes in bone tissue leading to osteoporosis. A mass spectrometry-based proteomics approach was used to investigate the MSC SASP. Replicative senescence was achieved by exhaustive in vitro sub-cultivation and confirmed by standard proliferation criteria. Conditioned media from non-senescent and senescent MSCs underwent mass spectrometry. Proteomics and bioinformatics analyses enabled the identification of 95 proteins expressed uniquely in senescent MSCs. Protein ontology analysis revealed the enrichment of proteins linked to the extracellular matrix, exosomes, cell adhesion, and calcium ion binding. The proteomic analysis was independently validated by taking ten identified proteins with relevance to bone aging and confirming their increased abundance in conditioned media from replicatively senescent versus non-senescent MSCs (ACTα2, LTF, SOD1, IL-6, LTBP2, PXDN, SERPINE 1, COL1α1, THBS1, OPG). These target proteins were used to further investigate changes in the MSC SASP profile in response to other inducers of senescence, ionizing radiation (IR) and H2O2. Similar secreted protein expression profiles with replicatively senescent cells were seen with H2O2 treatment except for LTF and PXDN, which were increased by IR treatment. With both IR and H2O2 treatment there was a decrease in THBS1. In vivo investigation of these secreted proteins with aging was shown by significant changes in the abundance of OPG, COL1α1, IL-6, ACTα2, SERPINE 1, and THBS1 in the plasma of aged rats. This unbiased, comprehensive analysis of the changes in the MSC secretome with senescence defines the unique protein signature of the SASP in these cells and provides a better understanding of the aging bone microenvironment.

Acute wrist injuries with ongoing ulnar-sided wrist pain warrant a magnetic resonance imaging (MRI) to diagnose ligamentous injuries. Triangular fibrocartilage complex (TFCC) tears have been classified and described in the literature but complex tear patterns have limited representation. Bucket-handle tears of the TFCC represent only 0.5% of TFCC tears and have recently been identified, posing a diagnostic and management challenge. Preoperative diagnosis is possible with MRI and necessary for optimal and early surgical management. The authors describe a unique case of a flipped tear of the central disc of the TFCC, where the fragment was flipped into the distal radioulnar joint, a site hidden during routine arthroscopy.

Due to modern medical advancements, greater proportions of the population will continue to age with longer life spans. Increased life span, however, does not always correlate with improved health span, and may result in an increase in aging-related diseases and disorders. These diseases are often attributed to cellular senescence, in which cells become disengaged from the cell cycle and inert to cell death. These cells are characterized by a proinflammatory secretome. The proinflammatory senescence-associated secretory phenotype, although part of a natural function intended to prevent further DNA damage, creates a microenvironment suited to tumor progression. This microenvironment is most evident in the gastrointestinal tract (GI), where a combination of bacterial infections, senescent cells, and inflammatory proteins can lead to oncogenesis. Thus, it is important to find potential senescence biomarkers as targets of novel therapies for GI diseases and disorders including cancers. However, finding therapeutic targets in the GI microenvironment to reduce the risk of GI tumor onset may also be of value. This review summarizes the effects of cellular senescence on GI aging, inflammation, and cancers, and aims to improve our understanding of these processes with a goal of enhancing future therapy.

Pyometra is one of the most common uterine pathologies of intact bitch at middle to advanced age. In the early stages, the disease shows subtle changes, making diagnosis a challenge. In contrast, at later stages, it manifests as potentially life-threatening systemic inflammatory response syndrome. Ultrasonographic examination of the uterus aids in the diagnosis, although it has limitation in ascertaining the clinical severity of pyometra. Moreover, differentiation of cystic endometrial hyperplasia from pyometra could not be discerned with greater accuracy. Therefore, false negative diagnosis of pyometra patients leads to development of systemic inflammatory response, which delays administration of therapies and results in deaths during early course of treatment. Further, indiscriminate use of broad-spectrum antimicrobials at higher dose in false positive cases considerably contributes to the rising pool of drug resistant pathogens, thereby increasing the risk of case fatality due to sepsis in a long-term. Monitoring the circulating pro-inflammatory cytokines, acute phase proteins, endotoxin, growth factors and inflammatory mediators is the current trend in pyometra research, especially for developing diagnostic and prognostic biomarkers. The present review deals with the prospects of developing diagnostic and prognostic biomarkers in the canine pyometra.

Abstract Purpose Peripheral neuropathies are a group of disorders which affect the peripheral nervous system which have been conventionally diagnosed using electrodiagnostic studies. This study was carried out to assess the role of imaging in diagnosing peripheral mononeuropathy as exact anatomical localisation of the pathology is possible using high-resolution ultrasound and MR neurography, the modalities assessed in this study. Method A hospital-based prospective analytical study was carried out in a resource-limited setting on 180 peripheral nerves in 131 patients with symptoms of peripheral mononeuropathy after taking IRB approval. Each patient underwent high-resolution ultrasound examination and MR neurography, findings of which were then compared and statistically analysed assuming electrodiagnostic findings as the gold standard. Results Overall, the diagnostic accuracy was highest for the proton density fat-saturated MR sequence (93.89%) followed by high-resolution ultrasound (80%). The sensitivity was highest for proton density fat-saturated sequence while the T1 MR sequence had the highest specificity. Combined diagnostic accuracy of both modalities was calculated to be 93.33% with a negative predictive value of 80%. High-resolution ultrasound and MRI equally detected the cases with nerve discontinuity, while neuromas were better identified on MRI. Conclusion With the advent of higher frequency probes and improved MR field strength, imaging of peripheral nerves is possible with better accuracy. Imaging assessment of nerves allows anatomical delineation with identification of exact site of involvement. This comparative study demonstrates the role of imaging in diagnosing peripheral nerve pathologies with the accuracy of MRI as high as 93.89% which may serve as an imaging gold standard. High-resolution ultrasound, being quicker, cost effective and a comparable accuracy of 80% can serve as a reliable screening tool. This study incorporates a larger study group and compares HRUS with MRI, taking NCV as gold standard, which has not been done in the preceding studies. With this study, we conclude that these two imaging modalities are not mutually exclusive. Rather, they complement each other and can be used in conjunction as an imaging yardstick for diagnosing peripheral neuropathies.

Aim: The present study was aimed to determine the normal reference values of M-mode echocardiographic measurements in healthy Indian Spitz dogs and evaluate the influence of gender and body weight on these measurements. Materials and Methods: M-mode echocardiography was performed in twenty-four clinically healthy conscious Indian Spitz dogs, aged 3-5 years and weighing 7-18 kg. Measurements were made from the right parasternal long axis left ventricular outflow tract view of the heart. The parameters recorded were: Left ventricular internal dimension, interventricular septal thickness and left ventricular posterior wall thickness during diastole and systole, left atrial diameter, aortic root diameter, left ventricular systolic functional parameters, and indices and mitral valve parameters. Results: M-mode echocardiographic measurements in healthy Indian Spitz dogs were standardized. Gender had no influence on echocardiographic measurements except mitral valve excursion amplitude and time interval between onset and end of mitral valve closure, which were significantly (p

Abstract The ulnar nerve is a branch of the C8 and T1 nerve roots and arises from the medial cord of the brachial plexus. It supplies the intrinsic muscles of the hand and assists the median nerve in functioning of the flexors. Also known as the musician’s nerve, it is the second most common nerve involved in compressive neuropathy following the median nerve. Common sites of entrapment include cubital tunnel at the elbow, the ulnar groove in the humerus and the Guyon’s canal at the wrist. Patients present with altered sensation in the ulnar fourth and the fifth digit and the medial side of arm with loss of function of intrinsic muscles of the hand, the flexor carpi ulnaris and ulnar fibres of flexor digitorum superficialis in more severe cases. Diagnosis relies on clinical examination, electrodiagnostic studies and imaging findings. Plain radiographs are used to identify fracture sites, callus, or tumours as cause of compression. Technological advances in ultrasonography have allowed direct visualisation of the involved nerve with assessment of exact site, extent and type of injury. It yields unmatched information about anatomical details of the nerve. MR imaging adds to soft tissue details and helps in characterising the lesion. This pictorial review aims to illustrate a wide spectrum of causes of ulnar neuropathies as seen on ultrasound and MRI and emphasises upon the importance of imaging modalities in the diagnosis of neuropathies.

ABSTRACT Changes in aging bone that lead to osteoporosis are mediated at multiple levels, including hormonal alterations, skeletal unloading, and accumulation of senescent cells. This pathological interplay is superimposed upon medical conditions, potentially bone‐wasting medications, modifiable and unmodifiable personal risk factors, and genetic predisposition that accelerate bone loss with aging. In this study, the focus is on bone hemostasis and its dysregulation with aging. The major physiological changes with aging in bone and the role of cellular senescence in contributing to age‐related osteoporosis are summarized. The aspects of bone aging are reviewed including remodeling deficits, uncoupling phenomena, inducers of cellular senescence related to bone aging, roles of the senescence‐associated secretory phenotype, radiation‐induced bone loss as a model for bone aging, and the accumulation of senescent cells in the bone microenvironment as a predominant mechanism for age‐related osteoporosis. The study also addresses the rationale and potential for therapeutic interventions based on the clearance of senescent cells or suppression of the senescence‐associated secretory phenotype. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Stem cell therapy has been extensively evaluated for its potential in managing neuronal diseases and disorders. The present study was performed to evaluate the therapeutic potential of allogenic bone marrow-derived mesenchymal stem cells (aBM-MSC) for the management of neural defects associated with vertebral compression fracture (VCF) in canine. Six clinical cases presented with the history of neural defects secondary to non-deviating VCFs were included in the present study. All the animals were subjected to detailed clinical, radiological, and haematological investigations and observations were recorded. The neurological defects in each case were graded based on routine neurological examination. The aBM-MSCs were isolated, cultured, and characterized as per ISCT criteria from the bone marrow collected from healthy dogs presented for elective surgery. The prepared cell suspension containing aBM-MSC at 3rd passage was utilized for transplantation in the clinical cases of VCF. Following the intraspinal administration of aBM-MSC, the dogs were treated with methylcobalamin and gabapentin orally throughout the study period. Improvement was evaluated on the basis of a detailed neurological examination. Significant improvement in locomotor status and sensory functions was observed in all the cases. Findings of the present study suggest that intraspinal administration of aBM-MSCs along with supportive therapy can be recommended as a therapeutic strategy for managing neural defects associated with non-deviating VCFs in canine patients.

Ever since it was first reported in Wuhan, China, the coronavirus-induced disease of 2019 (COVID-19) has become an enigma of sorts with ever expanding reports of direct and indirect effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on almost all the vital organ systems. Along with inciting acute pulmonary complications, the virus attacks the cardiac, renal, hepatic, and gastrointestinal systems as well as the central nervous system (CNS). The person-to-person variability in susceptibility of individuals to disease severity still remains a puzzle, although the comorbidities and the age/gender of a person are believed to play a key role. SARS-CoV-2 needs angiotensin-converting enzyme 2 (ACE2) receptor for its infectivity, and the association between SARS-CoV-2 and ACE2 leads to a decline in ACE2 activity and its neuroprotective effects. Acute respiratory distress may also induce hypoxia, leading to increased oxidative stress and neurodegeneration. Infection of the neurons along with peripheral leukocytes’ activation results in proinflammatory cytokine release, rendering the brain more susceptible to neurodegenerative changes. Due to the advancement in molecular biology techniques and vaccine development programs, the world now has hope to relatively quickly study and combat the deadly virus. On the other side, however, the virus seems to be still evolving with new variants being discovered periodically. In keeping up with the pace of this virus, there has been an avalanche of studies. This review provides an update on the recent progress in adjudicating the CNS-related mechanisms of SARS-CoV-2 infection and its potential to incite or accelerate neurodegeneration in surviving patients. Current as well as emerging therapeutic opportunities and biomarker development are highlighted.

Abstract The radial nerve has a long and tortuous course in the upper limb. Injury to the nerve can occur due to a multitude of causes at many potential sites along its course. The most common site of involvement is in the proximal forearm affecting the posterior interosseous branch while the main branch of the radial nerve is injured in fractures of the humeral shaft. Signs and symptoms of radial neuropathy depend upon the site of injury. Injury to the nerve distal to innervation of triceps brachii results in loss of extensor function with sparing of function of the triceps resulting in the characteristic ‘wrist drop’. Injury in the mid-arm is associated with loss of sensation in the dorsolateral aspect of the hand, the dorsal aspect of the radial three-and-a-half digits and in the first web space. Involvement of only the posterior interosseous nerve (PIN) results in weakness of the wrist and digit extensors. Diagnosis relies on clinical examination, electrodiagnostic studies and imaging findings. Plain radiographs are used to identify fracture sites, callus or tumours as cause of compression. Technological advances in ultrasonography have allowed direct visualisation of the involved nerve with assessment of the exact site, extent and type of injury. It yields unmatched information about anatomical details of the nerve. MR imaging adds to soft-tissue details and helps in characterising the lesion. This pictorial review aims to illustrate a wide spectrum of causes of radial neuropathy and emphasises the importance of imaging modalities in diagnosis of neuropathies. Teaching Points • Radial nerve injuries are assessed by clinical examination and diagnosed using electrodiagnostic and imaging studies. • Knowledge of anatomical relations and course of the nerve is necessary to identify the nerve at pre-determined anatomical locations. • Altered echogenicity and signal intensity, discontinuity of the nerve, focal thickening and cause of compression can be assessed by imaging modalities. • MR imaging helps in confirmation of the ultrasound findings, differentiating similar appearing lesions and provides additional soft-tissue details.

Mitochondria associated membranes (MAMs), as the name suggests, are the membranes that physically and biochemically connect mitochondria with endoplasmic reticulum. MAMs not only structurally but also functionally connect these two important organelles within the cell which were previously thought to exist independently. There are multiple points of communication between ER–mitochondria and MAMs play an important role in both ER and mitochondria functions such as Ca2+ homeostasis, proteostasis, mitochondrial bioenergetics, movement, and mitophagy. The number of disease-related proteins and genes being associated with MAMs has been continually on the rise since its discovery. There is an overwhelming overlap between the biochemical functions of MAMs and processes affected in neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). Thus, MAMs have received well-deserving and much delayed attention as modulators for ER–mitochondria communication and function. This review briefly discusses the recent progress made in this now fast developing field full of promise for very exciting future therapeutic discoveries.

Bone is a dynamic organ maintained by tightly regulated mechanisms. With old age, bone homeostasis, which is maintained by an intricate balance between bone formation and bone resorption, undergoes deregulation. Oxidative stress-induced DNA damage, cellular apoptosis, and cellular senescence are all responsible for this tissue dysfunction and the imbalance in the bone homeostasis. These cellular mechanisms have become a target for therapeutics to treat age-related osteoporosis. Genetic mouse models have shown the importance of senescent cell clearance in alleviating age-related osteoporosis. Furthermore, we and others have shown that targeting cellular senescence pharmacologically was an effective tool to alleviate age- and radiation-induced osteoporosis. Senescent cells also have an altered secretome known as the senescence associated secretory phenotype (SASP), which may have autocrine, paracrine, or endocrine function. The current review discusses the current and potential pathways which lead to a senescence profile in an aged skeleton and how bone homeostasis is affected during age-related osteoporosis. The review has also discussed existing therapeutics for the treatment of osteoporosis and rationalizes for novel therapeutic options based on cellular senescence and the SASP as an underlying pathogenesis of an aging bone.

Aim: To establish reference values of vertebral heart score (VHS) in Indian Spitz, Labrador retriever, and Mongrel dogs; to assess applicability of VHS in these three dog breeds; to determine if breed, recumbency side, gender, body weight, and thoracic depth (TD) to thoracic width (TW) ratio has an influence on the VHS measurement in these dog breeds. Materials and Methods: A total of 60, client owned, clinically healthy Indian Spitz (n=20, mean age = 4.25±2.15 years, body weight = 11.87±2.7 kg), Labrador retriever (n=20, mean age = 4.75±1.91 years, body weight = 27.31±5.43 kg), and Mongrel dogs (n=20, mean age = 4.25±1.52 years, body weight = 16.25±3.99 kg), having no radiological and clinical signs of cardiovascular or pulmonary disease were included in the study. All dogs were restrained manually and left lateral (LL) and right lateral (RL) radiographic views were obtained. The size of heart in lateral radiographs was calculated using VHS method. Besides, the TD, TW and TD: TW were calculated to determine the type of thoracic conformation in the dog breeds. In addition to this, the effect of breed, side of recumbency, gender, body weight, and TD to TW ratio on the calculation of VHS was determined. Results: VHS was calculated in all the animals of the breeds. VHS in Spitz and Labrador retriever was significantly (p9.7±0.5 v. RL and LL VHS in Mongrel dog was significantly (p9.7±0.5 v. Significant (p

We report a case report of Candida albicans suture infiltrate on 3rd post-op day in a 53 year female operated for penetrating keratoplasty. Candida albicans was identified by KOH mount, Gram Staining, germ tube, growth at 450C, chlamydospore formation and light green color on CHROMagar with sugar assimilation and culture characteristics. Despite being susceptible to Fluconazole by broth microdilution, patient did not respond to 0.3% fluconazole eye drops. On antifungal susceptibility testing by CLSI44A, it was susceptible to only Amphotericin B (100units). Patient was then started on 0.15% fortified amphotericin B eye drops resulting in complete resolution of infiltrates.

The original article [1] contained an omission in authorship detail; authors Aakanksha Agarwal and Abhishek Chandra are instead joint first authors.

Hyperhomocysteinemia induced by the C677T genetic variant in MTHFR (methylenetetrahydrofolate reductase) has been implicated in neuronal cell death of retinal ganglion cells (RGC), which is a characteristic feature of glaucoma. However, association of MTHFR C677T with glaucoma has been controversial because of inconsistent results across association studies. Association between MTHFR C677T and glaucoma has not been reported in Indian population. Therefore, with a focus on neurodegenerative death of RGC in glaucoma, the current study aimed to investigate association of MTHFR C677T with Primary Open Angle Glaucoma (POAG) and Primary Angle Closure Glaucoma (PACG) in a North Indian population. A total of 404 participants (231 patients and 173 controls) were included in this study. Genotyping was performed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism. A few random samples were also tested by direct sequencing. Genotypic and allelic distributions of the POAG and PACG cohorts were compared to that of controls by chi-square test and odds ratios were reported with 95% confidence intervals. Genotypic and allelic distributions between POAG cases and controls were significantly different (p = 0.03 and p = 0.01 respectively). Unlike POAG, we did not find significant difference in the genotypic and allelic distributions of C677T between PACG cases and controls (p>0.05). We also observed a higher proportion of TT associated POAG in females than that in males. However, this is a preliminary indication of gender specific risk of C677T that needs to be replicated in a larger cohort of males and females. The present investigation on MTHFR C677T and glaucoma reveals that the TT genotype and T allele of this polymorphism are significant risk factors for POAG but not for PACG in North Indian population. Ours is the first report demonstrating association of MTHFR C677T with POAG but not PACG in individuals from North India.

Intermittent administration of parathyroid hormone (PTH) dramatically increases bone mass and currently is one of the most effective treatments for osteoporosis. However, the detailed mechanisms are still largely unknown. Here we demonstrate that conditioned media from PTH-treated osteoblastic and osteocytic cells contain soluble chemotactic factors for bone marrow mesenchymal progenitors, which express a low amount of PTH receptor (PTH1R) and do not respond to PTH stimulation by increasing cAMP production or migrating toward PTH alone. Conditioned media from PTH-treated osteoblasts elevated phosphorylated Akt and p38MAPK amounts in mesenchymal progenitors and inhibition of these pathways blocked the migration of these progenitors toward conditioned media. Our previous and current studies revealed that PTH stimulates the expression of amphiregulin, an epidermal growth factor (EGF)-like ligand that signals through the EGF receptor (EGFR), in both osteoblasts and osteocytes. Interestingly, conditioned media from PTH-treated osteoblasts increased EGFR phosphorylation in mesenchymal progenitors. Using several different approaches, including inhibitor, neutralizing antibody, and siRNA, we demonstrate that PTH increases the release of amphiregulin from osteoblastic cells, which acts on the EGFRs expressed on mesenchymal progenitors to stimulate the Akt and p38MAPK pathways and subsequently promote their migration in vitro. Furthermore, inactivation of EGFR signaling specifically in osteoprogenitors/osteoblasts attenuated the anabolic actions of PTH on bone formation. Taken together, these results suggest a novel mechanism for the therapeutic effect of PTH on osteoporosis and an important role of EGFR signaling in mediating PTH's anabolic actions on bone.

The present report describes the management of tumorous growth in the ear canal of a dog with total ear canal ablation and lateral bulla osteotomy. Clinical examination revealed a severely stenotic ear canal along with palpable tumorous growth. The animal was premedicated with atropine, diazepam, and butorphanol. General anesthesia was induced with propofol and maintained using isoflurane with oxygen. Total ear canal ablation and lateral bulla osteotomy were performed according to the standard procedure. The closure of the surgical site was done in two layers using polyglactin 910. The skin was sutured by using polypropylene. Sutures were removed after 14 days. Post-operative antibiotics, analgesics, and nerve supplements were given. Complete recovery of the animal was seen without any post-surgical complications. [ABSTRACT FROM AUTHOR]