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Bone fracture is a severe health concern; therefore, understanding the causes of bone fracture are crucial. This paper investigates the microstructure and fracture behaviour of cadaveric cortical bone of two different groups (Young, n= 6; Aged, n=7). The microstructure is obtained from µ-CT images, and the material parameters are measured with nanoindentation. Fracture behaviour in transverse and longitudinal orientations is investigated experimentally and numerically. The results show that the Haversian canal (HC) size increases and the osteon wall thickness (OWT) decreases significantly in the aged group, whereas a nonsignificant difference is found in tissue properties. The crack initiation (Jic) and crack growth (Jgrow) toughness of the aged group are found to be significantly lower (p

Context Increased bone fragility and reduced energy absorption to fracture associated with type 2 diabetes (T2D) cannot be explained by bone mineral density alone. This study, for the first time, reports on alterations in bone tissue’s material properties obtained from individuals with diabetes and known fragility fracture status. Objective To investigate the role of T2D in altering biomechanical, microstructural, and compositional properties of bone in individuals with fragility fracture. Methods Femoral head bone tissue specimens were collected from patients who underwent replacement surgery for fragility hip fracture. Trabecular bone quality parameters were compared in samples of 2 groups, nondiabetic (n = 40) and diabetic (n = 30), with a mean duration of disease 7.5 ± 2.8 years. Results No significant difference was observed in aBMD between the groups. Bone volume fraction (BV/TV) was lower in the diabetic group due to fewer and thinner trabeculae. The apparent-level toughness and postyield energy were lower in those with diabetes. Tissue-level (nanoindentation) modulus and hardness were lower in this group. Compositional differences in the diabetic group included lower mineral:matrix, wider mineral crystals, and bone collagen modifications—higher total fluorescent advanced glycation end-products (fAGEs), higher nonenzymatic cross-link ratio (NE-xLR), and altered secondary structure (amide bands). There was a strong inverse correlation between NE-xLR and postyield strain, fAGEs and postyield energy, and fAGEs and toughness. Conclusion The current study is novel in examining bone tissue in T2D following first hip fragility fracture. Our findings provide evidence of hyperglycemia’s detrimental effects on trabecular bone quality at multiple scales leading to lower energy absorption and toughness indicative of increased propensity to bone fragility.

To determine the diagnostic cut-offs and the prevalence of sarcopenia in India. Indians have lower muscle strength and muscle mass than Caucasians. The prevalence of ‘probable sarcopenia’, ‘sarcopenia’, and ‘severe sarcopenia’ is 14.6%, 3.2%, and 2.3%, respectively; corresponding values are higher using well-established Western cut-offs. Indigenous and not Western cut-offs should be used to define sarcopenia in Indians. Comprehensive data on diagnosis and prevalence of sarcopenia in India are lacking. The present study was undertaken to determine cut-offs for low muscle strength (MS) and low muscle mass (MM), and find out the prevalence of sarcopenia in Indians. Apparently healthy individuals aged ≥ 20 years with no prior history of any co-morbidities were recruited from community by door-to-door survey. Participants eligible for study underwent blood sampling. Individuals identified as having biochemical abnormalities that could potentially affect MS and MM were excluded. Enrolled participants underwent DEXA. Muscle mass, MS, and physical performance were expressed as appendicular skeletal muscle index (ASMI), dominant handgrip strength (HGS), and usual gait speed (GS), respectively. Cut-offs for low MS and MM were defined as HGS and ASMI 2SD

Objective: Hypophosphatemic rickets with hypercalciuria (HHRH) is a rare, recessively-inherited form of rickets caused by homozygous or compound heterozygous mutations in the SLC34A3 gene that encodes the renal tubular phosphate transporter protein NaPi2c. The bone phenotype varies from severe rickets to no disease. Accurate diagnosis is important as the treatment differs from other forms of rickets. Methods: The patient was a 12-year-old boy from the Indian subcontinent with florid hypophosphatemic rickets. A targeted gene panel to search for mutations in genes associated with inherited forms of rickets was performed. We also completed a literature search of published cases of HHRH. Results: The targeted gene panel demonstrated a novel homozygous SLC34A3 mutation: c.1339 G>A (p.Ala447Thr). His parents were heterozygous for the mutation. In our literature review we found that people with homozygous SLC34A3 mutations were more likely to have rickets than those with compound heterozygous mutations (85% versus 45%, p

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of hip and vertebral fractures. The increased fracture risk has largely been attributed to poor bone quality and microarchitecture. The contribution of bone quantity, measured as areal bone mineral density (BMD), to the risk of fracture is variable with most studies showing an increase in BMD in T2DM. The present study was undertaken to find out the prevalence of osteoporosis and osteopenia (based on BMD) in a cohort of patients with T2DM and delineate the possible modifiable and non-modifiable risk factors. In this cross-sectional observational study, 252 otherwise ostensibly healthy patients with T2DM underwent dual energy X-ray absorptiometry (DEXA) scan. Osteoporosis and osteopenia were defined based on T-scores. The effect of modifiable and non-modifiable risk factors on BMD and osteoporosis were assessed. The mean age of the cohort was 59.9 years with a M:F ratio 2.9:3.4. The mean BMD at the lumbar spine and hip were 0.892 g/cm2 and 0.715 g/cm2, respectively. Males had significantly higher BMD at both the sites compared to females. The prevalence of osteoporosis and osteopenia was 33% and 40%, respectively. Female gender, increasing age, normal body mass index (BMI), low serum 25-hydroxyvitamin D, and use of pioglitazone were significantly associated with the risk of osteoporosis. The prevalence of osteoporosis and osteopenia in patients with T2DM is high. Female gender, increasing age, normal BMI, low serum 25-hydroxyvitamin D, and pioglitazone use further increase the risk of osteoporosis.

BACKGROUND: Camurati-Engelmann disease (CED) is a rare bone dysplasia characterized by diffuse diaphyseal osteosclerosis. Skull base involvement in CED can result in hypopituitarism but is seldom reported. Our objective was to report a patient with acquired hypopituitarism due to CED and assess the management challenges. CASE REPORT: A 20-year-old boy presented with lower limb pain. He had walking difficulty in childhood, which was diagnosed as CED and managed with prednisolone. He later discontinued treatment and was lost to follow-up. Current re-evaluation showed short stature (-3.6 standard deviation), low weight (-4.3 standard deviation), and delayed puberty with delayed bone age (13 years). He was found to have secondary hypogonadism (luteinizing hormone level, 0.1 mIU/mL [1.7-8.6 mIU/mL]; follicle-stimulating hormone level, 1.0 mIU/mL [1.5-12.4 mIU/mL]; and testosterone level, 0.087 nmol/L [9-27 nmol/L]), growth hormone deficiency (low insulin-like growth factor I level, 120 ng/mL [226-903 ng/mL] and peak growth hormone level of 7 ng/mL on insulin-induced hypoglycemia), and secondary hypocortisolism (cortisol level, 105 nmol/L [170-550 nmol/L] and adrenocorticotropic hormone level, 6 pg/mL [5-65 pg/mL]). Serum prolactin level was normal (8.3 ng/mL [5-20 ng/mL]), and he was euthyroid on levothyroxine replacement. Magnetic resonance imaging revealed a partially empty sella. Sanger sequencing revealed a missense mutation (p.R218C/c.652C>T) in exon 4 of the TGFβ1 gene. The patient was treated with zoledronate, losartan, and oral prednisolone and continued on levothyroxine and testosterone replacement, which resulted in symptomatic improvement. DISCUSSION: The index case manifested severe CED requiring multimodality therapy. Later, he developed combined pituitary hormone deficiencies, which were managed with thyroid and gonadal hormone replacement with the continuation of glucocorticoids. The partial efficacy of bisphosphonates in CED has been reported in the literature. CONCLUSION: Skull base involvement in CED can lead to structural and functional hypopituitarism as a result of intracranial hypertension. ispartof: AACE Clin Case Rep vol:8 issue:2 pages:58-64 ispartof: location:United States status: Published online

Type 2 diabetes (T2D) is a well-known disease that impaired bone mechanical properties and increases the risk of fragility fracture. The bone tissue is a viscoelastic material that means the loading rate determines its mechanical properties. This study investigates the impact of T2D on the viscoelastic properties of human bone and its association with microstructure and biochemical properties.Viscoelasticity is an important mechanical property of bone and for this the interaction of individual constituents of bone plays an important role. The viscoelastic nature of bone can be affected by aging and diseases, which can further influence its deformation and damage behavior.The present study investigated the effects of T2D on the viscoelastic behavior of trabecular bone. The femoral heads of T2D (n = 26) and non-T2D (n = 40) individuals with hip fragility fractures were collected for this investigation. Following the micro-CT scanning of all bone samples, the stress relaxation and dynamic mechanical analysis (DMA) tests were performed to quantify the viscoelasticity of bone. Further, a correlation analysis was performed to investigate the effects of alteration in bone microstructural and biochemical parameters on viscoelasticity.The stress relaxation and frequency sweep responses of T2D and non-T2D trabecular bone specimens were not found significantly different. However, the storage modulus, initial stiffness, and initial stress were found lower in T2D bone. The significant correlation of percentage stress relaxed is obtained between the mineral content (r= - 0.52, p-value = 0.003), organic content (r = 0.40, p-value = 0.02), and mineral-to-matrix ratio (r = - 0.43, p-value = 0.009). Further, storage and loss modulus were correlated with bone volume fraction (BV/TV) for both groups. The stress relaxation and frequency sweep characteristics were not found significantly connected with the other chemical, structural, or clinical parameters.This study suggests that T2D does not affect the time-dependent response of human femoral trabecular bone. The viscoelastic properties are positively correlated with organic content and negatively correlated with mineral content.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by recalcitrant hypophosphatemia. Reports from the Indian subcontinent are scarce, with most being single center experiences involving few patients. Herein, we conducted a retrospective analysis of 30 patients of TIO diagnosed at three tertiary care hospitals in India. Patients with persistent hypophosphatemia (despite correction of hypovitaminosis D), normocalcemia, elevated alkaline phosphatase, low TmP/GFR and elevated or ‘inappropriately normal’ FGF23 levels were labeled as having TIO. They were sequentially subjected to functional followed by anatomical imaging. Patients with a well-localized tumor underwent excision; others were put on phosphorous and calcitriol supplementation. The mean age at presentation was 39.6 years with female:male ratio of 3:2. Bone pain (83.3%) and proximal myopathy (70%) were the chief complaints; 40% of cases had fractures. The mean delay in diagnosis was 3.8 years. Tumors were clinically detectable in four patients (13.3%). The mean serum phosphate was 0.50 mmol/L with a median serum FGF23 level of 518 RU/mL. Somatostatin receptor-based scintigraphy was found to be superior to FDG-PET in tumor localization. Lower extremities were the most common site of the tumor (72%). Tumor size was positively correlated with serum FGF23 levels. Twenty-two patients underwent tumor resection and 16 of them had phosphaturic mesenchymal tumors. Surgical excision led to cure in 72.7% of patients whereas disease persistence and disease recurrence were seen in 18.2% and 9.1% of cases, respectively. At the last follow-up, serum phosphate in the surgically treated group was significantly higher than in the medically managed group.

Long-term Type 2 Diabetes (T2D) affects the normal functioning of heart, kidneys, nerves, arteries, bones, and joints. The T2D gradually alters the intrinsic material properties, and structural integrity of the tissues and prolonged hyperglycemia causes chronic damages to these tissues quality. Clinically no such technique is available which can assess the altered tissues quality associated with T2D. In the present study, the microstructural characterization (surface morphology, surface roughness and density and calcium content), material characterization (modulus, hardness), and macromolecular characterization (disulfide bond content, protein content and its secondary structure) are investigated among healthy, diabetic controlled (DC) and uncontrolled diabetic (UC) group of fingernail plate. It is found that T2D has an adverse effect on the human fingernail plate quality. The parameters of nail plate quality are changing in a pattern among all the three groups. The properties mentioned above are degrading in DC group, but the degradation is even worst in the case of severity of T2D (UC group) as compared to the healthy group (Healthy

Background: Osteogenesis imperfecta (OI) is a genetic connective tissue disorder characterized by skeletal deformity and increased risk of fracture. Independent mobility is of concern for OI patients as it is associated with the quality of life. The present study investigates the variation of kinetic and kinematic gait parameters of type IV OI subjects and compares them with age-matched healthy subjects. Materials and Methods: Gait analysis is performed on five type IV OI patients and six age-matched normal subjects. Spatiotemporal, kinematic, and kinetic data are obtained using Helen Hayes marker placement protocol. Results: The results indicate an imprecise double-humped profile for vertical ground reaction force (GRF) with reduced ankle push off power and walking speed for OI subjects. Moreover, a comparison of vertical GRFs in OI subjects with that of healthy subjects suggests lower values for the former. The results encourage and motivate for further investigation with a bigger set of subjects. Conclusion: This information may be useful in developing a better understanding of pathological gait in type IV OI subjects, which ultimately helps the design of subject-specific implants, surgical preplanning, and rehabilitation.

Fibrogenesis imperfecta ossium (FIO) is a rare, metabolic bone disease clinically characterized by generalized bone pain and fragility fractures in both the axial and appendicular skeleton. The etiology of the disease is unknown and the pathogenesis is poorly understood. In this disorder, collagen arrangement in the bone is disorganized , and causes abnormalities in the organic bone matrix. Genetic cues causing this defect in collagen arrangement are largely undetermined. Microarray analysis showed remarkable changes in gene expression , when we compared gene expression of FIO with the control. Differential gene expression analysis revealed 50 gene signatures, which can be used to organize novel ways to diagnose and treat FIO patients.

Background: The research work endeavors to develop a liquid dosage form of an efficacious antipsoriatic drug, i.e., coal tar, but having problems like variability and patient noncompliance.Methods: The emulsion was prepared by the wet gum method from standardized coal tar. The optimized lotion obtained after sequential experimental designs was characterized for various dosage form and/or coal tar-related properties including efficacy.Results: The formulation deposited more coal tar in the unit area of rat skin than marketed lotions. The efficacy of lotion in psoriasis animal models was more or equivalent to marketed lotions. The formulation showed one compartment body model dermatokinetics, nonirritancy after repeated applications, and stability at room conditions for a year.Conclusion: The formulation with desired attributes was successfully developed.

Introduction Spondylo-epi-metaphyseal dysplasia (SEMD) represents a group of osteo-chondrodysplasias characterized by vertebral, epiphyseal as well as metaphyseal abnormalities. Several genes have been identified underlying the different forms. Methodology and results Two relatives (cousins) in a family were found to have disproportionate short stature with clinical and radiological features suggestive of SEMD. Metabolic bone profile was normal including parathyroid hormone and 25(OH)vitamin D3. Exome sequencing revealed a missense mutation (p. T120M) in the von-Willebrand factor A-domain of the Matrilin 3 (MATN3) gene that segregates with the disease in the family. Conclusion We identified a homozygous missense mutation in MATN3, an important structural component of the extracellular matrix of cartilage, as the genetic cause of SEMD in this pedigree. MATN3 mutations have been more commonly associated with multiple epiphyseal dysplasia than SEMD. Recognition of this mutation will aid in enhancing the understanding and expanding the spectrum of this particular skeletal dysplasia., Highlights • SEMD due to Matrilin-3 mutation is rare and needs further characterisation. • Infantile onset of disproportionate dwarfism and progressive bowing of knees and elbows are diagnostic clues. • Absence of extraskeletal features is noteworthy.

Fibrous dysplasia (FD) is a benign bone lesion characterized by replacement of normal bone with abnormal fibrous tissue, clinically manifesting as deformities, bone pains, and pathological fractures. The standard medical management for FD includes systemic bisphosphonate therapy. The efficacy of systemic bisphosphonate is however limited with minimal functional improvement and pain relief. Keeping the above lacunae in mind, we have made a solitary attempt at treating FD with locally administered zoledronic acid. A 25-year-old gentleman had presented to our institute with swelling and pain involving the left thigh and left lower leg. He was diagnosed as having polyostotic FD, confirmed on bone histopathology. He was administered 4 mg of zoledronic acid intravenously while 1 mg of the drug was injected locally into the femoral lesion under ultrasound and fluoroscopy guidance. There were no peri-procedural complications. At 6 months follow-up, there was marked improvement in pain scores at the left thigh, while that at the left leg remained unchanged. In addition, repeat bone scintigraphy showed a 20.8% and 25.3% reduction in anterior and posterior uptake values, respectively, at the left femur while that at the left tibia remained unaltered.

Fibrogenesis imperfecta ossium (FIO) is an extremely uncommon fatal bone disorder of poorly understood etiology. The pathogenesis of FIO is not well known. The fundamental skeletal defect appears to be an abnormality in organic matrix of bone characterized by defective mineralization of the abnormal collagen. FIO clinically manifests in middle-aged adults presenting with fracture and bone pain. Elevated serum alkaline phosphatase is the only and the most consistent biochemical abnormality. Although paraproteinemia is observed in one-third of cases, the pathogenic link to the disease process is unclear. Limited information on FIO and its close resemblance to many metabolic bone disorders leads to delayed or missed diagnoses and management. Prednisolone, bisphosphonates, melphalan and steroids have been tried previously with variable success. Recently, a trial of recombinant growth hormone therapy was found to be effective. Further research focused on the pathogenetic mechanisms of FIO is needed to identify and develop targeted therapeutic options.

Hypophosphatasia is an inborn error in metabolism characterized by low serum alkaline phosphatase (ALP) activity resulting from deactivating mutations in TNSALP (also known as ALPL), the gene that encodes the ‘tissue-specific’ isoenzyme of ALP. The disease exhibits significant clinical heterogeneity that spans from death in utero to only dental complications in adult life. Herein, we report a 47-year-old woman presenting with fracture of shaft of left femur. She had been complaining of pain in both of her thighs for the past 3 years. In addition, she gave a history of premature loss of teeth. Review of old radiographs revealed pseudo-fractures involving the lateral cortices of the femora on both sides. Biochemical panel revealed hyperphosphatemia, persistently low total alkaline phosphatase (ALP) and low-normal bone turnover markers. Screening of her siblings revealed low ALP in her younger sister and brother who were otherwise free from any major dento-arthro-osseous complaints. Sanger sequencing showed a novel, heterozygous, missense mutation in exon 5 at position 311 (c.311a > g;p.104 Asn > Ser) of ALPL gene in the three members. The patient underwent open reduction and intramedullary nailing of left femur along with prophylactic nailing on right side. This case report represents the first genetically confirmed kindred of adult hypophosphatasia from the Indian subcontinent.

Biodegradable porous polymeric scaffolds were prepared from Polyurethane (PU) for the purpose of osteoblast cells regeneration to utilize in the restoration of damage bone tissues. The PU was synthesized from post-consumer discarded Poly ethylene terephthalate (PET) waste by glycolysis method. The produced monomer bis(2-hydroxyethyl) terephthalate (BHET) was reacted with diisocynate and there after with selected chain extender glycol. In this study, graphene oxide (GO) was used as a polyol in the esterification reaction. Also, the GO acted as a nano filler that imparted the strength to the system along with antimicrobial activity. The various composites of PU-GO/hydroxyapatite (Hap) were prepared by varying the content of GO/Hap from 0 to 10% of total weight of the composite. The porous scaffolds were developed from composites by solvent casting/particulate leaching (SCPL) method. Furthermore, the physical, morphological, elemental, mechanical and thermo-mechanical properties of scaffolds were analyzed. The prepared scaffolds were subjected to U2OS human embryonic osteoblast cell line to analyze the response of osteoblast cells. In vitro studies such as cell growth, degradation, and cyto-compatibility were carried out. The outcomes of this study have asserted that the developed scaffolds are compatible for U2OS cells growth, thus can be used for bone tissue regeneration.

CONTEXT Fibrogenesis imperfecta ossium (FIO) is a rare and progressive skeletal bone disorder of undetermined etiology. Given its FIO, the pathogenesis of FIO remains elusive and no effective treatment exists. Based on review of all published cases and our collective experience of FIO, we offer a comprehensive approach for the diagnosis and management of this complex and fatal disorder. EVIDENCE ACQUISITION A review of electronic and print medical literature comprising case reports and articles retrieved from PubMed database up to March 2018 was conducted using the search term "fibrogenesis imperfecta". In addition, references from retrieved case reports and articles were screened for articles containing information on FIO and differential diagnoses. EVIDENCE SYNTHESIS Twenty-six articles containing information concerning twenty-nine cases were identified. We reviewed the clinical and pathophysiologic features of all published cases. Comprehensive information on FIO is lacking in the literature. Diagnostic approach, in an attempt to gain insight into the disease, differed depending on the advancements in science and tools available at the time of patient identification. The response to various treatments used has been widely variable. CONCLUSION The dearth of information on FIO and low index of suspicion may lead to delayed or missed diagnoses and management. The fundamental skeletal defect appears to be an abnormality in organic matrix of bone characterized by defective mineralization of the abnormal collagen. Research focused on the identification of pathogenetic factors is needed. Albeit, long-term outcomes of growth hormone therapy are yet to be ascertained, short-term effectiveness appears promising.

Background & objectives: Bisphosphonates (BPs) are the most widely prescribed medicines for the treatment of osteoporosis because of their efficacy and favourable safety profile. There have been, several reports on an increased incidence of atypical femoral fractures after long term treatment with BPs. The objective of this study was to evaluate the clinical presentation including prodromal symptoms, skeletal radiograph findings, type and duration of BPs received and treatment outcome of patients who developed atypical femoral fractures during bisphosphonate therapy. Methods: In this retrospective study, eight patients with atypical femoral fractures were analysed based on clinical features, biochemical and radiological investigations. Results: Of the eight patients, who sustained atypical femoral fractures, six were on alendronate and two were on zoledronate therapy before the fractures. In addition to BPs, two patients were on long term corticosteroid therapy for rheumatoid arthritis and Addison′s disease. Three patients had bilateral atypical femoral fractures. Except one, all of them had prodromal symptoms prior to fracture. Skeletal radiograph showed cortical thickening, pointed (beaking of) cortical margin and transverse fracture in meta-diaphyseal location. Serum calcium, phosphate, alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) concentrations were within the reference range in all patients. Interpretation & conclusions: Long term bisphosphonate therapy may increase the risk of atypical femoral fractures. Presence of prodromal pain, thickened cortex with cortical beaking may be an early clue for predicting the atypical fractures. High risk patients need periodical skeletal survey and a close follow up for early detection of cases.

Mumps is a vaccine-preventable disease that usually occurs as a self-limiting parotitis, but it can also lead to several life-threatening complications, including pancreatitis, meningitis, and encephalitis. The molecular epidemiology of the virus is poorly understood. The present study describes an outbreak of mumps virus infection in Punjab, India. The etiology was confirmed by serology and RNA detection to be mumps virus in 72 % of the cases and 50 % of contacts. This study, for the first time, revealed the mumps virus genotypes circulating in the Indian subcontinent as subtype G2 of genotype G.

Context: Fibrogenesis imperfecta ossium (FIO) is a rare bone disease manifested by generalized bone pain, fragility fractures, progressive disability, and extensive mineralization defect seen in bone biopsy specimens. The pathogenesis of the disease is unknown and currently there is no effective treatment. Objective: To report on the effect of recombinant human growth hormone (rhGH) therapy in FIO. Design: An observational study in two patients. Setting: Endocrinology clinic in an academic institution. Patients or Other Participants: Two siblings with FIO. Intervention(s): rhGH was administered subcutaneously at a dose of 1 U daily for 1 year. Main Outcome Measures: Changes in clinical, biochemical, radiological, and bone histological (i.e., light and transmission electron microscopy, and histomorphometry) investigations. Results: Except for an elevated serum alkaline phosphatase level, results of routine biochemical, hematological, and hormonal investigations were normal in both patients. Radiographs showed pseudofractures and bone scans revealed a "beheaded" tracer activity pattern (i.e., superscan without uptake in the skull). Bone biopsy specimens showed severe mineralization defect simulating osteomalacia with disorganized collagen fibril alignment. Treatment with rhGH was followed by clinical, biochemical, and radiological improvement in both the patients, with substantial improvement in the mineralization defect, most likely due to rhGH-induced improvement in collagen fibril arrangement. Conclusion: We report on two brothers with FIO and demonstrate clinical improvement and restoration of normal bone pathology with rhGH therapy. We suggest that rhGH is a potential therapy for FIO for which no effective therapy currently exists.

Wireless sensor networks consists of sensors nodes used for the communication purpose. Wireless sensor networks are self-organized and data-centric. In Wireless sensor networks, there are some issues like data redundancy, high energy conservation and injecting unnecessary data. Data aggregation method overcomes the data redundancy problem. In this paper, a data integrity protection strategy has been discussed based on watermarking technologies to protect the data integrity. At the end of the paper comparison of various schemes is also provided based on characteristics like the method adopted by each scheme and the position at which integrity is provided.

Camurati-Engelmann disease (CED, OMIM 131300), or progressive diaphyseal dysplasia, is a rare autosomal dominant skeletal dysplasia, caused by mutations in the transforming growth factor-beta 1 (TGF beta 1) gene. We describe the first Indian CED family with genetic confirmation and presenting manifestations. The proband is a 17-year-old woman who presented with lower limb pain and proximal muscle weakness. Skeletal radiographs of the long bones revealed cortical, periosteal, and endosteal thickenings, predominantly affecting the diaphyses of the long bones. On detailed evaluation, there was a strong family history of bone disorder with similar symptoms of pain and radiological findings in several family members. Exon sequencing of the TGF beta 1 gene was performed in available family members. Based on clinical and radiographic studies and its familial nature, a diagnosis of CED was made and confirmed by mutation analysis. A heterozygous G to A transition in exon 4 of the TGF beta 1 gene (R218H) was detected in 5 out of 10 available family members, including 4 affecteds and 1 asymptomatic individual. Many of our affected individuals responded to glucocorticoids and cortical windowing. CED is a rare genetic disease with variable clinical manifestations and incomplete penetrance. CED needs to be considered in the differential diagnosis of nonspecific limb pain and waddling gait in all young individuals.

Introduction Sclerosteosis (OMIM 269500 ) is a rare autosomal recessive condition characterized by increased bone density associated with syndactyly. It is linked to a genetic defect in the SOST gene coding for sclerostin. So far, six different loss-of-function mutations in SOST have been reported in patients with sclerosteosis. Our objective was to sequence and identify mutation in the SOST and LRP5 genes which are known to be causal for craniotubular hyperostosis in a patient from India. Patient and methods A 22 year old woman presented with typical features of sclerosteosis in form of progressive visual and hearing loss, syndactyly and radiographs revealing increased density of bone. Genomic sequencing of the SOST gene as well as exons 2, 3 and 4 of the LRP5 gene was performed. Results We identified a novel homozygous mutation in the SOST gene, characterized as one nucleotide insertion resulting in a frame shift mutation and loss of functional sclerostin. Her parents were also found to have a similar but heterozygous mutation in the SOST gene. Conclusion A novel frame shift mutation in the SOST gene causing loss of functional sclerostin was identified in a patient with sclerosteosis and her parents.

Introduction: Dengue is one of the most important arboviral infections caused by one of the four dengue serotypes, 1-4. Objective: To study the applicability of different diagnostic methods in diagnosis of dengue viral infection. Materials and Methods: A total of 2101 blood samples were collected for confirmation of dengue viral infection. All the samples were tested by dengue-specific IgM ELISA, of which 111 were also tested for NS1 antigen detection and 27 acute samples (≤5 days) were further subjected for viral RNA detection by RT-PCR and isolation in C6/36 cell line. To detect the sensitivity of NS1 antigen for different dengue virus serotypes, four dengue serotype 1 and 12 dengue 3 were subjected for the NS1 antigen assay. Results: Most common age group affected was 16-45 years, with male to female ratio of 2.8:1. During first 3 days of illness virus isolation and RT-PCR were the most sensitive (83%) followed by NS1 antigen detection (75%) and IgM detection (37.5%). The positivity of IgM detection was found to be significantly higher as compared to NS1 detection during 4 to 5 days and also after 5 days of illness (P < 0.05). Dengue serotypes 1 and 3 were found to be co-circulated, dengue 1 being the predominant serotype. Conclusion: Virus isolation and RT-PCR were the most sensitive tests during the early period of illness whereas beyond third day, IgM antibody detection was found to be the most sensitive method of dengue diagnosis.