Cost-effectiveness of FRAX®-based intervention thresholds for management of osteoporosis in Singaporean women.

Cost-effectiveness analysis of FRAX® intervention thresholds (ITs) in Singaporean women > 50 years of age showed that generic alendronate was cost-effective at age-dependent major osteoporotic fracture (MOF) IT from the ages of 65 years for both full and real-world adherence whilst hip fracture (HF) ITs were cost-effective from the ages of 60 and 65 years. Alendronate was cost-effective irrespective of age only at fixed MOF IT of 14% and HF IT of 3.5%. INTRODUCTION: FRAX®-based intervention thresholds (ITs) were recently identified for osteoporosis management in Singapore. This study aimed to assess the cost-effectiveness of ITs in Singaporean women over the age of 50 years. METHODS: A validated Markov microsimulation model was used to estimate the lifetime healthcare costs (SGD2019) per quality-adjusted life-years (QALY) of generic alendronate compared with no treatment. Cost-effectiveness of age-dependent FRAX® major osteoporotic fracture (MOF) and hip fracture (HF) ITs was explored. In addition, ITs that would lead to cost-effectiveness were computed. Fracture incidence and cost data were obtained from the Ministry of Health and a previously published Singaporean study. A cost-effectiveness threshold of SGD 62,500/QALY gained was used, based conservatively on 0.7 times the Singapore GDP per capita. RESULTS: Generic alendronate was shown to be cost-effective at MOF ITs from the ages of 65 years, while HF ITs were cost-effective from the ages of 60 and 65 years, assuming full and real-world adherence, respectively. A 14% MOF and a 3.5% HF ITs were required for alendronate to be cost-effective above 50 years. CONCLUSION: This study suggests that the treatment of Singaporean women with alendronate is cost-effective at age-dependant FRAX® intervention thresholds at 65 years and older. Furthermore, identifying women at any age above 50 years with a 10-year risk of MOF or HF of 14% or 3.5% would lead to efficient use of resources. Cost-effective access to therapy for patients at high fracture probability based on FRAX® could contribute to reduce the growing burden of osteoporotic fractures in Singapore.

Excess mortality after hip fracture: fracture or pre-fall comorbidity?

Comorbidity and hip fracture independently increased mortality risk for 9 years in both sexes, with a significant additive interaction in the first year among women and through 6 years among men. INTRODUCTION: Hip fracture is associated with a persistently elevated mortality risk, but it is unknown whether the elevated risk is due to the fracture or to pre-fracture comorbidity. METHODS: In a population-based study in Singapore with 9 years of follow-up, patients age > 50 with first hip fracture from 2008 to 2017 were pair-matched to a cohort without hip fracture by age, sex, ethnicity, and pre-fracture Charlson Comorbidity Index (CCI). We investigated additive interaction using the relative excess risk due to interaction (RERI) and multiplicative interaction using the ratio of relative risks. RESULTS: Twenty-two thousand five hundred ninety of 22,826 patients with a first hip fracture in 2008-2017 were successfully matched. Hip fracture and comorbidity independently increased mortality risk for 9 years in both sexes. After adjustment for comorbidity, excess mortality risk continued to persist for 9 years post-fracture in both men and women. Women with a hip fracture and pre-fracture CCI > 4 had a higher relative risk (RR) of mortality at 9 years of 3.29 [95% confidence interval (CI) 3.01, 3.59] than those without comorbidity (RR 1.51, 95%CI 1.36, 1.68) compared to the referent without hip fracture or comorbidity. An additive interaction between hip fracture and pre-fracture CCI > 4 was observed in the first post-fracture year` [relative excess risk due to interaction (RERI) 1.99, 95%CI 0.97, 3.01]. For men with CCI ≥ 4, the positive additive interaction was observed through 6 years. CONCLUSIONS: Excess mortality risks post-fracture are attributable to both the fracture and pre-fracture comorbidity. Early interventions in hip fracture patients with high comorbidity could reduce their excess mortality.

Hip fractures in Singapore: ethnic differences and temporal trends in the new millennium.

Despite an increase in absolute numbers, the age-standardized incidence of hip fractures in Singapore declined in the period 2000 to 2017. Among the three major ethnic groups, Chinese women had the highest fracture rates but were the only group to show a temporal decline. INTRODUCTION: A study published in 2001 predicted a 30-50% increase in Singapore hip fracture incidence rates over the ensuing 30 years. To test that prediction, we examined the incidence of hip fracture in Singapore from 2000 to 2017. METHODS: We carried out a population-based study of hip fractures among Singapore residents aged ≥ 50 years. National medical insurance claims data were used to identify admissions with a primary discharge diagnosis of hip fracture. Age-adjusted rates, based on the age distribution of the Singapore population of 2000, were analyzed separately by sex and ethnicity (Chinese, Malay, or Indian). RESULTS: Over the 18-year study period, 36,082 first hip fractures were recorded. Total hip fracture admissions increased from 1487 to 2729 fractures/year in the years 2000 to 2017. Despite this absolute increase, age-adjusted fracture rates declined, with an average annual change of - 4.3 (95% CI - 5.0, - 3.5) and - 1.1 (95% CI - 1.7, - 0.5) fractures/100,000/year for women and men respectively. Chinese women had 1.4- and 1.9-fold higher age-adjusted rates than Malay and Indian women: 264 (95% CI 260, 267) versus 185 (95% CI 176, 193) and 141 (95% CI 132, 150) fractures/100,000/year, respectively. Despite their higher fracture rates, Chinese women were the only ethnic group exhibiting a decline, most evident in those ≥ 85 years, in age-adjusted fracture rate of - 5.3 (95% CI - 6.0, - 4.5) fractures/100,000/year. CONCLUSION: Although the absolute number of fractures increased, steep drops in elderly Chinese women drove a reduction in overall age-adjusted hip fracture rates. Increases in the older population will lead to a rise in total number of hip fractures, requiring budgetary planning and new preventive strategies.

A novel heavy metal ATPase peptide from Prosopis juliflora is involved in metal uptake in yeast and tobacco.

Heavy metal pollution of agricultural soils is one of the most severe ecological problems in the world. Prosopis juliflora, a phreatophytic tree species, grows well in heavy metal laden industrial sites and is known to accumulate heavy metals. Heavy Metal ATPases (HMAs) are ATP driven heavy metal pumps that translocate heavy metals across biological membranes thus helping the plant in heavy metal tolerance and phytoremediation. In the present study we have isolated and characterized a novel 28.9 kDa heavy metal ATPase peptide (PjHMT) from P. juliflora which shows high similarity to the C-terminal region of P1B ATPase HMA1. It also shows the absence of the invariant signature sequence DKTGT, and the metal binding CPX motif but the presence of conserved regions like MVGEGINDAPAL (ATP binding consensus sequence), HEGGTLLVCLNS (metal binding domain) and MLTGD, GEGIND and HEGG motifs which play important roles in metal transport or ATP binding. PjHMT, was found to be upregulated under cadmium and zinc stress. Heterologous expression of PjHMT in yeast showed a higher accumulation and tolerance of heavy metals in yeast. Further, transgenic tobacco plants constitutively expressing PjHMT also showed increased accumulation and tolerance to cadmium. Thus, this study suggests that the transport peptide from P. juliflora may have an important role in Cd uptake and thus in phytoremediation.

Diffuse optical spectroscopic imaging of subcutaneous adipose tissue metabolic changes during weight loss.

BACKGROUND: Changes in subcutaneous adipose tissue (AT) structure and metabolism have been shown to correlate with the development of obesity and related metabolic disorders. Measurements of AT physiology could provide new insight into metabolic disease progression and response to therapy. An emerging functional imaging technology, diffuse optical spectroscopic imaging (DOSI), was used to obtain quantitative measures of near infrared (NIR) AT optical and physiological properties. METHODS: Ten overweight or obese adults were assessed during 3 months on calorie-restricted diets. DOSI-derived tissue concentrations of hemoglobin, water and lipid and the wavelength-dependent scattering amplitude (A) and slope (b) obtained from 30 abdominal locations and three time points (T0, T6, T12) were calculated and analyzed using linear mixed-effects models and were also used to form 3D surface images. RESULTS: Subjects lost a mean of 11.7±3.4% of starting weight, while significant changes in A (+0.23±0.04 mm(-1), adj. P<0.001),b (-0.17±0.04, adj. P<0.001), tissue water fraction (+7.2±1.1%, adj. P<0.001) and deoxyhemoglobin (1.1±0.3 µM, adj. P<0.001) were observed using mixed-effect model analysis. DISCUSSION: Optical scattering signals reveal alterations in tissue structure that possibly correlate with reductions in adipose cell volume, while water and hemoglobin dynamics suggest improved AT perfusion and oxygen extraction. These results suggest that DOSI measurements of NIR optical and physiological properties could be used to enhance understanding of the role of AT in metabolic disorders and provide new strategies for diagnostic monitoring of obesity and weight loss.

Identification of Lasiodiplodia species inciting stem rot of dragon fruit in India through polyphasic approach.

Lasiodiplodia species commonly thrive as endophytes, saprobes, and plant pathogens in tropical and subtropical regions. Association of Lasiodiplodia species causing stem rot in dragon fruit in the coastal belt of Odisha, eastern India, has been illustrated here. The stem rot disease was characterized by yellowing of the stem, followed by softening of the stem tissues with fungal fructifications of the pathogen in the affected tissues. On the basis of macro- and micromorphological characteristics, the four fungal isolates recovered from diseased stems were identified initially as Lasiodiplodia species. By comparing DNA sequences within the NCBI GenBank database as well as performing a multigene phylogenetic analysis involving the internal transcribed spacer region (ITS-rDNA), ß-tubulin (ß-tub), and elongation factor-alpha (EF1-α) genes, the identity of Lasiodiplodia isolates was determined. The isolate CHES-21-DFCA was identified as Lasiodiplodia iraniensis (syn: L. iranensis) and the remaining three isolates, namely CHES-22-DFCA-1, CHES-22-DFCA-2, and CHES-22-DFCA-3, as L. theobromae. Although pathogenicity studies confirmed both L. iraniensis and L. theobromae were responsible for stem rot in dragon fruit, L. iraniensis was more virulent than L. theobromae. This study established the association of Lasiodiplodia species with stem rot in dragon fruit using a polyphasic approach. Further investigations are required, particularly related to on host-pathogen-weather interaction and spatiotemporal distribution across the major dragon fruit-growing areas of the country to formulate prospective disease management strategies. This is the first report on these two species of Lasiodiplodia inflicting stem rot in Hylocereus species in India.

A MYB transcription factor from the grey mangrove is induced by stress and confers NaCl tolerance in tobacco.

MYB transcription factor genes play important roles in developmental and various other processes in plants. In this study, functional characterization of AmMYB1, a single-repeat MYB transcription factor isolated from the salt-tolerant mangrove tree Avicennia marina is reported. AmMYB1 cDNA was 1046 bp in length with an open reading frame of 783 bp, encoding 260 amino acids. The corresponding gene had two introns and three exons and was present as a single copy in A. marina. The deduced amino acid sequence showed similarities to MYB proteins reported in other plants, including the conserved MYB binding domain. RNA gel blot analysis showed that the AmMYB1 transcript expression was more pronounced in green photosynthetic tissue and was strongly induced by stresses such as salt (500 mM), light (500 µE m(-2) s(-1)), and the exogenous application of ABA (100 µM). An analysis of the upstream sequence of AmMYB1 gene revealed the presence of regulatory elements identical to those present in the promoters of stress inducible genes. The promoter was responsive to NaCl and could enhance reporter gene expression in planta. An in vitro DNA binding assay using the promoter region (TGGTTAG) of the AtRD22 gene and a transactivation assay in yeast cells suggest the possibility of AmMYB1 protein regulating the expression of other genes during salt stress. Transgenic tobacco plants constitutively expressing the AmMYB1 transcription factor showed better tolerance to NaCl stress.

In-Hospital Mortality following Proximal Femur Fractures in Elderly Population.

Context In India, hip fracture crude incidence above the age of 50 years was 129 per 100,000. Aims The aim of this study is to analyze the in-hospital mortality following proximal femur fractures in elderly Indian population. Methods and Material The study was done in Sri Ramachandra Medical Center, Chennai, India. Patient's records were retrospectively evaluated for a period of 3 years from January 1, 2015 to January 1, 2018. The inclusion criteria were patients both male and female aged more than 65 years admitted with the diagnosis of neck of femur or intertrochanteric or subtrochanteric fractures. The exclusion criteria were patients having any associated fracture or previous hip fracture history or diagnosed primary or secondary malignancies. To evaluate any surgical delay two groups were formed. After eliminating cases based on exclusion criteria, we had 270 patients for evaluation. Statistical Analysis Used The collected data were analyzed with IBM.SPSS statistics software 23.0 Version. To describe about the data descriptive statistics frequency analysis, percentage analysis were used for categorical variables and the mean and standard deviation (SD) were used for continuous variables. To find the significant difference between the bivariate samples, Student's t -test and analysis of variance (ANOVA) were used. The p -value of 0.05 is considered as significant level. Results We had a total of 24 mortalities with 15 males and 9 females. The in-hospital mortality of patients who underwent replacement surgeries for proximal femur fractures was 14 in our study. Sixteen of the in-hospital mortality patients had low Parker's mobility score. Twenty patients had mortality when surgery was delayed more than 48 hours. Conclusions In-hospital mortality in elderly patients having proximal femur fracture increases significantly if the patient was having low-preoperative mobility status, if surgery was delayed more than 48 hours, and if patient undergoes replacement surgeries.

Transcript level characterization of a cDNA encoding stress regulated NAC transcription factor in the mangrove plant Avicennia marina.

NAC transcription factors are a family of functionally diverse proteins responsive to biotic and abiotic stresses. A full-length cDNA isolated from the salt stressed mangrove plant Avicennia marina showed high sequence identity to NAC proteins induced upon biotic stress in tomato and potato. The predicted protein sequence had all the highly conserved sub domains characteristic of NAC domain containing proteins. Northern analysis for AmNAC1 expression under tolerable (250 mM) concentration of NaCl revealed up regulation of the transcript after 48 h and higher transcript level after 10 days of treatment. Induction of AmNAC1 after 12h of ABA treatment was similar to the treatment with stressful (500 mM) concentration of NaCl. The results suggest the involvement of AmNAC1 in early salt stress response and long-term adjustment to salt, besides a role for ABA in its expression under salt stress conditions.

Antibacterial and toxicity evaluation of C-phycocyanin and cell extract of filamentous freshwater cyanobacterium-Westiellopsis sps.

In this study the culture filtrate and C-phycocyanin obtained from filamentous fresh water cyanobacterium Westiellopsis sps were tested for their antibacterial activity against three different bacterial cultures: Bacillus subtilis, Pseudomonas sps and Xanthomonas sps. The growth of all bacterial strains tested was inhibited by the culture filtrate and C-phycocyanin. The diameter of inhibition zones varied from 1.3 to 13.2 mm and from 2.2 to 13.1 mm for the culture filtrate and C-phycocyanin, respectively. It is therefore suggested that extracts from the Westiellopsis sps could be used traditionally in the treatment of bacterial infections. Bioassay studies of silkworm showed that there was no symptom of ill health after feeding the phycocyanin treated leaves and the body weight and silk gland weight of the silkworm increased with range of 65.0-102.6 mg and 209-240 mg respectively compared to the control.

Neuropathic Knee Joint - A Complication of Syrinx Following Spinal Anesthesia: A Rare Case Report and Review of Literature.

INTRODUCTION: Neurological complications due to spinal anesthesia are dysesthesia, paresthesia, cauda equina syndrome, and neuropathic joint. However, neurological complications are rare. We report a case of neuropathic joint of knee as a complication of syrinx following postspinal anesthesia. CASE REPORT: A 33-year-old female came with complaints of pain and instability of her left knee and left foot drop. She had developed weakness of her left lower limb following her cesarean section surgery done under spinal anesthesia. Clinically and radiologically, she had features of the neuropathic left knee joint which had occurred as a complication of syrinx following spinal anesthesia. CONCLUSION: The case is reported for its rarity and to highlight the possible neurological complications of spinal anesthesia.

The stone women-Myositis ossificans Progressiva.

INTRODUCTION: Myositis ossificans progressiva is very rare with a worldwide prevalence of approximately 1 case in 2 million individuals. No ethnic, racial, or geographic predisposition has been described. Although familial forms inherited on a dominant autosomal basis have been described, most cases are sporadic. CASE REPORT: 16 yr female came to opd with complaints of progressive restriction of movements of bilateral elbow, bilateral shoulder, bilateral knee and bilateral hip for past 4 years. On examination patient is found to have short great toes of bilateral foot and ffd of all the joints. Patient is bed ridden and had acute pain for past 2 wks. Patient was evaluated and diagnosed to have myositis ossificans progressiva. Patient was treated with short course of steroids and bisphosphonates. Patient's pain improved and the patient was discharged on request as she was not willing for further management. CONCLUSION: Myositis ossificans progressiva is a rare disease with limited treatment options. At present there is no available treatment to completely cure the disease. Short course of steroids and bisphosphonates helps to relieve symptoms of acute pain.

Urethral polyp presenting as interlabial mass in young girls.

We describe two young girls who presented with an interlabial mass. Histologic examination of each excised mass revealed a benign urethral polyp covered with transitional and squamous epithelium. Urethral polyps should be included in the differential diagnosis of an interlabial mass in young female patients.

Gastric wall necrosis in an HIV-positive patient.

Perforation of the gastrointestinal tract is rare in HIV infection and occurs most often in the colon and small intestine. Gastric perforation in HIV-positive patients has not been reported so far. We report an HIV-positive patient who developed gastric perforation.

Gene expression analysis of volatile-rich male flowers of dioecious Pandanus fascicularis using expressed sequence tags.

Pandanus fascicularis is dioecious with the female plant producing a non-scented fruit while the male produces a flower rich in volatiles. The essential oil extracted from the flowers is economically exploited as a natural flavouring agent as well as for its therapeutic properties. Molecular dissection of this distinct flower for identifying the genes responsible for its aroma by way of expressed sequence tags (ESTs) has not been initiated in spite of its economic viability. A male flower-specific cDNA library was constructed and 977 ESTs were generated. CAP3 analysis performed on the dataset revealed 83 contigs (549 ESTs) and 428 singlets, thereby yielding a total of 511 unigenes. Functional annotation using the BLAST2GO software resulted in 1952 Gene ontology (GO) functional classification terms for 621 sequences. Unknown proteins were further analysed with InterProScan to determine their functional motifs. RNA gel blot analysis of 26 functionally distinct transcripts potentially involved in flowering and volatile generation, using vegetative and reproductive tissues of both the sexes, revealed differential expression profiles. In addition to an overview of genes expressed, candidate genes with expression that are modulated predominantly in the male inflorescence were also identified. This is the first report on generation of ESTs to determine the subset of genes that can be used as potential candidates for future attempts aimed towards its genetic and genome analysis including metabolic engineering of floral volatiles in this economically important plant.

Characterization of a triglyceride hydrolase secreted by canine liver maintained in vitro.

These studies demonstrate that canine liver synthesizes a TGH activated by C-I but not by C-II. This TGH has properties similar to lipoprotein lipase C-I isolated from postheparin plasma of human subjects, but differs from a previously reported liver triglyceride-lipase or protamine insensitive-lipase in its sensitivity to NaCl and protamine sulfate, as well as in its requirement for a serum cofactor, C-I. These data suggest the possiblity that, in dogs, liver is a source of plasma LPLC-I.

Magnetic resonance imaging of a seminal vesicle cyst and a review of the imaging modalities.

Magnetic resonance imaging (MRI) is invaluable in the diagnosis of pelvic pathology as demonstrated here by its use in the diagnosis of a seminal vesicle cyst. Comparison is made with computed tomography, ultrasonography and voiding cystourethrography (VCUG). MRI provides precise, anatomical detail, far superior to other modalities. The advantages and disadvantages of older diagnostic modalities, such as intravenous pyelogram, VCUG and seminal vesiculography, are discussed in this article.