A prospective study on surgical fixation of complex supracondylar femur fracture with distal femoral locking compression plate: our experiences at a tertiary care centre

Background: The optimal treatment of complex supracondylar femur fractures remains always challenging and controversial. the purpose of this prospective study was to evaluate the efficacy of distal femoral locking compression plate (DF-LCP) in terms of functional outcome and union rate for highly unstable complex supracondylar femur fractures and to determine the influencing factors of an unfavourable outcome.Methods: After obtaining approval from institutional ethics committee, 45 patients with complex supracondylar femur fractures were managed by open reduction and internal fixation with DF-LCP through lateral approach and as per standard protocol. The follow-up results were analysed clinically and radiologically, using the “Schatzker and Lambert criteria” at once in a month for first three months, once in three months up to one year and once in six months thereafter up to 2 years post-operatively.Results: In the present study, average duration of radiological union was 16 (range 12-22) weeks. The average range of motion of knee joint was 105 degrees. Out of 45 patients, clinical results were excellent in 48.9%, good in 17.8%, fair in 22.2% and poor in 11.1% patients according to Schatzker and Lambert criteria. Knee stiffness (7 cases), secondary arthritis (5 cases), and non-union (4 cases) were the main complications observed in this study, which were treated accordingly.Conclusions: DF-LCP holds the metaphyseal bone strongly and prevents metaphyseal collapse and mal-rotation in complex or highly unstable supracondylar femur fractures and simultaneously, it provides stable fixation to promote fracture union and allows early rehabilitation with acceptable complications

Comparative analysis of emm type pattern of Group A Streptococcus throat and skin isolates from India and their association with closely related SIC, a streptococcal virulence factor

<p>Abstract</p> <p>Background</p> <p>Group A streptococcus (GAS) causes a wide variety of life threatening diseases in humans and the incidence of such infections is high in developing countries like India. Although distribution of <it>emm </it>types of GAS in India has been described, there is a lack of data describing either the comparative distribution of <it>emm </it>types in throat versus skin isolates, or the distribution of certain virulence factors amongst these isolates. Therefore in the present study we have monitored the <it>emm </it>type pattern of Group A streptococcus throat and skin isolates from India. Additionally, the association of these isolates with closely related <it>sic </it>(<it>crs</it>), a multifunctional compliment binding virulence factor, was also explored.</p> <p>Results</p> <p>Of the 94 (46 throat and 48 skin) isolates analyzed, 37 <it>emm </it>types were identified. The most frequently observed <it>emm </it>types were <it>emm</it>49 (8.5%) and <it>emm</it>112 (7.5%) followed by 6.5% each of <it>emm</it>1-2, <it>emm</it>75, <it>emm</it>77, and <it>emm</it>81. Out of 37 <it>emm </it>types, 27 have been previously reported and rest were isolated for the first time in the Indian Community. The predominant <it>emm </it>types of throat (<it>emm</it>49 and <it>emm</it>75) samples were different from those of skin (<it>emm</it>44, <it>emm</it>81 and <it>emm</it>112) samples. After screening all the 94 isolates, the <it>crs </it>gene was found in six <it>emm</it>1-2 (<it>crs</it>1-2) isolates, which was confirmed by DNA sequencing and expression analysis. Despite the polymorphic nature of <it>crs</it>, no intravariation was observed within <it>crs</it>1-2. However, insertions and deletions of highly variable sizes were noticed in comparison to CRS isolated from other <it>emm </it>types (<it>emm</it>1.0, <it>emm</it>57). CRS1-2 showed maximum homology with CRS57, but the genomic location of <it>crs</it>1-2 was found to be the same as that of <it>sic</it>1.0. Further, among <it>crs </it>positive isolates, <it>spe</it>A was only present in skin samples thus suggesting possible role of <it>spe</it>A in tissue tropism.</p> <p>Conclusion</p> <p>Despite the diversity in <it>emm </it>type pattern of throat and skin isolates, no significant association between <it>emm </it>type and source of isolation was observed. The finding that the <it>crs </it>gene is highly conserved even in two different variants of <it>emm</it>1-2 GAS (<it>spe</it>A +ve and -ve) suggests a single allele of <it>crs </it>may be prevalent in the highly diverse throat and skin isolates of GAS in India.</p

Immune response against M protein-conserved region peptides from prevalent group A Streptococcus in a North Indian population

BackgroundGroup A streptococci (GAS) cause infections with a high prevalence in most developing countries. A GAS vaccine under trial that is based on the amino-terminus of the M protein provides type-specific immunity, and hence seems ineffective in India because of heterogeneous emm types. However, the conserved C-terminal region of the M protein protects against multiple serotypes. In this paper, the immune response generated against the conserved C-repeat region of the M protein was checked in an Indian population to establish their vaccine candidature.MethodsWhen screened for GAS, patients with pharyngitis, rheumatic fever/rheumatic heart disease (RF/RHD), and invasive disease showed heterogeneous emm types, out of which five prevalent types (1-2, 11, 49, 75 and 112) were selected for the study. The C-terminal region of their M proteins showed conserved C1-, C2-, and C3-repeats. The C1-repeat was more diverse and had two different J14-like sequences. Peptides to these C-terminal regions (J14.1 and J14-R6) were designed. Antibodies against these peptides were analyzed using the sera of 130 GAS-infected volunteers.ResultsSerum antibodies were significantly higher in patients with acute rheumatic fever, RHD, and invasive disease than in patients with pharyngitis or the healthy controls. The serum antibodies to these peptides was higher in teenagers and adults than in children.ConclusionResults showed an association between streptococcal disease progression and the age-related development of immunity to the conserved regions. Hence, these peptides could be considered protective in impeding streptococcal infections worldwide

Microbiological Spectrum of Brain Abscess at a Tertiary Care Hospital in South India: 24-Year Data and Review

Intracranial abscesses are life-threatening infections that pose a diagnostic challenge not only to the neurosurgeon but also to the microbiologists. Detailed studies documenting the spectrum of infecting agents involved in brain abscesses are limited from India. Materials and Methods. This is a retrospective analysis of 352 samples from 1987 to 2010 analyzed at a tertiary care hospital in South India from 1987 to 2010, to document the changing trends with time. Results. The age of the patients ranged from 2 to 80 years, a larger number of males being affected. Otogenic infections were the most common cause while cryptogenic abscesses were 20%. Gram stain and culture positivity were 78% each. Gram-positive and negative facultative aerobes and obligate anaerobes were also on the rise. Unusual organisms, like Burkholderia pseudomallei, Salmonella typhi, Nocardia species, Cladosporium bantiana, Fonsecaea pedrosoi, Entamoeba histolytica, and Acanthamoeba were also isolated and/or detected from the brain abscesses aspirate or resected tissue. Summary. New and emerging pathogens associated with brain abscess, especially in immunosuppressed individuals, have renewed the necessity of an early detection, and it will be of great value in appropriate management of patients with brain abscess

Dissecting the functional role of polyketide synthases in Dictyostelium discoideum

Dictyostelium discoideum exhibits the largest repository of polyketide synthase (PKS) proteins of all known genomes. However, the functional relevance of these proteins in the biology of this organism remains largely obscure. On the basis of computational, biochemical, and gene expression studies, we propose that the multifunctional Dictyostelium PKS (DiPKS) protein DiPKS1 could be involved in the biosynthesis of the differentiation regulating factor 4-methyl-5-pentylbenzene-1,3-diol (MPBD). Our cell-free reconstitution studies of a novel acyl carrier protein Type III PKS didomain from DiPKS1 revealed a crucial role of protein-protein interactions in determining the final biosynthetic product. Whereas the Type III PKS domain by itself primarily produces acyl pyrones, the presence of the interacting acyl carrier protein domain modulates the catalytic activity to produce the alkyl resorcinol scaffold of MPBD. Furthermore, we have characterized an O-methyltransferase (OMT12) from Dictyostelium with the capability to modify this resorcinol ring to synthesize a variant of MPBD. We propose that such a modification in vivo could in fact provide subtle variations in biological function and specificity. In addition, we have performed systematic computational analysis of 45 multidomain PKSs, which revealed several unique features in DiPKS proteins. Our studies provide a new perspective in understanding mechanisms by which metabolic diversity could be generated by combining existing functional scaffolds

Clinical Findings and Pro-Inflammatory Cytokines in Dengue Patients in Western India: A Facility-Based Study

BACKGROUND: Descriptions of dengue immunopathogenesis have largely relied on data from South-east Asia and America, while India is poorly represented. This study characterizes dengue cases from Pune, Western India, with respect to clinical profile and pro-inflammatory cytokines. METHODOLOGY/PRINCIPAL FINDINGS: In 2005, 372 clinically suspected dengue cases were tested by MAC-ELISA and RT-PCR for dengue virus (DENV) aetiology. The clinical profile was recorded at the hospital. Circulating levels of IFN-gamma, TNF-alpha, IL-6, and IL-8 were assessed by ELISA and secondary infections were defined by IgM to IgG ratio. Statistical analysis was carried out using the SPSS 11.0 version. Of the 372 individuals, 221 were confirmed to be dengue cases. Three serotypes, DENV-1, 2 and 3 were co-circulating and one case of dual infection was identified. Of 221 cases, 159 presented with Dengue fever (DF) and 62 with Dengue hemorrhagic fever (DHF) of which six had severe DHF and one died of shock. There was a strong association of rash, abdominal pain and conjunctival congestion with DHF. Levels of IFN-gamma were higher in DF whereas IL-6 and IL-8 were higher in DHF cases (p<0.05). The mean levels of the three cytokines were higher in secondary compared to primary infections. Levels of IFN-gamma and IL-8 were higher in early samples collected 2-5 days after onset than late samples collected 6-15 days after onset. IFN-gamma showed significant decreasing time trend (p = 0.005) and IL-8 levels showed increasing trend towards significance in DHF cases (interaction p = 0.059). There was a significant association of IL-8 levels with thrombocytopenia and both IFN-gamma and IL-8 were positively associated with alanine transaminase levels. CONCLUSIONS/SIGNIFICANCE: Rash, abdominal pain and conjunctival congestion could be prognostic symptoms for DHF. High levels of IL-6 and IL-8 were shown to associate with DHF. The time trend of IFN-gamma and IL-8 levels had greater significance than absolute values in DHF pathogenesis

Potent New Small-Molecule Inhibitor of Botulinum Neurotoxin Serotype A Endopeptidase Developed by Synthesis-Based Computer-Aided Molecular Design

Botulinum neurotoxin serotype A (BoNTA) causes a life-threatening neuroparalytic disease known as botulism. Current treatment for post exposure of BoNTA uses antibodies that are effective in neutralizing the extracellular toxin to prevent further intoxication but generally cannot rescue already intoxicated neurons. Effective small-molecule inhibitors of BoNTA endopeptidase (BoNTAe) are desirable because such inhibitors potentially can neutralize the intracellular BoNTA and offer complementary treatment for botulism. Previously we reported a serotype-selective, small-molecule BoNTAe inhibitor with a Kiapp value of 3.8±0.8 µM. This inhibitor was developed by lead identification using virtual screening followed by computer-aided optimization of a lead with an IC50 value of 100 µM. However, it was difficult to further improve the lead from micromolar to even high nanomolar potency due to the unusually large enzyme-substrate interface of BoNTAe. The enzyme-substrate interface area of 4,840 Å2 for BoNTAe is about four times larger than the typical protein-protein interface area of 750–1,500 Å2. Inhibitors must carry several functional groups to block the unusually large interface of BoNTAe, and syntheses of such inhibitors are therefore time-consuming and expensive. Herein we report the development of a serotype-selective, small-molecule, and competitive inhibitor of BoNTAe with a Ki value of 760±170 nM using synthesis-based computer-aided molecular design (SBCAMD). This new approach accounts the practicality and efficiency of inhibitor synthesis in addition to binding affinity and selectivity. We also report a three-dimensional model of BoNTAe in complex with the new inhibitor and the dynamics of the complex predicted by multiple molecular dynamics simulations, and discuss further structural optimization to achieve better in vivo efficacy in neutralizing BoNTA than those of our early micromolar leads. This work provides new insight into structural modification of known small-molecule BoNTAe inhibitors. It also demonstrates that SBCAMD is capable of improving potency of an inhibitor lead by nearly one order of magnitude, even for BoNTAe as one of the most challenging protein targets. The results are insightful for developing effective small-molecule inhibitors of protein targets with large active sites

Children’s and adolescents’ rising animal-source food intakes in 1990–2018 were impacted by age, region, parental education and urbanicity

Animal-source foods (ASF) provide nutrition for children and adolescents’ physical and cognitive development. Here, we use data from the Global Dietary Database and Bayesian hierarchical models to quantify global, regional and national ASF intakes between 1990 and 2018 by age group across 185 countries, representing 93% of the world’s child population. Mean ASF intake was 1.9 servings per day, representing 16% of children consuming at least three daily servings. Intake was similar between boys and girls, but higher among urban children with educated parents. Consumption varied by age from 0.6 at <1 year to 2.5 servings per day at 15–19 years. Between 1990 and 2018, mean ASF intake increased by 0.5 servings per week, with increases in all regions except sub-Saharan Africa. In 2018, total ASF consumption was highest in Russia, Brazil, Mexico and Turkey, and lowest in Uganda, India, Kenya and Bangladesh. These findings can inform policy to address malnutrition through targeted ASF consumption programmes.publishedVersio

Incident type 2 diabetes attributable to suboptimal diet in 184 countries

The global burden of diet-attributable type 2 diabetes (T2D) is not well established. This risk assessment model estimated T2D incidence among adults attributable to direct and body weight-mediated effects of 11 dietary factors in 184 countries in 1990 and 2018. In 2018, suboptimal intake of these dietary factors was estimated to be attributable to 14.1 million (95% uncertainty interval (UI), 13.8–14.4 million) incident T2D cases, representing 70.3% (68.8–71.8%) of new cases globally. Largest T2D burdens were attributable to insufficient whole-grain intake (26.1% (25.0–27.1%)), excess refined rice and wheat intake (24.6% (22.3–27.2%)) and excess processed meat intake (20.3% (18.3–23.5%)). Across regions, highest proportional burdens were in central and eastern Europe and central Asia (85.6% (83.4–87.7%)) and Latin America and the Caribbean (81.8% (80.1–83.4%)); and lowest proportional burdens were in South Asia (55.4% (52.1–60.7%)). Proportions of diet-attributable T2D were generally larger in men than in women and were inversely correlated with age. Diet-attributable T2D was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, central and eastern Europe and central Asia, where burdens were larger in rural residents and in lower educated individuals. Compared with 1990, global diet-attributable T2D increased by 2.6 absolute percentage points (8.6 million more cases) in 2018, with variation in these trends by world region and dietary factor. These findings inform nutritional priorities and clinical and public health planning to improve dietary quality and reduce T2D globally.publishedVersio