Open tibial fracture with severe soft tissue injury and bone loss managed with ipsilateral fibular transport and its complications: a case report

Massive segmental bone defects of tibia present as a challenging task to manage specially when associated with extensive soft tissue injury. A 30 year old male presented to Paras HMRI hospital, Patna, post road traffic accident with Gustilo Anderson 3B comminuted open tibia shaft fracture and with an external fixator in situ with a grossly inflamed and infected wound. Initially patient was managed with serial wound debridement and skin grafting was done early to obtain adequate soft tissue coverage. The patient then underwent application of Ilizarov external fixator with plan of one level fibular osteotomy for ipsilateral fibular transport. With good outcome of the procedure clinically and radiologically, Ilizarov fixator was removed after time duration of about 1.3 years and limb was immobilized in plaster of Paris (POP) cast which was removed after 8 weeks. Within 1 month of removal of POP cast the patient presented to hospital again with complaints of pain and instability when his leg was run over by his child’s bicycle while playing. Diagnosed as fracture of proximal (transported) fibula he was managed then with locking plates; one of which was used as an internal fixator and the other as external fixator which was outside the body and acted as a support to the operated limb. After about 1 year the external locking plate was removed and patient was able to bear weight on his extremities. Despite various modalities to treat massive tibial gap, fibular transport procedure with Ilizarov external fixator seems to be the most viable option

Chronic patellofemoral instability and pain treated effectively by anteromedial tibial tubercle transfer (Fulkerson osteotomy) with or without medial patellofemoral ligament reconstruction

Background-Chronic patellar instability (subluxation and dislocation) and pain is a debilitating knee condition that frequently involves young, active patients. Bony malalignment and soft tissue injury (torn or stretched MPFL) is considered as a surgical indication for distal realignment in the form of Anteromedial tibial tubercle transfer(Fulkerson osteotomy) with or without MPFL reconstruction that effectively prevents the patella from tracking laterally and thus unloads the lateral patella while making the patellofemoral joint more congruous , stable and pain free.Materials and method - It is a prospective study of 22 patients of chronic patellar instability and pain. Follow up ranged from 24 to 36(average 30) months. Preoperative assessment included clinical examination, Lysholm, IKDC score and Radiological examination (X-ray, CT scan and MRI). 18 patients with history of dislocation and pain having bony malalignment and torn MPFL were treated with Fulkerson osteotomy and MPFL reconstruction and 4 patients with history of subluxation and pain having bony malalignment only were treated with Fulkerson osteotomy alone. Patients were followed up with the help of X-rays at regular interval and the clinical outcome was measured using scoring system. Results-There was a significant improvement in postoperative assessment with regards to scoring system (Lysholm and IKDC) and knee pain. Union at osteotomy site for all patients was seen. None of the patients had further episode of dislocation or subluxation. Pain at femoral site of MPFL reconstruction in 2 cases persisted for 3 months followed by resolution of their symptoms. One of our patients had profuse swelling at the site of operation postoperatively which was treated with Rest, Ice Pack, Compression and Limb elevation. Out of 22 patients undertaken infection at osteotomy site was seen in 1 patient for which implant removal was done from osteotomy site after union. Conclusion-Anteromedial Tibial tuberosity osteotomy and MPFL reconstruction is a successful procedure to treat patellofemoral pain and instability

Lentiviral Mediated Transgenesis by In Vivo Manipulation of Spermatogonial Stem Cells

This report describes a technique for the generation of transgenic mice by in vivo manipulation of spermatogonial stem cells with a high rate of success. Spermatogonial stem cells (SSCs) in pre-pubescent animals were infected in vivo with recombinant lentiviruses expressing EGFP-f and mated with normal females. All male pre-founder mice produced transgenic pups with an overall success rate of over 60%. The transgene was heritable and the pre-founder mice could be used in multiple mating experiments. This technology could be used to perform overexpression/knockdown screens in vivo using bar-coded lentiviruses, thus permitting the design of genetic screens in the mouse. Further, this technology could be adapted to other laboratory animals resulting in the generation of model systems that closely approximate human development and disease

Conceptualizing pathways linking women's empowerment and prematurity in developing countries.

BackgroundGlobally, prematurity is the leading cause of death in children under the age of 5. Many efforts have focused on clinical approaches to improve the survival of premature babies. There is a need, however, to explore psychosocial, sociocultural, economic, and other factors as potential mechanisms to reduce the burden of prematurity. Women's empowerment may be a catalyst for moving the needle in this direction. The goal of this paper is to examine links between women's empowerment and prematurity in developing settings. We propose a conceptual model that shows pathways by which women's empowerment can affect prematurity and review and summarize the literature supporting the relationships we posit. We also suggest future directions for research on women's empowerment and prematurity.MethodsThe key words we used for empowerment in the search were "empowerment," "women's status," "autonomy," and "decision-making," and for prematurity we used "preterm," "premature," and "prematurity." We did not use date, language, and regional restrictions. The search was done in PubMed, Population Information Online (POPLINE), and Web of Science. We selected intervening factors-factors that could potentially mediate the relationship between empowerment and prematurity-based on reviews of the risk factors and interventions to address prematurity and the determinants of those factors.ResultsThere is limited evidence supporting a direct link between women's empowerment and prematurity. However, there is evidence linking several dimensions of empowerment to factors known to be associated with prematurity and outcomes for premature babies. Our review of the literature shows that women's empowerment may reduce prematurity by (1) preventing early marriage and promoting family planning, which will delay age at first pregnancy and increase interpregnancy intervals; (2) improving women's nutritional status; (3) reducing domestic violence and other stressors to improve psychological health; and (4) improving access to and receipt of recommended health services during pregnancy and delivery to help prevent prematurity and improve survival of premature babies.ConclusionsWomen's empowerment is an important distal factor that affects prematurity through several intervening factors. Improving women's empowerment will help prevent prematurity and improve survival of preterm babies. Research to empirically show the links between women's empowerment and prematurity is however needed

A Novel Modular Antigen Delivery System for Immuno Targeting of Human 6-sulfo LacNAc-Positive Blood Dendritic Cells (SlanDCs)

Previously, we identified a major myeloid-derived proinflammatory subpopulation of human blood dendritic cells which we termed slanDCs (e.g. Schäkel et al. (2006) Immunity 24, 767-777). The slan epitope is an O-linked sugar modification (6-sulfo LacNAc, slan) of P-selectin glycoprotein ligand-1 (PSGL-1). As slanDCs can induce neoantigen-specific CD4+ T cells and tumor-reactive CD8+ cytotoxic T cells, they appear as promising targets for an in vivo delivery of antigens for vaccination. However, tools for delivery of antigens to slanDCs were not available until now. Moreover, it is unknown whether or not antigens delivered via the slan epitope can be taken up, properly processed and presented by slanDCs to T cells.Single chain fragment variables were prepared from presently available decavalent monoclonal anti-slan IgM antibodies but failed to bind to slanDCs. Therefore, a novel multivalent anti-slanDC scaffold was developed which consists of two components: (i) a single chain bispecific recombinant diabody (scBsDb) that is directed on the one hand to the slan epitope and on the other hand to a novel peptide epitope tag, and (ii) modular (antigen-containing) linker peptides that are flanked at both their termini with at least one peptide epitope tag. Delivery of a Tetanus Toxin-derived antigen to slanDCs via such a scBsDb/antigen scaffold allowed us to recall autologous Tetanus-specific memory T cells.In summary our data show that (i) the slan epitope can be used for delivery of antigens to this class of human-specific DCs, and (ii) antigens bound to the slan epitope can be taken up by slanDCs, processed and presented to T cells. Consequently, our novel modular scaffold system may be useful for the development of human vaccines

Adjuvant Properties of Thermal Component of Hyperthermia Enhanced Transdermal Immunization: Effect on Dendritic Cells

Hyperthermia enhanced transdermal (HET) immunization is a novel needle free immunization strategy employing application of antigen along with mild local hyperthermia (42°C) to intact skin resulting in detectable antigen specific Ig in serum. In the present study, we investigated the adjuvant effect of thermal component of HET immunization in terms of maturation of dendritic cells and its implication on the quality of the immune outcome in terms of antibody production upon HET immunization with tetanus toxoid (TT). We have shown that in vitro hyperthermia exposure at 42°C for 30 minutes up regulates the surface expression of maturation markers on bone marrow derived DCs. This observation correlated in vivo with an increased and accelerated expression of maturation markers on DCs in the draining lymph node upon HET immunization in mice. This effect was found to be independent of the antigen delivered and depends only on the thermal component of HET immunization. In vitro hyperthermia also led to enhanced capacity to stimulate CD4+ T cells in allo MLR and promotes the secretion of IL-10 by BMDCs, suggesting a potential for Th2 skewing of T cell response. HET immunization also induced a systemic T cell response to TT, as suggested by proliferation of splenocytes from immunized animal upon in vitro stimulation by TT. Exposure to heat during primary immunization led to generation of mainly IgG class of antibodies upon boosting, similar to the use of conventional alum adjuvant, thus highlighting the adjuvant potential of heat during HET immunization. Lastly, we have shown that mice immunized by tetanus toxoid using HET route exhibited protection against challenge with a lethal dose of tetanus toxin. Thus, in addition to being a painless, needle free delivery system it also has an immune modulatory potential

Global Three-Neutrino Vacuum Oscillation fits to the Solar and Atmospheric Anomalies

We determine the three-neutrino mixing and mass parameters that are allowed by the solar and atmospheric neutrino data when vacuum oscillations are responsible for both phenomena. The global fit does not appreciably change the allowed regions for the parameters obtained from effective two-neutrino fits. We discuss how measurements of the solar electron energy spectrum below 6.5 GeV in Super-Kamiokande and seasonal variations in the Super-Kamiokande, $^{71}$Ga, and BOREXINO experiments can distinguish the different solar vacuum solutions.Comment: Revtex, 31 pages, uses epsf.sty, 14 postscript figures. Version to be published in Phys. Rev.

Is Paromomycin an Effective and Safe Treatment against Cutaneous Leishmaniasis? A Meta-Analysis of 14 Randomized Controlled Trials

Millions of people worldwide are suffering from cutaneous leishmaniasis that is caused by parasites of the genus Leishmania. Although pentavalent antimony compounds are the treatment of choice, their use is limited by high cost, poor compliance, and systemic toxicity. Paromomycin was developed to overcome such limitations. However, there is no consensus on its efficacy. This meta-analysis assessed the efficacy and safety of paromomycin compared with placebo and pentavalent antimony compounds. Fourteen randomized controlled trials, including 1,221 patients, met our selection criteria. Topical paromomycin appeared to have therapeutic activity against the old world and new world cutaneous leishmaniasis, with increased local reactions, when combined with methylbenzethonium chloride. Topical paromomycin was not significantly different from intralesional pentavalent antimony compounds in treating the old world form, whereas it was inferior to parenteral pentavalent antimony compounds in treating the new world form. However, a similar efficacy was found between parenteral paromomycin and pentavalent antimony compounds in treating the new world form. Fewer systemic side effects were observed with topical and parenteral paromomycin than pentavalent antimony compounds. These results suggest that topical paromomycin with methylbenzethonium chloride could be a therapeutic alternative to pentavalent antimony compounds for selected cases of the old world cutaneous leishmaniasis

Longitudinal association between motor and obsessive compulsive symptoms in patients with psychosis and their unaffected siblings

Little is known about the co-prevalence of obsessive compulsive symptoms (OCS) and motor symptoms in patients with psychotic disorders. Cross-sectional associations between OCS and motor symptoms were assessed at baseline and at 3years follow-up in patients (n=726) with psychotic disorders and in their unaffected siblings (n=761) from the Dutch Genetic Risk and Outcome of Psychosis (GROUP) study. Furthermore, longitudinal associations between changes in OCS and motor symptoms were evaluated. At baseline, OCS was not associated with any motor symptom (akathisia, dyskinesia, parkinsonism or dystonia) in patients. At follow-up, patients with OCS reported significantly more akathisia. Dividing the patients into four groupsno OCS, OCS remission with OCS only at baseline, OCS de novo with OCS only at follow-up and a persistent OCS grouprevealed that the OCS de novo group already reported more akathisia at baseline compared to the no-OCS group. At follow-up, both the OCS de novo and the persistent OCS group reported more akathisia. These results remained significant after correcting for relevant confounders clozapine, GAF score, PANSS-negative score and IQ. Motor symptoms at baseline were significantly associated with OCS at follow-up, but not the other way around. In siblings, OCS at baseline was associated with akathisia, but this association was lost at follow-up. Results suggest that motor symptoms might precede co-occurring OCS in patients with psychotic disorders. However, no inference can be made about causality, and further prospective research is needed to investigate this assumption