Effect of oral nutritional supplements on outcomes in children presenting with, or at risk of, faltering growth in clinical settings: A systematic review and meta-analysis.

This systematic review summarises evidence regarding oral nutritional supplement (ONS) use in children with, or at risk of, faltering growth (FG). Ten randomised controlled trials (RCTs), compared changes in outcomes amongst children receiving ONS versus control were included. Overall, 1116 children (weighted mean (WM) age 5 years; n658 (59%) male) were recruited, of which 585 (52%) received ONS (WM intake contribution 412 kcal, 16.3 g protein, 395 ml) for 116 days (WM). ONS use was associated with significantly greater gains in weight (mean difference (MD) 0.4 kg, 95% CI [0.36, 0.44]) and height (MD 0.3 cm, 95% CI [0.03, 0.57]), likely related to improvements in nutritional intake. Mean compliance to prescribed dose was 98%. Data suggested an association between ONS use and reduced infections. Further research is warranted to establish ONS dosage and effects upon other outcomes. This review provides evidence to support use of ONS in the management of children with, or at risk of, FG.

Transmission blocking potency and immunogenicity of a plant-produced Pvs25-based subunit vaccine against Plasmodium vivax.

Malaria transmission blocking (TB) vaccines (TBVs) directed against proteins expressed on the sexual stages of Plasmodium parasites are a potentially effective means to reduce transmission. Antibodies induced by TBVs block parasite development in the mosquito, and thus inhibit transmission to further human hosts. The ookinete surface protein P25 is a primary target for TBV development. Recently, transient expression in plants using hybrid viral vectors has demonstrated potential as a strategy for cost-effective and scalable production of recombinant vaccines. Using a plant virus-based expression system, we produced recombinant P25 protein of Plasmodium vivax (Pvs25) in Nicotiana benthamiana fused to a modified lichenase carrier protein. This candidate vaccine, Pvs25-FhCMB, was purified, characterized and evaluated for immunogenicity and efficacy using multiple adjuvants in a transgenic rodent model. An in vivo TB effect of up to a 65% reduction in intensity and 54% reduction in prevalence was observed using Abisco-100 adjuvant. The ability of this immunogen to induce a TB response was additionally combined with heterologous prime-boost vaccination with viral vectors expressing Pvs25. Significant blockade was observed when combining both platforms, achieving a 74% and 68% reduction in intensity and prevalence, respectively. This observation was confirmed by direct membrane feeding on field P. vivax samples, resulting in reductions in intensity/prevalence of 85.3% and 25.5%. These data demonstrate the potential of this vaccine candidate and support the feasibility of expressing Plasmodium antigens in a plant-based system for the production of TBVs, while demonstrating the potential advantages of combining multiple vaccine delivery systems to maximize efficacy.

The Plasmodium berghei sexual stage antigen PSOP12 induces anti-malarial transmission blocking immunity both in vivo and in vitro.

Anti-malarial transmission-blocking vaccines (TBVs) aim to inhibit the transmission of Plasmodium from humans to mosquitoes by targeting the sexual/ookinete stages of the parasite. Successful use of such interventions will subsequently result in reduced cases of malarial infection within a human population, leading to local elimination. There are currently only five lead TBV candidates under examination. There is a consequent need to identify novel antigens to allow the formulation of new potent TBVs. Here we describe the design and evaluation of a potential TBV (BDES-PbPSOP12) targeting Plasmodium berghei PSOP12 based on the baculovirus dual expression system (BDES), enabling expression of antigens on the surface of viral particles and within infected mammalian cells. In silico studies have previously suggested that PSOP12 (Putative Secreted Ookinete Protein 12) is expressed within the sexual stages of the parasite (gametocytes, gametes and ookinetes), and is a member of the previously characterized 6-Cys family of plasmodial proteins. We demonstrate that PSOP12 is expressed within the sexual/ookinete forms of the parasite, and that sera obtained from mice immunized with BDES-PbPSOP12 can recognize the surface of the male and female gametes, and the ookinete stages of the parasite. Immunization of mice with BDES-PbPSOP12 confers modest but significant transmission-blocking activity in vivo by active immunization (53.1% reduction in oocyst intensity, 10.9% reduction in oocyst prevalence). Further assessment of transmission-blocking potency ex vivo shows a dose-dependent response, with up to a 76.4% reduction in intensity and a 47.2% reduction in prevalence observed. Our data indicates that PSOP12 in Plasmodium spp. could be a potential new TBV target candidate, and that further experimentation to examine the protein within human malaria parasites would be logical.

Lead clinical and preclinical antimalarial drugs can significantly reduce sporozoite transmission to vertebrate populations.

To achieve malarial elimination, we must employ interventions that reduce the exposure of human populations to infectious mosquitoes. To this end, numerous antimalarial drugs are under assessment in a variety of transmission-blocking assays which fail to measure the single crucial criteria of a successful intervention, namely impact on case incidence within a vertebrate population (reduction in reproductive number/effect size). Consequently, any reduction in new infections due to drug treatment (and how this may be influenced by differing transmission settings) is not currently examined, limiting the translation of any findings. We describe the use of a laboratory population model to assess how individual antimalarial drugs can impact the number of secondary Plasmodium berghei infections over a cycle of transmission. We examine the impact of multiple clinical and preclinical drugs on both insect and vertebrate populations at multiple transmission settings. Both primaquine (>6 mg/kg of body weight) and NITD609 (8.1 mg/kg) have significant impacts across multiple transmission settings, but artemether and lumefantrine (57 and 11.8 mg/kg), OZ439 (6.5 mg/kg), and primaquine (<1.25 mg/kg) demonstrated potent efficacy only at lower-transmission settings. While directly demonstrating the impact of antimalarial drug treatment on vertebrate populations, we additionally calculate effect size for each treatment, allowing for head-to-head comparison of the potential impact of individual drugs within epidemiologically relevant settings, supporting their usage within elimination campaigns.

Transmission-blocking interventions eliminate malaria from laboratory populations.

Transmission-blocking interventions aim to reduce the prevalence of infection in endemic communities by targeting Plasmodium within the insect host. Although many studies have reported the successful reduction of infection in the mosquito vector, direct evidence that there is an onward reduction in infection in the vertebrate host is lacking. Here we report the first experiments using a population, transmission-based study of Plasmodium berghei in Anopheles stephensi to assess the impact of a transmission-blocking drug upon both insect and host populations over multiple transmission cycles. We demonstrate that the selected transmission-blocking intervention, which inhibits transmission from vertebrate to insect by only 32%, reduces the basic reproduction number of the parasite by 20%, and in our model system can eliminate Plasmodium from mosquito and mouse populations at low transmission intensities. These findings clearly demonstrate that use of transmission-blocking interventions alone can eliminate Plasmodium from a vertebrate population, and have significant implications for the future design and implementation of transmission-blocking interventions within the field.

Optically Excited Entangled States in Organic Molecules Illuminate the Dark.

We utilize quantum entangled photons to carry out nonlinear optical spectroscopy in organic molecules with an extremely small number of photons. For the first time, fluorescence is reported as a result of entangled photon absorption in organic nonlinear optical molecules. Selectivity of the entangled photon absorption process is also observed and a theoretical model of this process is provided. Through these experiments and theoretical modeling it is found that while some molecules may not have strong classical nonlinear optical properties due to their excitation pathways; these same excitation pathways may enhance the entangled photon processes. It is found that the opposite is also true. Some materials with weak classical nonlinear optical effects may exhibit strong non-classical nonlinear optical effects. Our entangled photon fluorescence results provide the first steps in realizing and demonstrating the viability of entangled two-photon microscopy, remote sensing, and optical communications.

Potential biomarkers of temporomandibular joint disorders.

PURPOSE: The purpose of this study was to identify protein markers present in subjects with temporomandibular joint disorders (TMDs) and clicking compared with the levels in controls. MATERIALS AND METHODS: This was a pilot case-control study, and we report the preliminary results. Samples of joint aspirate collected from patients with TMDs and controls who had undergone surgery for a problem other than TMDs were analyzed using isobaric tags for relative and absolute quantitation (iTRAQ) and biotin-labeled-based protein arrays. The data obtained from these techniques were used to identify the proteins of interest, which were then quantitated using enzyme-linked immunosorbent assay (ELISA). The patient samples studied included joint aspirate collected clinically from the controls and patients and included samples from both the right and the left sides of each patient with a TMD. RESULTS: The 8 TMJ aspirate samples from 6 subjects included 5 aspirate samples from 4 patients and 3 from 2 controls. The greatest standardized protein concentration of endocrine gland-derived vascular endothelial growth factor/prokineticin-1 (EG-VEGF/PK1) and D6 was found in both joints of the controls compared with the levels from the joints of the patients. With 1 exception, the standardized protein concentration was significantly lower in the patients than in the controls. The lower levels of EG-VEGF/PK1 and D6 in the patients compared with the controls suggest that these cytokines might be possible biomarkers for TMDs. CONCLUSION: In the present pilot study, greater levels of EG-VEGF/PK1 and D6 were found in the controls than in the patients with TMDs. Proteomic analysis of the proteins present in the diseased joints compared with those in the controls might help to identify proteins present when pain or degeneration of the joint occurs. The proteomic information might be useful in the development of future therapies.

Management of dystonia of the lateral pterygoid muscle with botulinum toxin A.

Oromandibular dystonia (OMD) is a rare neurological condition infrequently seen by oral and maxillofacial surgeons which may result in inappropriate deviation of the mandible, subluxation and intraoral soft tissue trauma. A case is presented of a patient suffering from spasmodic torticollis and lateral pterygoid dystonia and currently under treatment with botulinum A toxin (Botox) injections. Botox has emerged as the most effective form of symptomatic treatment for abnormabilities in muscle movement, namely dystonia with oromandibular symptoms.

Analysis of the collagen I and fibronectin of temporomandibular joint synovial fluid and discs.

PURPOSE: The objective of this study was to investigate the content of synovial fluid aspirates and temporomandibular joint (TMJ) disc tissue for collagen I and total fibronectin in patients with closed lock. Fibronectin contains dual properties of assisting with wound healing and inducing cartilage degradation. Native fibronectin has been shown to assist with wound repair, whereas particular fibronectin fragments may degrade cartilage. In addition, collagen I is the major supporting protein of the TMJ disc and will degrade as osteoarthritis progresses. Fibronectin or collagen I expression in human TMJ synovial aspirates and disc tissue may indicate the proteins' involvement in closed lock. The hypothesis of this study is that TMJ discs and serum of patients with closed lock will contain an increased amount of fibronectin and decreased amount of collagen I. MATERIALS AND METHODS: We analyzed a total of 8 diseased TMJ discs and 4 diseased synovial fluid aspirates. For our control samples, we assessed 5 synovial samples from healthy patients and control skin samples. Using an enzyme-linked immunosorbent assay allowed us to measure the total amount of fibronectin and collagen I in synovial aspirates. Furthermore, we used light microscopy to assess TMJ disc histology and collagen architecture in control skin samples. Lastly, using fluorescent staining, we examined fibronectin and collagen I expression in TMJ discs. We compared the fluorescent staining and light microscopy results of both proteins within each disc to confirm fibronectin and collagen I expression. RESULTS: Disc specimens with advanced morphologic pathology showed significant labeling for fibronectin in 3 of 3 cases and for collagen I in 4 of 4 cases. There was no considerable difference in detection of either fibronectin or collagen I in TMJ synovial aspirates from patients with advanced disc pathology compared with controls. CONCLUSIONS: The levels of fibronectin and collagen I in the TMJ disc and synovial fluid may be influenced by the stage of disease. The results did not provide a clear understanding of fibronectin and collagen I involvement with tissue repair in closed-lock cases. Detection of fibronectin fragments may provide more meaningful results.

Limitation of the diagnostic value of MR images for diagnosing temporomandibular joint disorders.

OBJECTIVES: Many studies have shown that MRI findings are reliable when experienced calibrated observers work as a group. The hypothesis was that MRI findings can be used as the gold standard also when evaluation is made by single expert observers. STUDY DESIGN: Temporomandibular joint (TMJ) MRIs of 34 patients were evaluated independently by four reviewers with expert knowledge of radiology for the presence of 13 specified pathologic entities, as well as the quality of the images, on a 5-step scale from "Sure Yes" to "Sure No". Intraclass correlation coefficients were calculated to estimate the rating reliability of the examiners. A coefficient of at least 0.8 was deemed good, between 0.60 and 0.80 was deemed acceptable, and less than 0.60 was considered poor. Additionally, weighted kappa statistics were used for pair-wise comparisons across all four reviewers. RESULTS: The hypothesis was not supported by the results. None of the 13 correlation coefficients for comparisons between single examiner evaluations of pathologic entities was good and 8 were poor. CONCLUSION: A diagnosis of TMD based on MRI examination protocols made by a single examiner should not be accepted as a gold standard with regard to TMJ disorders.

The incidence of tinnitus in people with disorders of the temporomandibular joint.

This study was conducted to compare the prevalence of tinnitus in the general population with its incidence in people with dysfunction of the temporomandibular joint (TMJD) within the temporomandibular disorder (TMD) population. Earlier studies had indicated the prevalence of tinnitus in the general population to be in the range of 10-14%. Between 1981 and 1990, analysis of 989 consecutive TMJD patients from a TMD database found the incidence of tinnitus to be 7.28% (72 patients). In addition, no statistical difference was found between the occurrence of tinnitus in men and women. Thirty-nine patients of the tinnitus group (54.17%) claimed to have pain in the ear as compared to 318 patients (32.15%) in the total population. No patient with tinnitus claimed to have decreased hearing, whereas three patients (0.30% of the total population) complained of a decrease in hearing.

Comparison of the postsurgical stability of the Le Fort I osteotomy using 2- and 4-plate fixation.

PURPOSE: This study was conducted to evaluate the postoperative stability of Le Fort I osteotomies accomplished with 2-plate versus 4-plate fixation. METHODS: This is a retrospective study involving 32 patients who underwent Le Fort I 1-piece osteotomy concurrent with orthodontic therapy. All patients were treated by 1 attending surgeon during an 18-month period. Sixteen patients were treated by plate and screw fixation consisting of 4 miniplates (group I), and an additional 16 patients were treated using 2 miniplates (group II). In group I, fixation was accomplished with 2.0-mm low-profile Lorenz (Walter Lorenz Surgical Inc, Jacksonville, FL) plates and screws placed at the piriform aperture and at the maxillary buttress. Four screws were placed in each of the plates. In group II, fixation was accomplished with 2.0-mm low-profile Lorenz plates and screws placed at the piriform aperture. Again, 4 screws were placed in each of the plates. RESULTS: Serial cephalometric evaluation at arbitrary anterior nasal spine and posterior nasal spine for both groups showed that postoperative skeletal changes in the direction of the surgical movement were seen in approximately 20% of cases; these changes averaged less than 1 mm. Postoperative skeletal changes opposite to the direction of the surgical movement were seen in approximately 30% of cases; these changes also averaged less than 1 mm. No postoperative skeletal changes were seen in approximately 50% of cases. For all measured changes about arbitrary anterior nasal spine and posterior nasal spine, there was no significant difference between groups I and II. CONCLUSION: This study suggested that postoperative skeletal changes associated with the use of 2-plate fixation do not appear to differ significantly from those seen with 4-plate fixation.

Serotonin receptor activation enhances neurite outgrowth of thalamic neurones in rodents.

Serotonin (5-HT) has been shown to influence the development of the rodent barrel field by affecting the patterning of thalamic axons in the somatic sensory cortex. To determine whether this is a direct effect on thalamocortical neurones, we analyzed primary thalamic cultures taken from E15 mouse embryos. We show that 5-HT enhances neurite outgrowth of thalamic neurones. The sodium channel blocker, TTX, blocks these effects, whereas the selective 5-HT1B agonist CGS-12066A maleate reproduced 5-HT's effect. Using PCR and immunocytochemistry, we found that 5-HT1B receptors are already expressed by thalamic neurones at E15, and that this expression is maintained in vitro. These results suggest that 5-HT-1B receptor activation directly affects the growth of thalamocortical axons.

Rat basophilic leukaemia (RBL) cells overexpressing Rab3a have a reversible block in antigen-stimulated exocytosis.

The rat basophilic leukaemia (RBL) cell line has been widely used as a convenient model system to study regulated secretion in mast cells. Activation of these cells through the high-affinity receptor for IgE (Fcepsilon-RI) results in degranulation and the extracellular release of mediators. There is good evidence of a role for GTPases in mast cell degranulation, and a number of studies with peptides derived from the Rab3a effector domain have suggested that Rab3a may function in this process. However, in neuroendocrine cells, overexpression of Rab3a can act as a negative regulator of stimulated exocytosis [Holz, Brondyk, Senter, Kuizon and Macara (1994) J. Biol. Chem. 269, 10229-10234; Johanes, Lledo, Roa, Vincent, Henry and Darchen (1994) EMBO J. 13, 2029-2037]. In order to study the function of Rab3a in RBL degranulation, we have generated clones of RBL cells stably expressing Rab3a, and show that in these haematopoietic cells Rab3a can also function as a negative regulator of exocytosis. Overexpression of a mutant form of Rab3a (Asn-135 to Ile), which is predicted to be predominantly GTP-bound, also inhibited degranulation. However, overexpression of a mutant form of Rab3a that was truncated at the C-terminus to remove the sites for geranylgeranylation failed to inhibit degranulation. The effect of Rab3a is specific to secretion, and we observe no effect of Rab3a on receptor-mediated endocytosis. The Rab3a-induced block in degranulation can be bypassed by stimulation of streptolysin-O-permeabilized cells with guanosine 5'-[gamma-thio]triphosphate. We conclude from these studies that Rab3a is implicated in an early stage of granule targeting, whereas fusion of granules with the plasma membrane is regulated by a distinct downstream GTP-binding protein or proteins.

Immunocytochemical analysis of axonal outgrowth in synaptotagmin mutations.

Synaptotagmin is a synaptic vesicle specific protein that binds calcium and phospholipids in vitro and is required for calcium-regulated fusion of synaptic vesicles with the presynaptic membrane. We have examined the possible requirement for synaptotagmin in axonal outgrowth by following neuronal development in Drosophila embryos deficient for the synaptotagmin gene. We find that synaptotagmin is expressed abundantly in axons and growth cones before synapse formation in wild-type embryos. Using antibodies to the intravesicular domain of synaptotagmin to label live embryos, we demonstrate that vesicle populations containing synaptotagmin actively undergo exocytosis during axonogenesis. We have used immunocytochemical techniques to examine the distribution of the axonal protein Fasciclin II, the presynaptic membrane protein syntaxin, and the synaptic vesicle protein cysteine string protein, in synaptotagmin null mutations. The distribution of these proteins is similar in wild-type and synaptotagmin mutant embryos, suggesting that synaptotagmin is not required for axonogenesis in the CNS or PNS. Based on these findings, we suggest that the molecular mechanisms underlying vesicular-mediated membrane expansion during axonal outgrowth are distinct from those required for synaptic vesicle fusion during neurotransmitter release.

Telling about the analyst's pregnancy.

Pregnancy is one of several events in the life of an analyst which may affect an analysis, calling for special technical considerations. For the analyst, this exception to the tenet of anonymity, along with countertransference guilt, narcissistic preoccupation, heightened infantile conflicts, and intense patient responses, may stimulate anxiety that becomes focused on the timing and manner of informing the patient. For the patient, preoccupation with the timing of the telling may serve as a displacement from other meanings of the pregnancy. Candidate analysts may face particular difficulties managing the impact of their pregnancies on control cases. We address practical and technical considerations in telling, the transference and counter-transference surrounding it, ethical concerns, and the challenges of supervising a pregnant candidate.

Double-gloving and the incidence of perforations during specific oral and maxillofacial surgical procedures.

The concerns of surgeons about effective means of barrier protection during surgery is increasing owing to concern about the human immunodeficiency virus (HIV). There are various oral and maxillofacial surgical procedures that require the use of sharp instruments, and the oral and maxillofacial surgeon may be at risk for contamination due to possible perforation of the surgical gloves when manipulating these instruments. This study evaluated the incidence of perforations when performing specific oral and maxillofacial surgical procedures when double-gloving barrier protection was used. It found an increased incidence of perforations when performing procedures that required the use of sharp instruments in comparison with those procedures that did not require the use of such instruments.