Multi-site phosphorylation of the protein tyrosine phosphatase, PTP1B: identification of cell cycle regulated and phorbol ester stimulated sites of phosphorylation.
The non-transmembrane protein tyrosine phosphatase, PTP1B, comprises 435 amino acids, of which the C-terminal 114 residues have been implicated in controlling both localization and function of this enzyme. Inspection of the sequence of the C-terminal segment reveals a number of potential sites of phosphorylation. We show that PTP1B is phosphorylated on seryl residues in vivo. Increased phosphorylation of PTP1B is seen to accompany the transition from G2 to M phase of the cell cycle. Two major tryptic phosphopeptides appear in two-dimensional maps of PTP1B from mitotic cells. One of these comigrates with the peptide generated following phosphorylation of PTP1B in vitro at Ser386 by the mitotic protein Ser/Thr kinase p34cdc2:cyclin B. The site of phosphorylation that is responsible for the pronounced retardation in the electrophoretic mobility of PTP1B from mitotic cells has been identified by site directed mutagenesis as Ser352. The identify of the kinase responsible for this modification is presently unknown. We also show that stimulation of HeLa cells with the phorbol ester TPA enhances phosphorylation of PTP1B. Two dimensional phosphopeptide mapping reveals that the bulk of the phosphate is in a single tryptic peptide. The site, identified as Ser378, is also the site of phosphorylation by protein kinase C (PKC) in vitro. Thus the TPA-stimulated phosphorylation of PTP1B in vivo appears to result directly from phosphorylation by PKC. The effect of phosphorylation on the activity of PTP1B has been examined in immunoprecipitates from TPA-treated and nocodazole-arrested cells. TPA treatment does not appear to affect activity directly, whereas the activity of PTP1B from nocodazole-arrested cells is only 70% of that from asynchronous populations.


The chemotactic attraction of human fibroblasts to a lymphocyte-derived factor.
A quantitative assay that measures fibroblast chemotaxis in vitro is described. Application of this technique has revealed that peripheral blood lymphocytes stimulated by antigen or mitogen in vitro produce a factor that is chemotactic for human dermal fibroblasts. This lymphocyte-derived chemotactic factor for fibroblasts (LDCF-F) is different from the lymphokine that is chemotactic for monocytes or macrophages. Macrophages are required for the generation of LDCF-F by T lymphocytes stimulated by phytohemagglutinin. The fibroblast chemotactic factor is heat stable (56 degrees C for 30 min), trypsin sensitive, and neuraminidase resistant. LDCF-F could function to attact connective tissue fibroblasts to sites at which cell-mediated immune reactions are occurring in vivo.


Moving regional health services planning and management to a population-based approach: implementation of the Regional Operating Model (ROM) in Victoria, Australia.
Various jurisdictions are moving towards population-based approaches to plan and manage healthcare services. The evidence on the implementation of these models remains limited. The aim of this study is to evaluate the effect of a regional operating model (ROM) on internal functioning and stakeholder engagement of a regional office. Semi-structured interviews and focus groups with staff members and stakeholders of the North West Metropolitan Regional office in Victoria, Australia, were conducted. Overall, the ROM was perceived as relevant to staff and stakeholders. However, creating shared objectives and priorities across a range of organisations remained a challenge. Area-based planning and management is seen as simplifying management of contracts; however, reservations were expressed about moving from specialist to more generalist approaches. A clearer articulation of the knowledge, skills and competencies required by staff would further support the implementation of the model. The ROM provides a platform for public services and stakeholders to discuss, negotiate and deliver on shared outcomes at the regional level. It provides an integrated managerial platform to improve service delivery and avoid narrow programmatic approaches.


Oral health-related quality of life after prosthetic rehabilitation in patients with oral cancer: A longitudinal study with the Liverpool Oral Rehabilitation Questionnaire version 3 and Oral Health Impact Profile-14 questionnaire.
Prosthodontic rehabilitation helps to improve the oral health-related quality of life (OHRQOL). The Liverpool Oral Rehabilitation Questionnaire (LORQ) and Oral Health Impact Profile (OHIP) are specific tools that measure OHRQOL. The primary objective of this study was to assess the impact of oral rehabilitation on patients' OHRQOL following treatment for cancer of oral cavity using LORQ version 3 (LORQv3) and OHIP-14 questionnaire. Secondary objectives were to identify issues specific to oral rehabilitation, patients compliance to prosthetic rehabilitation, the effect of radiation treatment on prosthetic rehabilitation, to achieve meaningful differences over a time before & after prosthetic intervention, to carryout and document specific patient-deprived problem. Seventy-five oral cancer patients were studied. Patients were asked to rate their experience of dental problems before fabrication of prosthesis and after 1 year using LORQv3 and OHIP-14. The responses were compared on Likert scale. Patients reported with extreme problems before rehabilitation. After 1 year of prosthetic rehabilitation, there was improvement noticed in all the domain of LORQv3 and OHIP-14. Complete compliance to the use of prosthetic appliances for 1 year study period was noted. In response to the question no. 40 (LORQv3), only 15 patients who belonged to the obturator group, brought to notice the problems which were not addressed in the LORQv3 questionnaire. The study showed that the oral cancer patients coped well and adapted to near normal oral status after prosthetic rehabilitation. This contributed to the improved overall health-related quality of life.


Single-molecule force spectroscopy reveals folding steps associated with hormone binding and activation of the glucocorticoid receptor.
The glucocorticoid receptor (GR) is a prominent nuclear receptor linked to a variety of diseases and an important drug target. Binding of hormone to its ligand binding domain (GR-LBD) is the key activation step to induce signaling. This process is tightly regulated by the molecular chaperones Hsp70 and Hsp90 in vivo. Despite its importance, little is known about GR-LBD folding, the ligand binding pathway, or the requirement for chaperone regulation. In this study, we have used single-molecule force spectroscopy by optical tweezers to unravel the dynamics of the complete pathway of folding and hormone binding of GR-LBD. We identified a "lid" structure whose opening and closing is tightly coupled to hormone binding. This lid is located at the N terminus without direct contacts to the hormone. Under mechanical load, apo-GR-LBD folds stably and readily without the need of chaperones with a folding free energy of [Formula: see text] The folding pathway is largely independent of the presence of hormone. Hormone binds only in the last step and lid closure adds an additional [Formula: see text] of free energy, drastically increasing the affinity. However, mechanical double-jump experiments reveal that, at zero force, GR-LBD folding is severely hampered by misfolding, slowing it to less than 1·s-1 From the force dependence of the folding rates, we conclude that the misfolding occurs late in the folding pathway. These features are important cornerstones for understanding GR activation and its tight regulation by chaperones.


Td92, an outer membrane protein of Treponema denticola, induces osteoclastogenesis via prostaglandin E(2)-mediated RANKL/osteoprotegerin regulation.
Periodontitis is a chronic inflammatory disease of the periodontium that causes significant alveolar bone loss. Osteoclasts are bone-resorbing multinucleated cells. Osteoblasts regulate osteoclast differentiation by expression of RANKL and osteoprotegerin (OPG). Td92 is a surface-exposed outer membrane protein of Treponema denticola, a periodontopathogen. Although it has been demonstrated that Td92 acts as a stimulator of various proinflammatory mediators, the role of Td92 in alveolar bone resorption remains unclear. Therefore, in this study, we investigated the role of Td92 in bone resorption. Mouse bone marrow cells were co-cultured with calvariae-derived osteoblasts in the presence or absence of Td92. Osteoclast formation was assessed by TRAP staining. Expressions of RANKL, osteoprotegerin (OPG) and prostaglandin E(2) (PGE(2) ) in osteoblasts were estimated by ELISA. Td92 induced osteoclast formation in the co-cultures. In the osteoblasts, RANKL and PGE(2) expressions were up-regulated, whereas OPG expression was down-regulated by Td92. The addition of OPG inhibited Td92-induced osteoclast formation. The prostaglandin synthesis inhibitors NS398 and indomethacin were also shown to inhibit Td92-induced osteoclast formation. The effects of Td92 on the expressions of RANKL, OPG and PGE(2) in osteoblasts were blocked by NS398 or indomethacin. These results suggest that Td92 promotes osteoclast formation through the regulation of RANKL and OPG production via a PGE(2) -dependent mechanism.


Uterine rupture secondary to placenta percreta in a near-term pregnant woman with a history of hysterotomy.
Uterine rupture during near-term pregnancy is a life-threatening condition. A 31-year-old pregnant woman with a breech presentation at the gestation age of 35(+2) weeks had complained of a dull abdominal pain for days. She was treated 2 years ago with bilateral uterine artery ligation and hysterotomy for removal of the retained placenta. An aggravation of abdominal pain occurred suddenly 4 h after hospitalization. The cardiotocogram showed a fetal heart beat with loss of variability, but increasing deceleration. An urgent cesarean section was performed because of suspected placenta abruption. After successful delivery of the fetus, a protruding placental tissue was found on the fundal uterine wall. We performed wedge resection of the ruptured uterine wall with the aid of an intrauterine muscle injection of 20 IU oxytocin, a local injection of diluted vasopressin (1:60) into the myometrium around and into the rupture site, an intramuscular injection of 0.2 mg methylergonovine, and primary repair of the defect, but in vain. Cesarean hysterectomy was used to control the intractable bleeding. The accumulated blood loss was more than 10,000 mL. The final pathology confirmed placenta percreta with uterine rupture. Luckily, both mother and fetus recovered well and were discharged 7 days later. We concluded that women with retained placenta and/or postpartum hemorrhage managed by previous hysterotomy and uterine artery ligation still need careful prenatal care, since the possibility of re-occurrence of the placenta percreta is easily overlooked and may result in a further life-threatening situation, such as the uterine rupture in this case.


The effect of acid primer or conventional acid etching on microleakage in a photoactivated sealant.
The purpose of this study was to examine differences in microleakage in extracted human teeth when placing sealants using conventional acid etching or an acidic primer resin. Three experimental groupings were used: group 1--conventional acid etching with placement of light-cured sealant; group 2--application of acidic primer resin (Prompt-L-Pop) and light curing, followed by sealant placement; group 3--similar to group 2, but acidic primer and sealant were photocured after placement of sealant. Teeth were thermocycled, stained, sectioned and examined for marginal microleakage. In group 1, 94% of the enamel-sealant interfaces were free of microleakage. For groups 2 and 3, only 28% showed no leakage, with most leakage occurring at both margin and base areas. Nonparametric data analysis indicated acid etching demonstrated significantly lower microleakage than either treatment using the acidic primer resin (P<.001) and that leakage scores in the acidic primer groups were identical (P=.4011). Use of this specific acidic resin primer in lieu of conventional acid etching (whether cured prior to or subsequent to sealant placement) demonstrated greater incidence of microleakage and would not be advocated over traditional etching procedures.


Effect of ascorbic acid on endothelial dysfunction of epicardial coronary arteries in chronic smokers assessed by cold pressor testing.
In chronic smokers there is evidence for increased formation of oxygen-derived free radicals within the vessel wall impairing endothelial function. It has been suggested that the inactivation of endothelium-derived nitric oxide by oxygen free radicals contributes to endothelial dysfunction. Hence, we tested the hypothesis that in chronic smokers the antioxidant ascorbic acid could improve abnormal endothelial function of epicardial coronary arteries. Thirty-one patients (mean age 57 +/- 9 years) referred for routine diagnostic catheterization for evaluation of chest pain and without angiographically significant coronary artery stenoses were randomly assigned to one of the study groups to assess vasomotor response of epicardial coronary arteries due to cold pressor testing (CPT) before and after intravenous infusion of 3 g of ascorbic acid or 100 ml x 0.9% saline infusion. In 6 controls (mean age 55 +/- 3 years) CPT led to a similar increase in luminal area before and after ascorbic acid administration (26.5 +/- 15.0 vs. 28.4 +/- 17.7%, p = NS). In 15 chronic smokers (mean age 55 +/- 9 years), CPT induced a decrease in the luminal area of -18.5 +/- 6.3%. This flow-dependent vasoconstriction was significantly reversed to 7.7 +/- 6.2% (p < or = 0.03) vasodilation after intravenous ascorbic acid administration. In 10 chronic smokers (mean age 57 +/- 11 years) saline infusion (placebo) did not have a significant effect on CPT-induced vasoconstriction (-12.7 +/- 5.1 vs. -13.1 +/- 5.1%, p = NS). The CPT-induced increase in luminal area in chronic smokers after ascorbic acid infusion was significant compared to controls and placebo (each p < or = 0.05). Our assessment of endothelium-independent responses to nitroglycerin revealed no significant differences between the single study groups (p = NS). In chronic smokers acute intravenous administration of ascorbic acid significantly improves CPT-induced coronary endothelium-dependent dysfunction. According to the current understanding, this effect is due to improved cellular redox imbalance and prevention of nitric oxide inactivation in the endothelium and subendothelial space.


Modulatory effects of TGF-β1 and BMP6 on thecal angiogenesis and steroidogenesis in the bovine ovary.
Angiogenesis plays an integral role in follicular and luteal development and is positively regulated by several intra-ovarian factors including vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 2 (FGF2). Various transforming growth factor-β (TGF-β) superfamily members function as intra-ovarian regulators of follicle and luteal function, but their potential roles in modulating ovarian angiogenesis have received little attention. In this study, we used a bovine theca interna culture model (exhibiting characteristics of luteinization) to examine the effects of TGF-β1 and bone morphogenetic protein 6 (BMP6) on angiogenesis and steroidogenesis. VEGFA/FGF2 treatment promoted endothelial cell network formation but had little or no effect on progesterone and androstenedione secretion or expression of key steroidogenesis-related genes. TGF-β1 suppressed basal and VEGFA/FGF2-induced endothelial cell network formation and progesterone secretion, effects that were reversed by an activin receptor-like kinase 5 (ALK5) inhibitor (SB-431542). The ALK5 inhibitor alone raised androstenedione secretion and expression of several transcripts including CYP17A1. BMP6 also suppressed endothelial cell network formation under VEGFA/FGF2-stimulated conditions and inhibited progesterone secretion and expression of several steroidogenesis-related genes under basal and VEGFA/FGF2-stimulated conditions. These effects were reversed by an ALK1/2 inhibitor (K02288). Moreover, the ALK1/2 inhibitor alone augmented endothelial network formation, progesterone secretion, androstenedione secretion and expression of several steroidogenesis-related genes. The results indicate dual suppressive actions of both TGF-β1 and BMP6 on follicular angiogenesis and steroidogenesis. Further experiments are needed to unravel the complex interactions between TGF-β superfamily signalling and other regulatory factors controlling ovarian angiogenesis and steroidogenesis.


Analysis of sensitive questions across cultures: an application of multigroup item randomized response theory to sexual attitudes and behavior.
Answers to sensitive questions are prone to social desirability bias. If not properly addressed, the validity of the research can be suspect. This article presents multigroup item randomized response theory (MIRRT) to measure self-reported sensitive topics across cultures. The method was specifically developed to reduce social desirability bias by making an a priori change in the design of the survey. The change involves the use of a randomization device (e.g., a die) that preserves participants' privacy at the item level. In cases where multiple items measure a higher level theoretical construct, the researcher could still make inferences at the individual level. The method can correct for under- and overreporting, even if both occur in a sample of individuals or across nations. We present and illustrate MIRRT in a nontechnical manner, provide WinBugs software code so that researchers can directly implement it, and present 2 cross-national studies in which it was applied. The first study compared nonstudent samples from 2 countries (total n = 927) on permissive sexual attitudes and risky sexual behavior and related these to individual-level characteristics such as the Big Five personality traits. The second study compared nonstudent samples from 17 countries (total n = 6,195) on risky sexual behavior and related these to individual-level characteristics, such as gender and age, and to country-level characteristics, such as sex ratio.


Family and peer issues among adolescents with spina bifida and cerebral palsy.
Increasingly, children with disabling conditions are surviving through childhood into adolescence and beyond. This places increased importance on understanding adolescent, family, and peer relationships, which are critical to healthy development among adolescents in general and to transitions to successful adulthood among youths with physical disabilities in particular. The purpose of this study was to identify the patterns of family and peer interactions. One hundred two youths with spina bifida and 60 adolescents with cerebral palsy between the ages of 12 and 22 completed written psychological measures as well as an in-depth structured interview. Approximately 90% of youths with spina bifida and cerebral palsy resided at home, of whom 80.4% and 72% lived with both parents. Almost without exception, parental relationships were defined as positive, with no difference of attitude noted toward the mother and father. Relationships with parents for teenagers with spina bifida were marked by high levels of dependence on parents for personal care such as bowel programs and, for both groups, low levels of responsibility at home and lack of discussion with parents about sexuality or menstruation. Although friends were viewed as very important by most respondents (approximately 83%), relationships were characterized by extremely limited out-of-school contacts, negligible participation with organized social activities, and a primary orientation toward sedentary activities. Finally, regarding heterosexual relationships, whereas 44.1% of respondents with spina bifida and 54.2% of respondents with cerebral palsy said their friends dated, only 14.7% and 28.3% of study participants indicated that they had ever been on a date and, even for those teenagers, heterosexual social contacts were infrequent.(ABSTRACT TRUNCATED AT 250 WORDS)


Photobiomodulation in human muscle tissue: an advantage in sports performance?
Photobiomodulation (PBM) describes the use of red or near-infrared (NIR) light to stimulate, heal, and regenerate damaged tissue. Both preconditioning (light delivered to muscles before exercise) and PBM applied after exercise can increase sports performance in athletes. This review covers the effects of PBM on human muscle tissue in clinical trials in volunteers related to sports performance and in athletes. The parameters used were categorized into those with positive effects or no effects on muscle performance and recovery. Randomized controlled trials and case-control studies in both healthy trained and untrained participants, and elite athletes were retrieved from MEDLINE up to 2016. Performance metrics included fatigue, number of repetitions, torque, hypertrophy; measures of muscle damage and recovery such as creatine kinase and delayed onset muscle soreness. Searches retrieved 533 studies, of which 46 were included in the review (n = 1045 participants). Studies used single laser probes, cluster of laser diodes, LED clusters, mixed clusters (lasers and LEDs), and flexible LED arrays. Both red, NIR, and red/NIR mixtures were used. PBM can increase muscle mass gained after training, and decrease inflammation and oxidative stress in muscle biopsies. We raise the question of whether PBM should be permitted in athletic competition by international regulatory authorities.


The reflective component of the Mellow Bumps parenting intervention: Implementation, engagement and mechanisms of change.
Understanding why parenting programmes work or do not work, and for whom, is crucial for development of more effective parenting interventions. In this paper we focus on a specific component of Mellow Bumps: reflection on one's own childhood/past/life. We explore how this component was implemented, how participants engaged with it, the facilitating and constraining factors shaping this, whether and how it appeared to work, or not, and for whom. The paper analyses data from the Process Evaluation of the Trial of Healthy Relationships Initiatives for the Very Early years, which is evaluating two antenatal interventions delivered to vulnerable women, one of which is Mellow Bumps. Data were collected from January 2014 to June 2018 for 28 groups, 108 participants and 24 facilitators in a comprehensive and rigorous Process Evaluation designed to complement the Outcome Evaluation. Data were gathered at various time points using multiple methods, and were synthesised to triangulate findings. The reflective component was implemented with fidelity and participants engaged with it to varying degrees, dependent largely on the coherence of the group. Patchy attendance compromised the coherence of some groups, with the development of rapport, which is key to delivering reflective exercises, more difficult when group composition varied from week to week. Where there was a coherent group, powerful mechanisms of change, leading to stress reduction, included: relief through unburdening, empowerment through support given and received, reduced isolation through sharing anxieties, and control through self-care advice. A minority of highly vulnerable mothers seemed not to benefit from the reflective exercises and were marginalised within their groups. In order to minimise potential harmful effects of such exercises, allocation of participants to groups should strive to maximise group homogeneity. More research is needed to explore how very vulnerable parents can be supported in attending parenting interventions from start to finish.


Defoliation responses of western wheatgrass populations with diverse histories of prairie dog grazing.
Photosynthesis and regrowth were compared over a 10-day period following defoliation of about 75% of the tillers of western wheatgrass (Agropyron smithii) plants collected from a black-tailed prairie dog (Cynomys ludovicianus) town and a grazing exclosure at Wind Cave National Park, South Dakota. Prior to defoliation, dog town plants had more tillers, but fewer leaves per tiller, shorter and narrower leaf blades, more horizontal leaves, and higher leaf blade/leaf sheath ratios than plants from the grazing exclosure. Rates of net photosynthesis (PN) did not differ significantly among plants of the two populations, either prior to or following defoliation. From Days 2-10 following defoliation, PN of remaining undamaged leaves averaged 104% of predefoliation rates while PN of similar leaves on non-defoliated plants declined steadily with time. averaging only 79% predefoliation rates during this period. Following defoliation, transpiration rates followed similar trends to CO2 exchange, and rates did not differ between plants of the two populations. Absolute rates of leaf elongation and shoot production were greater in plants from the exclosure. However, defoliation of plants from the exclosure population resulted in a 20% reduction in their cumulative shoot dry weight, while cumulative shoot dry weight of plants from the prairie dog town was not significantly affected by defoliation. This apparent ability of plants from the prairie dog town population to withstand defoliation better than plants from the exclosure was atributed to factors such as the higher leaf blade/leaf sheath ratio and more horizontal leaf angles of plants from the former population.


NOTCH mutations: multiple faces in human malignancies.
NOTCH proteins have been implicated in multiple cellular functions, such as stem cell maintenance and cell fate determination. Initially identified as proto-oncogenes because they promote the development of certain types of leukemia, inactivating mutations of NOTCH were later reported. Together with the potential distinct functions of NOTCH family members, their ligands and associated niches, the precise roles of NOTCH in human cancers, particularly solid tumors, remain unsettled. In oral squamous cell carcinoma (OSCC), mutations of NOTCH1 are found in 10% to 15% tumors from Caucasian patients, mostly inactivating mutations. Recent studies of OSCC from Chinese patients, however, showed mutation rates of NOTCH1 about 50% with a considerable portion of potential activating mutations. These findings add another twist into the already complex picture of NOTCH alterations in human cancers, calling for further investigation to uncover what role exactly these molecules play in cancer initiation and progression to develop strategies targeting NOTCH signaling for cancer prevention and treatment.


HotSprint: database of computational hot spots in protein interfaces.
We present a new database of computational hot spots in protein interfaces: HotSprint. Hot spots are residues comprising only a small fraction of interfaces yet accounting for the majority of the binding energy. HotSprint contains data for 35 776 protein interfaces among 49 512 protein interfaces extracted from the multi-chain structures in Protein Data Bank (PDB) as of February 2006. The conserved residues in interfaces with certain buried accessible solvent area (ASA) and complex ASA thresholds are flagged as computational hot spots. The predicted hot spots are observed to correlate with the experimental hot spots with an accuracy of 76%. Several machine-learning methods (SVM, Decision Trees and Decision Lists) are also applied to predict hot spots, results reveal that our empirical approach performs better than the others. A web interface for the HotSprint database allows users to browse and query the hot spots in protein interfaces. HotSprint is available at http://prism.ccbb.ku.edu.tr/hotsprint; and it provides information for interface residues that are functionally and structurally important as well as the evolutionary history and solvent accessibility of residues in interfaces.


Microbial Communities in a Flow-Through Fish Farm for Lumpfish (Cyclopterus lumpus L.) During Healthy Rearing Conditions.
Lumpfish can efficiently remove sea lice from Atlantic salmon in net-pens, and production of lumpfish in closed fish farms is a new, fast developing industry in Norway. However, periodic outbreaks of bacterial diseases in the fish farms represent a large problem, both economically and ethically. Therefore it is important to obtain a better understanding of how microbial communities develop in these production facilities. Knowledge on the characteristics of microbial communities associated with healthy fish could also enable detection of changes associated with disease outbreaks at an early stage. In this study we have monitored microbial communities in a fish farm for lumpfish during normal operational conditions with no disease outbreak by using 16S rRNA gene amplicon sequencing. The study involved weekly samplings of water and biofilms from fish tanks, and fish. The results revealed that the microbial communities in fish tank water were different from the intake water. The water and biofilm in fish tanks were highly similar in regards to microbial community members, but with large differences in relative abundances for some taxa. The sampled fish were associated with mostly the same taxa as in tank water and biofilm, but more variation in relative abundances of different taxonomic groups occurred. The microbial communities in the fish farm seemed stable over time, and were dominated by marine bacteria and archaea within Alphaproteobacteria, Epsilonproteobacteria, Flavobacteria, Gammaproteobacteria, Thaumarchaeota, Planctomycetes, Sphingobacteriia, and Verrucomicrobiae (>10% relative abundance). Bacterial genera known to include fish-pathogenic strains were detected in all types of sample materials, but with low relative abundances (<5%). Exceptions were some samples of fish, biofilm and water with high relative abundance of Tenacibaculum (<85.8%) and Moritella (<82%). In addition, some of the eggs had a high relative abundance of Tenacibaculum (<89.5%). Overall, this study shows that a stable microbial community dominated by various genera of non-pathogenic bacteria is associated with a healthy environment for rearing lumpfish. Taxa with pathogenic members were also part of the microbial communities during healthy conditions, but the stable non-pathogenic bacteria may limit their growth and thereby prevent disease outbreaks.


Effects of a high-fiber, low-fat diet intervention on serum concentrations of reproductive steroid hormones in women with a history of breast cancer.
Diet intervention trials are testing whether postdiagnosis dietary modification can influence breast cancer recurrence and survival. One possible mechanism is an effect on reproductive steroid hormones. Serum reproductive steroid hormones were measured at enrollment and 1 year in 291 women with a history of breast cancer who were enrolled onto a randomized, controlled diet intervention trial. Dietary goals for the intervention group were increased fiber, vegetable, and fruit intakes and reduced fat intake. Estradiol, bioavailable estradiol, estrone, estrone sulfate, androstenedione, testosterone, dehydroepiandrosterone sulfate, follicle-stimulating hormone, and sex hormone-binding globulin were measured. The intervention (but not the comparison) group reported a significantly lower intake of energy from fat (21% v 28%), and higher intake of fiber (29 g/d v 22 g/d), at 1-year follow-up (P <.001). Significant weight loss did not occur in either group. A significant difference in the change in bioavailable estradiol concentration from baseline to 1 year in the intervention (-13 pmol/L) versus the comparison (+3 pmol/L) group was observed (P <.05). Change in fiber (but not fat) intake was significantly and independently related to change in serum bioavailable estradiol (P <.01) and total estradiol (P <.05) concentrations. Results from this study indicate that a high-fiber, low-fat diet intervention is associated with reduced serum bioavailable estradiol concentration in women diagnosed with breast cancer, the majority of whom did not exhibit weight loss. Increased fiber intake was independently related to the reduction in serum estradiol concentration.


Shufeng Jiedu Capsule protect against acute lung injury by suppressing the MAPK/NF-κB pathway.
This study sought to investigate the protective effect of an alternative medicine, Shufeng Jiedu Capsule, in acute lung injury and inflammation signaling pathways related to that action. Hematoxylin and eosin (HE) staining was used to observe pathological changes in rat lung tissue, arterial blood was subjected to blood gas analysis and lactic acid levels were determined, immunofluorescent staining for interleukin-1β (IL-1β) was performed, enzyme linked immunosorbent assay (ELISA) was used to detect biomarkers of the nuclear factor-κB (NF-κB) inflammation pathway including IL-1β and tumor necrosis factor α (TNF-α), biomarkers of the mitogen-activated protein kinase (MAPK) signal pathway including P-selectin, transforming growth factor β (TGF-β), keratinocyte-derived chemokine (KC), and C-Jun/AP-1 were measured, and real-time PCR was used to detect NF-κB mRNA. Results in rats with lipopolysaccharide-induced acute lung injury suggested that Shufeng Jiedu Capsule may increase the partial pressure of oxygen in lung tissue, decrease lactic acid levels, inhibit inflammatory factors such as IL-1β and TNF-α, and suppress the levels of P-selectin, TGF-β, KC, C-Jun/AP-1, and NF-κB mRNA. Thus, Shufeng Jiedu Capsule is a traditional medicine that may alleviate acute lung injury by suppressing the MAPK/NF-κB signaling pathway.


In Vitro Antimicrobial Activity of Spices and Medicinal Herbs against Selected Microbes Associated with Juices.
In the present investigation, comparison of antimicrobial activities of different spices, Curcuma longa, Zingiber officinale, and Mentha arvensis, and medicinal herbs, such as Withania somnifera, Rauvolfia serpentina, Emblica officinalis, Terminalia arjuna, and Centella asiatica, was evaluated. Different extraction solvents (acetone, methanol, ethanol, and water) were used and extracts were examined against Bacillus cereus, Serratia sp., Rhodotorula mucilaginosa, Aspergillus flavus, and Penicillium citrinum isolated from juices. Extracts from the medicinal herb and spices have significant activity. B. cereus was the most sensitive and R. mucilaginosa was the most resistant among the microorganisms tested. Ethanolic and methanolic extract of C. asiatica displayed maximum diameter of inhibition zone against bacteria and yeast and percentage mycelial inhibition against moulds. This study confirmed the potential of selected extracts of spices as effective natural food preservative in juices.


Mortality of rapid response team patients in Australia: a multicentre study.
Most studies of the rapid response team (RRT) investigate the effect of introducing an RRT on outcomes of all hospitalised patients. Less information exists on RRT patient epidemiology, or changes in RRT call numbers with time. To estimate the inhospital mortality of patients subject to RRT review, the proportion of inhospital deaths reviewed by the RRT, and changes in annual RRT call numbers with time. Retrospective observational study in adult RRT equipped Australian hospitals for up to 10 years (2000-2009). Thirty-four per cent (35/102) of the Australian adult RRT-equipped hospitals provided annual hospital admissions and deaths, intensive care unit admissions and RRT calls. They also provided the number of patients reviewed by the RRT and the number of inhospital deaths in such patients. Over the study period, there were 4.91 million hospital admissions, 196 488 ICU admissions and 99 377 RRT calls. Most data arose from Victoria, New South Wales and Western Australia, and from public tertiary hospitals. Among the 27 hospitals contributing at least 4 years of data, annual RRT calls per 1000 admissions was higher in the last year compared with the first year of data submission in 23 hospitals (range of increase, 11.9%- 777.4%; median, 90%; interquartile range, 40%-180%). In the remaining four hospitals, annual RRT calls per 1000 admissions were lower in the last year compared with the first year (range of decrease, - 5.5% to - 29.8%). Among the 70 924 RRT patients for whom the outcome was known, there were 17 260 deaths (24.3%). We calculate that the RRT reviewed 17 260 of 79 476 patients (21.7%) who died in hospital over the study period. In the 2008-09 financial year, there were 18 800 RRT calls for at least 14 743 patients. Annual RRT calls are increasing in many Australian hospitals, and now affect more than 14 700 patients annually. Inhospital mortality of RRT patients is about 25%, and about 20% of patients who die in hospital are reviewed by the RRT. Further research is needed to understand the reason for the high inhospital mortality of RRT patients.


Functional neuroimaging and psychology: what have you done for me lately?
Functional imaging has become a primary tool in the study of human psychology but is not without its detractors. Although cognitive neuroscientists have made great strides in understanding the neural instantiation of countless cognitive processes, commentators have sometimes argued that functional imaging provides little or no utility for psychologists. And indeed, myriad studies over the last quarter century have employed the technique of brain mapping-identifying the neural correlates of various psychological phenomena-in ways that bear minimally on psychological theory. How can brain mapping be made more relevant to behavioral scientists broadly? Here, we describe three trends that increase precisely this relevance: (i) the use of neuroimaging data to adjudicate between competing psychological theories through forward inference, (ii) isolating neural markers of information processing steps to better understand complex tasks and psychological phenomena through probabilistic reverse inference, and (iii) using brain activity to predict subsequent behavior. Critically, these new approaches build on the extensive tradition of brain mapping, suggesting that efforts in this area-although not initially maximally relevant to psychology-can indeed be used in ways that constrain and advance psychological theory.


A novel component of the Rhodobacter sphaeroides Fla1 flagellum is essential for motor rotation.
Here we describe a novel component essential for flagellar rotation in Rhodobacter sphaeroides. This protein is encoded by motF (RSP_0067), the first gene of a predicted transcriptional unit which contains two hypothetical genes. Sequence analysis indicated that MotF is a bitopic membrane-spanning protein. Protease sensitivity assays and green fluorescent protein (GFP) fusions confirmed this prediction and allowed us to conclude that the C terminus of MotF is located in the periplasmic space. Wild-type cells expressing a functional GFP-MotF fusion show a single fluorescent focus per cell. The localization of this protein in different genetic backgrounds allowed us to determine that normal localization of MotF depends on the presence of FliL and MotB. Characterization of a ΔmotF pseudorevertant strain revealed that a single nucleotide change in motB suppresses the Mot(-) phenotype of the motF mutant. Additionally, we show that MotF also becomes dispensable when other mutant alleles of motB previously isolated as second-site suppressors of ΔfliL were expressed in the motF mutant strain. These results show that MotF is a new component of the Fla1 flagellum, which together with FliL is required to promote flagellar rotation, possibly through MotB.


Tracing the conversion process from primordial germ cells to pluripotent stem cells in mice.
To understand mechanisms underlying acquisition of pluripotency, it is critical to identify cells that can be converted to pluripotent stem cells. For this purpose, we focused on unipotent primordial germ cells (PGCs), which can be reprogrammed into pluripotent embryonic germ (EG) cells under defined conditions. Treatment of PGCs with combinations of signaling inhibitors, including inhibitors of MAP2K (MEK), GSK3B (GSK-3beta), and TGFB (TGFbeta) type 1 receptors, induced cells to enter a pluripotent state at a high frequency (12.1%) by Day 10 of culture. When we employed fluorescence-activated cell sorting to monitor conversion of candidate cells to a pluripotent state, we observed a cell cycle shift to S phase, indicating enrichment of pluripotent cells, during the early phase of EG formation. Transcriptome analysis revealed that PGCs retained expression of some pluripotent stem cell-associated genes, such as Pou5f1 and Sox2, during EG cell formation. On the other hand, PGCs lost their germ lineage characteristics and acquired expression of pluripotent stem cell markers, such as Klf4 and Eras. The overall gene expression profiles revealed by this system provide novel insight into how pluripotency is acquired in germ-committed cells.


WAAR (World Alliance against Antibiotic Resistance): Safeguarding antibiotics.
Resistance to antibiotics has increased recently to a dramatic extend, and the pipeline of new antibiotics is almost dry for the five next years. Failures happen already for trivial community acquired infections, like pyelonephritis, or peritonitis, and this is likely to increase. Difficult surgical procedures, transplants, and other immunosuppressive therapies will become far more risky. Resistance is mainly due to an excessive usage of antibiotics, in all sectors, including the animal one. Action is urgently needed. Therefore, an alliance against MDRO has been recently created, which includes health care professionals, consumers, health managers, and politicians. The document highlights the different proposed measures, and represents a strong consensus between the different professionals, including general practicionners, and veterinarians.


Biaryl phosphane ligands in palladium-catalyzed amination.
Palladium-catalyzed amination reactions of aryl halides have undergone rapid development in the last 12 years, largely driven by the implementation of new classes of ligands. Biaryl phosphanes have proven to provide especially active catalysts in this context. This Review discusses the application of these catalysts in C-N cross-coupling reactions in the synthesis of heterocycles and pharmaceuticals, in materials science, and in natural product synthesis.


Minimally Invasive Approach for Resection of Parameningeal Rhabdomyosarcoma.
Background About one-third of rhabdomyosarcomas arise in the head and neck, with parameningeal primaries accounting for half of these. Principles of management involve chemotherapy, radiation, or both, in addition to surgical biopsy, debulking, and complete or near-complete resection. In the head and neck, diagnostic biopsies have historically been performed without attempt at resection due to proximity to critical structures and cosmetic considerations. Methods Retrospective chart review of three cases of rhabdomyosarcoma at the cranial base managed through minimally invasive endoscopic surgical resection and adjuvant therapy. Results Three patients were identified as having undergone endoscopic surgical debulking or margin-negative resection of a rhabdomyosarcoma of the cranial base. Two of three patients had complete resection based on intraoperative margin control. All three patients underwent adjuvant therapy within 1 month of diagnosis. Follow-up time ranged from 5 months to 3 years with all patients disease-free at last follow-up. Conclusion Skull base surgeons should routinely be involved in multidisciplinary treatment planning for parameningeal rhabdomyosarcomas, as surgical options have evolved to allow for potential endoscopic resection with low morbidity and no or minimal delay in additional treatment options.


Effectiveness and cost effectiveness of thrombolysis in patients with acute pulmonary embolism.
Acute pulmonary embolism is a common, life-threatening, cardiopulmonary disorder with a high mortality rate within the first 3 months of diagnosis. As prompt anticoagulation is the mainstay of therapy in patients with pulmonary embolism, the clinical utility and cost effectiveness of systemic thrombolysis is debated. Pulmonary embolism with cardiogenic shock and hypotension is characterized as 'massive' in nature and an accepted indication for thrombolysis, although catheter-directed embolectomy with or without local lytic therapy is preferred in centers with appropriate experience. Acute right ventricular dysfunction is a poor prognostic indicator in patients with pulmonary embolism. The most recent randomized controlled trial of systemic thrombolysis in patients with submassive pulmonary embolism and right ventricular dysfunction found that, compared with heparin alone, alteplase and heparin reduced the risk of clinical deterioration requiring treatment escalation, but did not reduce the risk of death. Subsequently, a formal cost effectiveness concluded that alteplase and heparin was slightly less effective and marginally more expensive than heparin alone in this patient population. Current evidence does not support the use of thrombolytic agents in most hemodynamically stable patients with right ventricular dysfunction. However, improved methods of risk stratification may help to identify subgroups of patients at high risk of death that might benefit from systemic thrombolysis.


Use of colonoscopy as a primary screening test for colorectal cancer in average risk people.
The use of colonoscopy as a primary screening test for colorectal cancer (CRC) in average risk adults is a subject of controversy. Our primary objective was to build a predictive model based on a few simple variables that could be used as a guide for identifying average risk adults more suitable for examination with colonoscopy as a primary screening test. The prevalence of advanced adenomas was assessed by primary screening colonoscopy in 2210 consecutive adults at least 40 yr old, without known risk factors for CRC. Age, gender, and clinical and biochemical data were compared among people without adenomas, those with non-advanced adenomas, and those with any advanced neoplasm. A combined score to assess the risk of advanced adenomas was built with the variables selected by multiple logistic regression analysis. Neoplastic lesions were found in 617 subjects (27.9%), including 259 with at least one neoplasm that was 10 mm or larger, villous, or with moderate-to-severe dysplasia, and 11 with invasive cancers. Advanced lesions were more frequent among men, older people, and those with a higher body mass index (BMI). These three variables were independent predictors of advanced adenomas in multivariate analysis. A score combining age, sex, and BMI was developed as a guide for identifying individuals more suitable for screening colonoscopy. Age, gender, and BMI can be used to build a simple score to select those average risk adults who might be candidates for primary screening colonoscopy.


Clinical trials in irritable bowel syndrome: a review.
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders and it is characterized by episodes of abdominal pain and altered bowel functions. The specific bowel disturbances of diarrhea, constipation or an alternation between the two defines the IBS subtypes of diarrhea-predominant, constipation-predominant, and mixed or alternating IBS. Because of the abnormalities in bowel states associated with each IBS subtype, it is not likely that one agent would successfully treat all three subtypes. As a result, clinical trials have focused, for the most part, on one IBS subtype. Over the past 2 decades very few agents have achieved regulatory approval for the treatment of IBS. In the present article we review publications reporting on phase 2 and phase 3 studies evaluating agents to potentially be used in the treatment of patients with IBS.


Phytol and its metabolites phytanic and pristanic acids for risk of cancer: current evidence and future directions.
This review summarizes the current evidence on the potential role of phytol, a microbial metabolite of chlorophyl A, and its metabolites, phytanic and pristanic acids, in carcinogenesis. Primary food sources in Western diets are the nut skin for phytol and lipids in dairy, beef and fish for its metabolites. Phytol and its metabolites gained interest as dietary compounds for cancer prevention because, as natural ligands of peroxisome proliferator-activated receptor-α and -γ and retinoid X receptor, phytol and its metabolites have provided some evidence in cell culture studies and limited evidence in animal models of anti-carcinogenic, anti-inflammatory and anti-metabolic-syndrome properties at physiological concentrations. However, there may be a narrow range of efficacy, because phytol and its metabolites at supra-physiological concentrations can cause in vitro cytotoxicity in non-cancer cells and can cause morbidity and mortality in animal models. In human studies, evidence for a role of phytol and its metabolites in cancer prevention is currently limited and inconclusive. In short, phytol and its metabolites are potential dietary compounds for cancer prevention, assuming the challenges in preventing cytotoxicity in non-cancer cells and animal models and understanding phytol metabolism can be mitigated.


Expression of protein S100A4 is a predictor of recurrence in colorectal cancer.
To investigate the prognostic significance of S100A4 expression in colorectal cancer and its correlation with expression of E-cadherin and p53. A cohort of archival formalin-fixed paraffin-embedded specimens was selected from 127 patients with colorectal cancer who underwent surgical resection between April 2000 and March 2004 at the Department of Surgery, Korea University Guro Hospital. The expression of protein S100A4 was evaluated according to the proportion of positively stained cancer cells. In each case, three core biopsies with a diameter of 2 mm were punched out and positioned in a recipient paraffin array block. Four-microm sections of these tissue array blocks were used for immunohistochemical analysis of protein S100A4, E-cadherin, and p53. Clinicopathological data were based on the original histopathologic reports and clinical records of patients. In normal colorectal mucosa, protein S100A4 immunoreactivity was clearly absent in both cytoplasm and nucleus. However, positive immunoreactivity of protein S100A4 was detected in 45 (35.4%) of the tumor cases. There was no significant association between positive immunoreactivity of protein S100A4 and clinicopathological parameters such as tumor differentiation or TNM stage, and also no correlation between the reactivity and E-cadherin or p53 expression. However, positive immunoreactivity of protein S100A4 was found to be associated with tumor recurrence (P = 0.004), and was also associated with significantly worse overall survival in the Kaplan-Meyer survival analysis (P = 0.044). After adjustment for tumor differentiation, tumor depth and nodal status, however, it failed to achieve statistical significance (P = 0.067). The expression of protein S100A4 is associated with tumor recurrence and poor overall survival in patients with colorectal cancer.


Plasmidome-analysis of ESBL-producing escherichia coli using conventional typing and high-throughput sequencing.
Infections caused by Extended spectrum β-lactamase (ESBL)-producing E. coli are an emerging global problem, threatening the effectiveness of the extensively used β-lactam antibiotics. ESBL dissemination is facilitated by plasmids, transposons, and other mobile elements. We have characterized the plasmid content of ESBL-producing E. coli from human urinary tract infections. Ten diverse isolates were selected; they had unrelated pulsed-field gel electrophoresis (PFGE) types (<90% similarity), were from geographically dispersed locations and had diverging antibiotic resistance profiles. Three isolates belonged to the globally disseminated sequence type ST131. ESBL-genes of the CTX-M-1 and CTX-M-9 phylogroups were identified in all ten isolates. The plasmid content (plasmidome) of each strain was analyzed using a combination of molecular methods and high-throughput sequencing. Hidden Markov Model-based analysis of unassembled sequencing reads was used to analyze the genetic diversity of the plasmid samples and to detect resistance genes. Each isolate contained between two and eight distinct plasmids, and at least 22 large plasmids were identified overall. The plasmids were variants of pUTI89, pKF3-70, pEK499, pKF3-140, pKF3-70, p1ESCUM, pEK204, pHK17a, p083CORR, R64, pLF82, pSFO157, and R721. In addition, small cryptic high copy-number plasmids were frequent, containing one to seven open reading frames per plasmid. Three clustered groups of such small cryptic plasmids could be distinguished based on sequence similarity. Extrachromosomal prophages were found in three isolates. Two of them resembled the E. coli P1 phage and one was previously unknown. The present study confirms plasmid multiplicity in multi-resistant E. coli. We conclude that high-throughput sequencing successfully provides information on the extrachromosomal gene content and can be used to generate a genetic fingerprint of possible use in epidemiology. This could be a valuable tool for tracing plasmids in outbreaks.


Association of Previous Smoking Habit and Perceived Social Discrimination with the Risk of Multi-Drug Resistant Tuberculosis in Central Nepal.
Multidrug-resistant tuberculosis (MDR TB) caused by Mycobacterium tuberculosis resistant to both Isoniazid and Rifampicin with or without resistant to other drug, is among the most alarming pandemic problem. The objectives of this study was to assess the risk factors of MDR TB in Central Nepal. A matched case control study was conducted among 186 cases of MDR TB and 372 non-MDR TB controls from central region of Nepal. Pretested questionnaires containing socio-economic, cultural & behavioral; environmental, biological and health service factors were used. Variables significant in bivariate analysis were entered in multiple regression models for further analysis. After adjusting for confounders, previous smoking habit (aOR= 4.5,(95%CI(1.24-16.2)) (p=0.04), and perceived social discrimination (aOR=5.83,95%CI (1.77-19.71)) (P=0.021) independently predicted greater MDR TB risk. Encouraging MDR TB cases for smoking cessation through awareness activities should be a priority. Stigma reduction programs should include the empowerment of patients and communities while promoting TBrelated research for further exploration into the risk factors of TB and associated stigma.


Dockomatic - automated ligand creation and docking.
The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user friendly Graphical User Interface (GUI) application that eases and automates the creation and management of AutoDock jobs for high throughput screening of ligand to receptor interactions. DockoMatic allows the user to invoke and manage AutoDock jobs on a single computer or cluster, including jobs for evaluating secondary ligand interactions. It also automates the process of collecting, summarizing, and viewing results. In addition, DockoMatic automates creation of peptide ligand .pdb files from strings of single-letter amino acid abbreviations. DockoMatic significantly reduces the complexity of managing multiple AutoDock jobs by facilitating ligand and AutoDock job creation and management.


From Bilski back to Benson: preemption, inventing around, and the case of genetic diagnostics.
The long-anticipated decision in Bilski v. Kappos was supposed to end uncertainty regarding the patentability of process claims (or, at the least, business method claims). Instead, the opinion featured a series of anomalies: The Court emphasized strict construction of the Patent Act, but acknowledged three judge-made exceptions to patentability. It disapproved State Street, the Federal Circuit case that had upheld business method patents, but could muster only four votes for the proposition that business methods are in fact unpatentable. But even though the Court upheld business method patents, it invalidated all of Bilski's hedging claims. And while the Justices agreed on one thing - a patent that "preempts" something (a mathematical formula, an approach, a commonly used idea, a wide swath of technological developments, the public's access) is bad - they failed to operationalize the concept. That problem had plagued the law prior to State Street; in the interest of preventing the same set of problems from recurring, this Article uses recent empirical studies on gene patents to tease out indicia ("clues") to supplement the machine-or-transformation test for determining when a claim is preemptive and therefore invalid. Chief among these clues is the inability to invent around claims that cover broad prospects.


HPV DNA testing improves CIN2+ risk stratification and detection of CIN2+ in delayed triage of ASCUS and LSIL. A population-based follow-up study from Western Norway.
In Norway, Pap smears with atypical squamous cells of uncertain significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are triaged after 6 months. The aim of the study was to evaluate effects of implementing human papillomavirus (HPV) test (2005) in delayed triage of ASCUS and LSIL in a cohort of women from Western Norway. After a survey of 119,469 cervical Pap smears during 2005-2007, a total of 1055 women with an index ASCUS or LSIL were included in the study and followed up for 3-6 years with respect to progression into cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Overall sensitivity for detection of CIN2+ with HPV testing and cytology was 96% and 72%, respectively. The sensitivity for detection of CIN2+ was not affected by age, but the specificity of the HPV test increased with age. Thus, for the age groups <34 years, 34-50 years, and >50 years, the specificity of a positive HPV test to detect CIN2+ was 47%, 71%, and 82%, respectively. Positive predictive values for CIN2+ in women with positive cytology, positive HPV test, negative cytology, negative HPV test, or negative HPV and cytology tests were 52%, 41%, 8%, 1.5%, and 0.4%, respectively. HPV testing resulted in a net 22% increased detection of CIN2+. Fifty-six percent of CIN2+ was detected at an earlier time point with HPV testing in triage. Implementation of HPV testing in delayed triage of ASCUS and LSIL improved the stratification of CIN2+ risk and increased CIN2+ detection and at an earlier time point than with triage by cytology alone.


Milk and acid-base balance: proposed hypothesis versus scientific evidence.
Recently the lay press has claimed a hypothetical association among dairy product consumption, generation of dietary acid, and harm to human health. This theoretical association is based on the idea that the protein and phosphate in milk and dairy products make them acid-producing foods, which cause our bodies to become acidified, promoting diseases of modern civilization. Some authors have suggested that dairy products are not helpful and perhaps detrimental to bone health because higher osteoporotic fracture incidence is observed in countries with higher dairy product consumption. However, scientific evidence does not support any of these claims. Milk and dairy products neither produce acid upon metabolism nor cause metabolic acidosis, and systemic pH is not influenced by diet. Observations of higher dairy product intake in countries with prevalent osteoporosis do not hold when urban environments are compared, likely due to physical labor in rural locations. Milk and other dairy products continue to be a good source of dietary protein and other nutrients. Key teaching points: Measurement of an acidic pH urine does not reflect metabolic acidosis or an adverse health condition. The modern diet, and dairy product consumption, does not make the body acidic. Alkaline diets alter urine pH but do not change systemic pH. Net acid excretion is not an important influence of calcium metabolism. Milk is not acid producing. Dietary phosphate does not have a negative impact on calcium metabolism, which is contrary to the acid-ash hypothesis.


Bone marrow niches for hematopoietic stem cells and immune cells.
In mammals, hematopoietic stem cells (HSCs), which give rise to all blood cells and their progenies, including immune cells are controlled by special microenvironments, termed niches in the bone marrow during homeostasis and infection. However, the identity, nature and function of these niches remain unclear. It has been reported that HSCs are in contact with osteoblasts lining the bone surface and osteoblasts act as niches for HSCs (termed endosteal niche). However, recent studies suggest that only a small number of HSCs reside in the endosteal niche. In contrast, many HSCs are shown to be in contact with endothelial cells in the marrow. In addition, recent studies suggest that primitive mesenchymal cells, including CXCL12-abundant reticular (CAR) cells and Nestin-expressing cells, which have the ability to differentiate into adipocytes as well as osteoblasts act as niches for HSCs. Here we review candidate niches for HSCs in the bone marrow controlling hematopoiesis and chronic inflammation.


Detecting and Quantifying Changing Selection Intensities from Time-Sampled Polymorphism Data.
During his well-known debate with Fisher regarding the phenotypic dataset of Panaxia dominula, Wright suggested fluctuating selection as a potential explanation for the observed change in allele frequencies. This model has since been invoked in a number of analyses, with the focus of discussion centering mainly on random or oscillatory fluctuations of selection intensities. Here, we present a novel method to consider nonrandom changes in selection intensities using Wright-Fisher approximate Bayesian (ABC)-based approaches, in order to detect and evaluate a change in selection strength from time-sampled data. This novel method jointly estimates the position of a change point as well as the strength of both corresponding selection coefficients (and dominance for diploid cases) from the allele trajectory. The simulation studies of this method reveal the combinations of parameter ranges and input values that optimize performance, thus indicating optimal experimental design strategies. We apply this approach to both the historical dataset of P. dominula in order to shed light on this historical debate, as well as to whole-genome time-serial data from influenza virus in order to identify sites with changing selection intensities in response to drug treatment.


Effect of honey on bacterial translocation and intestinal morphology in obstructive jaundice.
To evaluate the effects of honey on bacterial translocation and intestinal villus histopathology in experimental obstructive jaundice. Thirty Wistar-Albino rats were randomly divided into three groups each including 10 animals: group I, sham-operated; group II, ligation and section of the common bile duct (BDL); group III, bile duct ligation followed by oral supplementation of honey (BDL + honey) 10 g/kg per day. Liver, blood, spleen, mesenteric lymph nodes, and ileal samples were taken for microbiological, light and transmission electrone microscopic examination. Although the number of villi per centimeter and the height of the mucosa were higher in sham group, there was no statistically significant difference between sham and BDL + honey groups (P > 0.05). On the other hand, there was a statistically significant difference between BDL group and other groups (P < 0.05). The electron microscopic changes were also different between these groups. Sham and honey groups had similar incidence of bacterial translocation (P > 0.05). BDL group had significantly higher rates of bacterial translocation as compared with sham and honey groups. Bacterial translocation was predominantly detected in mesenteric lymph nodes. Supplementation of honey in presence of obstructive jaundice ameliorates bacterial translocation and improves ileal morphology.


Prostate Biopsy Features: A Comparison Between the Pre- and Post-2012 United States Preventive Services Task Force Prostate Cancer Screening Guidelines With Emphasis on African American and Septuagenarian Men.
We compare prostate biopsy (Pbx) characteristics from 3 years prior to the 2012 United States Preventive Services Task Force (USPSTF) prostate cancer (PCa) screening guidelines with those of 2018, with a focus on African American (AA) men and healthy men aged 70 to 80 years. We completed a retrospective comparative analysis of 1703 sequential patients that had had a Pbx from 2010 to 2012 (3 years) with 383 patients biopsied in 2018. Data was collected on patient age, race, prostate-specific antigen (PSA), digital rectal examination (DRE), total number of biopsies performed, and Gleason sum score (GSS). The data was analyzed to determine whether the 2012 USPSTF screening recommendations affected PCa characteristics. Two study groups were defined as group A and B, Pbx prior to the 2012 USPSTF screening guidelines and that of 2018, respectively. The study population consisted of 71% high-risk AA patients. In Group A (pre-2012 USPSTF guidelines), 567 patients/year underwent a Pbx versus Group B, 383 patients/year, a 32% reduction post-USPSTF. The annual positive Pbx rate for Group A is 134/year versus Group B with 175/year, a 31% increase post-USPSTF. In Group B, there was a 94% relative increase in total positive biopsies. Group A had high-grade PCa (GSS 7-10) in 51.5% versus 60.5% in Group B, a 9% increase post-USPSTF. The proportion of patients with a PSA 10 ng/mL or higher was 25.4% in group A versus 29.3% in group B. The age group of 70 to 80 years demonstrated an increasing trend for patients with PSA 10 ng/mL and higher, 31% in Group A versus 38% in Group B; high-grade tumors (GSS 7-10) occurred in 61% in Group A versus 65% in Group B. After the 2012 USPSTF guidelines against PCa screening, our study shows decreased prostate cancer screening with decreased Pbx, increased PCa diagnosis, and increased high-grade (GSS 7-10) PCa. These trends were especially notable in the 70- to 80-year age group, which showed a larger proportion of total patients (compared with pre-2012 USPSTF guidelines), increased PCa grades, increased PSA levels, and a higher percentage of patients with greater than 50% positive cores. As our patient population consists of 71% AA patients, our results support aggressive PCa screening for high-risk patients, which includes AA men, men with a family history of PCa, and healthy men aged 70 to 80 years.


Neutrophil defect associated with malignant infantile osteopetrosis.
We studied the phagocytes from three infants with malignant osteopetrosis and from their families in an attempt to define further the phagocyte abnormalities associated with this disorder. The rapid membrane potential depolarization in response to the soluble stimuli formylmethionylleucylphenylalanine (FMLP) and phorbol myristate acetate (PMA) served as a measure of neutrophil activation, with 3,3-dipentyloxacarbocyanine (diOC5 [3]) used as the probe. A fluorescence-activated cell sorter (FACS) allowed us to use small volumes of blood in a new quantitative evaluation of neutrophil response. The neutrophils from the infants with malignant osteopetrosis were very minimally activated with either stimulus, as demonstrated by incomplete membrane potential depolarization (10% to 15% of normal controls). This finding indicates that malignant osteopetrosis is accompanied by a significantly reduced neutrophil response to stimulation. The abnormal activation process was also reflected in the respiratory burst response of the patients' neutrophils and monocytes. Fifty percent to 60% of the infants' neutrophils totally failed to reduce nitro blue tetrazolium dye (NBT), 30% to 40% of the cells showed only slight reduction after PMA or FMLP stimulation, and only 5% to 10% demonstrated normal reduction. Peripheral blood monocytes failed to reduce NBT in 35% to 70% of the cells tested. Similar testing of granulocyte-macrophage colonies grown in vitro from circulating progenitor cells also showed an abnormal distribution of response to PMA, with a majority of colonies showing a decrease or absence of NBT reduction. Thus control of expression of the osteopetrotic defect occurs at or before the progenitor cell level.


Achromatic light patterning and improved image reconstruction for parallelized RESOLFT nanoscopy.
Fluorescence microscopy is rapidly turning into nanoscopy. Among the various nanoscopy methods, the STED/RESOLFT super-resolution family has recently been expanded to image even large fields of view within a few seconds. This advance relies on using light patterns featuring substantial arrays of intensity minima for discerning features by switching their fluorophores between 'on' and 'off' states of fluorescence. Here we show that splitting the light with a grating and recombining it in the focal plane of the objective lens renders arrays of minima with wavelength-independent periodicity. This colour-independent creation of periodic patterns facilitates coaligned on- and off-switching and readout with combinations chosen from a range of wavelengths. Applying up to three such periodic patterns on the switchable fluorescent proteins Dreiklang and rsCherryRev1.4, we demonstrate highly parallelized, multicolour RESOLFT nanoscopy in living cells for ~100 × 100 μm2 fields of view. Individual keratin filaments were rendered at a FWHM of ~60-80 nm, with effective resolution for the filaments of ~80-100 nm. We discuss the impact of novel image reconstruction algorithms featuring background elimination by spatial bandpass filtering, as well as strategies that incorporate complete image formation models.


Effectiveness of whole brain radiotherapy in the treatment of brain metastases: a systematic review.
Brain metastases are the most common intracranial tumour in adults, estimated to occur in up to 40% of patients with cancer. Despite being used in clinical practice for 50 years, the effectiveness of whole brain radiotherapy for the treatment of brain metastases remains uncertain. To assess the effectiveness of whole brain radiotherapy (WBRT) on survival and quality of life. To identify whether patient performance status, number of brain metastases, extent of extracranial disease and primary site of cancer are important effect modifiers. Systematic literature review. Electronic searches of four databases, augmented by hand searches of the most frequently encountered journal and assessment of the reference lists of consensus statements and all retrieved papers. Included papers underwent structured data extraction, assessment and qualitative synthesis. Thirty-two primary studies were included, with a range of study designs, methodological quality, pre-treatment variables, interventions and outcome measures. From the limited evidence available, survival appeared to increase when patients were selected by performance status (survival increasing from approximately three to seven months in high performance status groups, as defined by Karnofsky performance status or Recursive Partitioning Analysis classification). The evidence suggests no survival benefit when patients with poor performance status were treated with whole brain radiotherapy. No studies undertook direct measurement of patients' quality of life. Surrogate measures of patients' quality of life, such as improvement in neurological function or improvement/maintenance of KPS > or =70, produced response rates ranging from 7 to 90%. The heterogeneity of study designs, quality and outcomes necessitates caution in interpreting the review findings. WBRT appears to be of benefit in higher performance status patients but not in low performance status patients. This suggests a basis for current practice, however further robust trial evidence is required.


Aromatase expression in the cerebellum of the dog infected with canine distemper virus.
Aromatase is the enzyme that catalyzes the biosynthesis of estrogens. It is implicated in neuroprotection.The present study investigated aromatase expression in the cerebellum of dogs infected with canine distemper virus (CDV), a disease characterized by demyelination in the white matter of the cerebellum. The presence of CDV infection was confirmed on the basis of histopathology and immunohistochemical localization of CDV antigen in glial cells of the white matter.The number of aromatase immunoreactive astrocytes were significantly (p < 0.05) higher in CDV-infected dogs compared to control dogs. The results suggest that astrocytes respond to invasion and persistence of CDV by means of increased estrogen production.The results also suggest that the high level of estrogen expression is maintained similarly throughout all stages of the disease since the number of aromatase immunoreactive astrocytes did not vary during the different stages of CDV infection.


Associations of genetic variants in ATP-binding cassette A1 and cholesteryl ester transfer protein and differences in lipoprotein subclasses in the multi-ethnic study of atherosclerosis.
ATP-binding cassette A1 (ABCA1) and cholesteryl ester transfer protein (CETP) play important roles in the reverse cholesterol transport pathway. The associations of ABCA1 and CETP polymorphisms with lipoprotein subclasses have not been extensively studied. We genotyped 2 ABCA1 and 5 CETP polymorphisms in 999 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) and studied their associations with HDL and LDL subclass particle concentrations, measured by nuclear magnetic resonance spectroscopy. ABCA1 and CETP polymorphisms were associated with different and distinct changes in lipoprotein subclass concentrations. The ABCA1 1051G/A AA genotype, previously found to be associated with cardioprotective effects in this cohort, was associated with a 5.5% higher concentration of small HDL particles (P = 0.024). The CETP TaqIB B2B2, -2505C/A AA, and -629C/A AA genotypes, previously demonstrated to lack cardioprotective effects, were associated with 15.2%, 15.4%, and 11.7% higher HDL cholesterol concentrations, respectively, and 36.5%, 40.7%, and 25.4% higher large HDL particle concentrations (P < 0.0001). The minor alleles of the A373P and R451Q polymorphisms were associated with lower large HDL particle concentrations. Our study of the influence of ABCA1 and CETP genetic variants on lipoprotein subclasses demonstrates the importance of interpreting lipoprotein subclasses within the context of the biochemical processes involved in the alterations. In the case of HDL, the study of subclass particle numbers and sizes may not be sufficiently informative. Assays for HDL function may be needed to supplement quantification of HDL cholesterol and HDL particle numbers and sizes.


Fascicular nerve stimulation and recording using a novel double-aisle regenerative electrode.
As artificial prostheses become more refined, they are most often used as a therapeutic option for hand amputation. By contrast to extra- or intraneural interfaces, regenerative nerve electrodes are designed to enable electrical interfaces with regrowing axonal bundles of injured nerves, aiming to achieve high selectivity for recording and stimulation. However, most of the developed designs pose an obstacle to the regrowth mechanisms due to low transparency and cause impairment to the nerve regeneration. Here we present the double-aisle electrode, a new type of highly transparent, non-obstructive regenerative electrode. Using a double-side thin-film polyimide planar multi-contact electrode, two nerve fascicles can regenerate without physical impairment through two electrically isolated aisles. We show that this electrode can be used to selectively record and stimulate fascicles, acutely as well as chronically, and allow regeneration in nerve gaps of several millimeters without impairment. This multi-aisle regenerative electrode may be suitable for neuroprosthetic applications, such as prostheses, for the restoration of hand function after amputation or severe nerve injuries.


Processing of DNA for nonhomologous end-joining by cell-free extract.
In mammalian cells, nonhomologous end-joining (NHEJ) repairs DNA double-strand breaks created by ionizing radiation and V(D)J recombination. We have developed a cell-free system capable of processing and joining noncompatible DNA ends. The system had key features of NHEJ in vivo, including dependence on Ku, DNA-PKcs, and XRCC4/Ligase4. The NHEJ reaction had striking properties. Processing of noncompatible ends involved polymerase and nuclease activities that often stabilized the alignment of opposing ends by base pairing. To achieve this, polymerase activity efficiently synthesized DNA across discontinuities in the template strand, and nuclease activity removed a limited number of nucleotides back to regions of microhomology. Processing was suppressed for DNA ends that could be ligated directly, biasing the reaction to preserve DNA sequence and maintain genomic integrity. DNA sequence internal to the ends influenced the spectrum of processing events for noncompatible ends. Furthermore, internal DNA sequence strongly influenced joining efficiency, even in the absence of processing. These results support a model in which DNA-PKcs plays a central role in regulating the processing of ends for NHEJ.


Prehospital Electrolyte Care: A Review of Symptoms, Evaluation, and Management.
Ongoing evolution of prehospital medical care continues to advance beyond tactical field care scenarios in the consideration of prolonged field care. This is even more important to consider in theaters with extended evacuation times and limited local medical assets. The critical regulatory functions of electrolytes such as sodium, potassium, calcium, and glucose require medics operating in these environments to have a strong, fundamental knowledge of the principles, manifestations, and initial stabilization measures to aid their patients prior to, or in lieu of evacuation. Continued development and access to point of care testing in increasingly forward deployed settings further enables medics to perform these tasks. Here, we provide a brief review of these vital electrolytes, as well as additional kidney function evaluation considerations, to assist medics in their treatment efforts. Specific concerns for battlefield and atraumatic presentations are addressed.


Smoking and mortality from tuberculosis and other diseases in India: retrospective study of 43000 adult male deaths and 35000 controls.
In India most adult deaths involve vascular disease, pulmonary tuberculosis, or other respiratory disease, and men have smoked cigarettes or bidis (which resemble small cigarettes) for several decades. The study objective was to assess age-specific mortality from smoking among men (since few women smoke) in urban and in rural India. We did a case-control study of the smoking habits of 27000 urban and 16000 rural men who had died in the state of Tamil Nadu, southern India, from medical causes (ie, any cause other than accident, homicide, or suicide), and of 20000 urban and 15000 rural male controls. The main analyses are of mortality at ages 25-69 years. In the urban study area, the death rates from medical causes of ever smokers were double those of never smokers (standardised risk ratio at ages 25-69 years 2.1 [95% CI 2.0-2.2]). The risks were substantial both for cigarette smoking (the main urban habit) and for bidi smoking. Of this excess mortality among smokers, a third involved respiratory disease, chiefly tuberculosis (4.5 [4.0-5.0], smoking-attributed fraction 61%), a third involved vascular disease (1.8 [1.7-1.9], smoking-attributed fraction 24%), 11% involved cancer (2.1 [1.9-2.4], smoking-attributed fraction 32%), chiefly of the respiratory or upper digestive tracts, and 14% involved alcoholism or cirrhosis (3.3 [2.9-3.8], not attributed to smoking). Among ever smokers, the absolute excess mortality from tuberculosis was substantial throughout the age range 25-69 years. (A separate survey of 250000 men living in the urban study area found that ever smokers are three times as likely as never smokers to report a history of tuberculosis, corresponding to a higher rate of progression of chronic subclinical infection to clinical disease.) The proportional excesses of respiratory, vascular, and neoplastic mortality at ages 25-69 years among ever smokers in the urban study area were replicated, each with similarly narrow CI for the risk ratio, in the rural study area (where bidi smoking predominated), and are taken to be largely or wholly causal. For urban and for rural death from medical causes at older ages (> or =70 years), the standardised risk ratio was 1.3. Smoking, which increases the incidence of clinical tuberculosis, is a cause of half the male tuberculosis deaths in India, and of a quarter of all male deaths in middle age (plus smaller fractions of the deaths at other ages). At current death rates, about a quarter of cigarette or bidi smokers would be killed by tobacco at ages 25-69 years, those killed at these ages losing about 20 years of life expectancy. Overall, smoking currently causes about 700000 deaths per year in India, chiefly from respiratory or vascular disease: about 550000 men aged 25-69 years, about 110000 older men, and much smaller numbers of women (since few women smoke).


A paediatric telecardiology service for district hospitals in south-east England: an observational study.
To compare caseloads of new patients assessed by paediatric cardiologists face-to-face or during teleconferences, and assess NHS costs for the alternative referral arrangements. Prospective cohort study over 15 months. Four district hospitals in south-east England and a London paediatric cardiology centre. Babies and children. A telecardiology service introduced alongside outreach clinics. Clinical outcomes and mean NHS costs per patient. 266 new patients were studied: 75 had teleconsultations (19 of 42 newborns and 56 of 224 infants and children). Teleconsultation patients generally were younger (49% being under 1 year compared with 32% seen personally (p = 0.025)) and their symptoms were not as severe. A cardiac intervention was undertaken immediately or planned for five telemedicine patients (7%) and 30 conventional patients (16%). However, similar proportions of patients were discharged after being assessed (32% telemedicine and 39% conventional). During scheduled teleconferences the mean duration of time per patient in sessions involving real-time echocardiography was 14.4 min, and 8.5 min in sessions where pre-recorded videos were transmitted. Mean cost comparisons for telemedicine and face-to-face patients over 14-day and 6-month follow-up showed the telecardiology service to be cost-neutral for the three hospitals with infrequently-held outreach clinics (1519 UK pounds vs 1724 UK pounds respectively after 14 days). Paediatric cardiology centres with small cadres of specialists are under pressure to cope with ever-expanding caseloads of new patients with suspected anomalies. Innovative use of telecardiology alongside conventional outreach services should suitably, and economically, enhance access to these specialists.


Impact of chloramination on the development of laboratory-grown biofilms fed with filter-pretreated groundwater.
This study evaluated the continuous impact of monochloramine disinfection on laboratory-grown biofilms through the characterization of biofilm architecture and microbial community structure. Biofilm development and disinfection were achieved using CDC (Centers for Disease Control and Prevention) biofilm reactor systems with polyvinyl chloride (PVC) coupons as the substratum and sand filter-pretreated groundwater as the source of microbial seeding and growth nutrient. After 2 weeks of growth, the biofilms were subjected to chloramination for 8 more weeks at concentrations of 7.5±1.4 to 9.1±0.4 mg Cl2 L(-1). Control reactors received no disinfection during the development of biofilms. Confocal laser scanning microscopy and image analysis indicated that chloramination could lead to 81.4-83.5% and 86.3-95.6% reduction in biofilm biomass and thickness, respectively, but could not eliminate biofilm growth. 16S rRNA gene terminal restriction fragment length polymorphism analysis indicated that microbial community structures between chloraminated and non-chloraminated biofilms exhibited different successional trends. 16S rRNA gene pyrosequencing analysis further revealed that chloramination could select members of Actinobacteria and Acidobacteria as the dominant populations, whereas natural development leads to the selection of members of Nitrospira and Bacteroidetes as dominant biofilm populations. Overall, chloramination treatment could alter the growth of multi-species biofilms on the PVC surface, shape the biofilm architecture, and select a certain microbial community that can survive or proliferate under chloramination.


Aqueous stabilisation of carbon-encapsulated superparamagnetic α-iron nanoparticles for biomedical applications.
Carbon-based nanomaterials, such as carbon-encapsulated magnetic nanoparticles (CEMNP, core@shell), show a wide range of desirable properties for applications in the biomedical field (clinical MRI, hyperthermia), for energy production and storage (hydrogen storage), for the improvement of electronic components and for environmental applications (water-treatment). However, this kind of nanoparticle tends to aggregate in water suspensions. This often hampers the processability of the suspensions and presents an obstacle to their application in many fields. Here the stabilisation of core-shell Fe-C nanoparticles by surface adsorbed polyvinyl-alcohol (PVA) is presented. Different PVA/CEMNP mass ratios (9, 36, 144 and 576 w/w) were studied. Several characterisation techniques were used in order to determine the size distribution of the particles and to optimize the PVA/CEMNP ratio. A good colloidal stability was obtained for spherical nanoparticles about 50 nm in diameter containing several superparamagnetic Fe cores. The nanoparticles were found to be isolated and well dispersed in solution. The use of PVA for coating carbon-encapsulated Fe nanoparticles does not only result in a good colloidal stability in aqueous suspensions, but the resulting particles also show low cytotoxicity and an interesting cell internalization behaviour. The simple stabilization method developed here can likely be extended to other core@shell nanoparticle systems as well as other carbon-based nanomaterials in the future.


Vector abundance and malaria transmission in rice-growing villages in Mali.
Anophelism without malaria has long been recognized. In large irrigation projects, such as that around Niono, Mali, villages in irrigated areas sometimes have more anopheline vectors of malaria than adjacent nonirrigated villages, but overall malaria prevalence is substantially less. One hypothesized explanation for this is high anopheline densities lead to smaller adults, who do not live so long and hence are less efficient at transmitting the disease. We analyzed serial collections from 18 villages in an irrigated area of Mali, measuring correlations between mosquito densities and survival rates, zoophilic rates, and vectorial capacity over the villages and times. Adult density was inversely related to anthropophily and adult survival and its relationship with vectorial capacity was positive at low mosquito densities, flat at intermediate densities, and negative at high densities. This may partly explain why malaria prevalence is low in irrigated villages with high Anopheles density.


Ambivalence in Older Parent-Adult Child Relationships: Mixed Feelings, Mixed Measures.
This research compared direct and indirect measures of ambivalence, 2 commonly used strategies for measuring intergenerational ambivalence between older parents and their adult children. Directly and indirectly measured ambivalence, corresponding to felt and potential manifestations of the construct, were contrasted with each other and across generations. Data were derived from 253 older parent-adult child dyads participating in the Longitudinal Study of Generations in 2005. Direct and indirect measures of ambivalence were moderately correlated with each other within each generation. Children expressed greater indirect ambivalence than their parents but were no different than their mothers or fathers in their levels of direct ambivalence. Multivariate regression analyses examining the relationship between each type of ambivalence with individual and relationship characteristics found differences in associations across equations. The results suggest that direct and indirect measures are related but represent 2 distinct conceptions of ambivalence. This research highlights the challenges in understanding the full complexity of intergenerational relations and suggests that both generational perspectives be considered in future research.


Postural loads during walking after an imbalance of occlusion created with unilateral cotton rolls.
It was showed that stomatognathic functions correlate with alterations in locomotion, that are detectable through the analysis of loading during walking. For example, subjects with symptoms of Temporomandibular disorders (TMDs) showed a significant higher load pressure on the two feet, respect to health subjects, when cotton rolls were inserted. This previous study appeared to suggest that the alteration of postural loads associated to a particular alteration of stomatognathic condition (in this case, the cotton rolls inserted between the two dental arches) is detectable only in TMD's subjects, while it resulted not detectable in health subjects, because in that study, health subjects did not show any significant alteration of postural loads related to the different stomatognathic tested conditions. In other words, in that previous study, in the group of health subjects, no significant difference in postural loads was observed among the different test conditions; while TMD subjects showed a significant higher load pressure on the two feet when cotton rolls were inserted, respect to all the other tested conditions. Thus, the aim of this study was to better investigate these correlations in health subjects without TMD's symptoms, testing other different intra-oral conditions, and to verifywhether an experimentally induced imbalance of occlusion, obtained putting an unilateral cotton roll, could cause an alteration of postural loading on feet during walking. In a sample of thirty Caucasian adult females (mean age 28.5 +/- 4.5), asymptomatic for TMDs, when a cotton roll was positioned on the left or the right sides of dental arches, so causing a lateral shift of the mandible, the percentage of loading and the loading surface of the ipsi-lateral foot, left or right, were found to be significantly lower than in habitual occlusion (p < 0.05). Males were not included because of their different postural attitude respect to females. Further studies in a sample of males will be presented. This study showed that in health subjects without TMD's symptoms, an experimentally induced imbalance of the occlusion, obtained through an unilateral cotton roll, is associated to detectable alterations in the distribution of loading on feet surface, during walking.


Orbicularis oculi muscle fibers are relatively short and heterogeneous in length.
The anatomy of individual myofibers within the orbicularis oculi muscle was examined to determine individual myofiber lengths in the different regions of the muscle. A wide variety of eyelid conditions require eyelid surgery or drug injections directly into the eyelid. Knowledge of regional myofiber anatomy and physiology is important for accurate treatment of these conditions. Eyelid specimens from rabbits were treated with collagenase, fixed, and stained for neuromuscular junction location. Individual myofibers were dissected from these muscle specimens and were measured to determine individual myofiber length and neuromuscular junction position. Additional eyelid specimens of rabbits and humans were stained en bloc to visualize neuromuscular junction location in the pretarsal and preseptal regions of the orbicularis oculi muscle. The myofibers showed variable lengths, shorter in the pretarsal region of the muscle and longer in the preseptal region. The average individual myofiber length in the pretarsal region was 36% as long as the entire length of the pretarsal muscle region. In the preseptal region, the myofibers were slightly longer, covering 54% of the entire length of this region of the muscle. In both the pretarsal and preseptal regions of the rabbit and human orbicularis oculi muscle, there were many clusters of neuromuscular junctions throughout the medial to lateral length of the muscle, with the majority of the neuromuscular junctions in the medial and lateral canthal regions of the preseptal portion of the lid. This indicates that the muscle is composed of relatively short, overlapping myofibers, and that the shortest myofibers reside in the medial and lateral canthal regions of the eyelid. Multiple innervation of one rabbit myofiber was observed as a rare occurrence. Individual myofibers of the orbicularis oculi muscle are relatively short, end intrafascicularly, and are of heterogeneous lengths varying regionally within the muscle. Thus, for drug injections into the eyelid, optimal drug effectiveness may require treatment of the entire lid from medial to lateral canthus to overcome the tissue barriers to diffusion. The existence of muscle fibers of heterogeneous lengths suggests that the complex organization of muscle fibers may play previously unappreciated but important roles in normal function, pathophysiology, and age-related changes in the eyelid.


Small medial meniscocapsular separations: a potential cause of chronic medial-side knee pain.
To describe clinical characteristics, surgical findings, and functional outcome after arthroscopic repair of a unique type of meniscocapsular separation. We retrospectively reviewed office charts, magnetic resonance imaging (MRI) scans, operative reports, and arthroscopic images of 6 patients who underwent surgery between January 2007 and May 2009, in whom a medial meniscocapsular separation measuring less than 5 mm in length was identified and treated. Inclusion criteria were medial-side knee pain unresponsive to nonoperative management, negative MRI findings, and an isolated meniscocapsular separation injury detected on arthroscopy and repaired with 1 stitch. Patients were contacted and completed questionnaires that included subjective International Knee Documentation Committee, Tegner, and Marx scores. Of the 6 patients, 5 were female patients aged 14 to 18 years who were involved in sports. All patients recalled an acute twisting knee injury. Symptoms were related mainly to sports and were absent or very minimal during activities of daily living. On physical examination, the medial joint line was tender in all patients, whereas medial-side knee discomfort while squatting (i.e., baseball catcher's position) and McMurray tests were positive only in some. The negative MRI scans used a 3-T magnet in 5 cases and a 1.5-T magnet in 1 case. The duration of symptoms from injury to surgery was between 6 months and 9 years in 5 cases. On arthroscopy, all patients had a medial meniscocapsular separation measuring less than 5 mm in length that was identified when the tip of the arthroscopic probe was inserted into the lesion. This was repaired with a single all-inside stitch. The mean latest follow-up was 31 months (range, 15 to 38 months). The mean subjective International Knee Documentation Committee score was 87 at latest follow-up. Tegner and Marx scores showed that after surgery, 5 patients regained their preinjury level of activity. Meniscocapsular separation can involve a segment of less than 5 mm in length, be occult on MRI, be challenging to visualize on arthroscopy, and lead to chronic medial-side knee pain. Critical evaluation with a history, physical examination, and careful arthroscopic inspection of the medial meniscus can lead to appropriate treatment with a good to excellent outcome after repair. Level IV, therapeutic case series.


Allergic reactions to peanuts, tree nuts, and seeds aboard commercial airliners.
Minimal data exist on the prevalence and characteristics of in-flight reactions to foods. To characterize reactions to foods experienced by passengers aboard commercial airplanes and to examine information about flying with a food allergy available from airlines. Telephone questionnaires were administered to individuals in a peanut, tree nut, and seed allergy database who self-reported reactions aboard aircraft. Airlines were contacted to obtain information on food allergy policies. Forty-one of 471 individuals reported allergic reactions to food while on airplanes, including 4 reporting more than 1 reaction. Peanuts accounted for most of the reactions. Twenty-one individuals (51%) treated their reactions during flight. Only 12 individuals (29%) reported the reaction to a flight attendant. Six individuals went to an emergency department after landing, including 1 after a flight diversion. Airline personnel were notified of only 3 of these severe reactions. Comparison of information given to 3 different investigators by airline customer service representatives showed that inconsistencies regarding important information occurred, such as whether the airline regularly serves peanuts. In this group of mainly adults with severe nut/seed allergy, approximately 9% reported experiencing an allergic reaction to food while on board an airplane. Some reactions were serious and potentially life-threatening. Individuals commonly did not inform airline personnel about their experiences. In addition, the quality of information about flying with food allergies available from customer service departments is highly variable and, in some cases, incomplete or inaccurate.