The appearance of trigeminal ectopic ganglia within the surface ectoderm in the chick embryo.
Aberrant ganglion cell morphogenesis associated with the ophthalmic placode was observed within the epidermis of the chick embryo at stages 20 through 26. This process was studied using immunohistochemistry and scanning and transmission electron microscopy. Clusters of ganglion cells were covered by epidermis and seen as epidermal nodules distributed diffusely in the supraorbital region. The ganglion cell clusters found within these nodules were not delineated by basement membrane from the epidermis, and were provisionally termed ectopic ganglia. The cell bodies within the ganglia possessed neurites containing microtubules and neurofilament protein. The cell bodies were also immunoreactive to monoclonal antibodies, E/C8 and HNK-1, indicating neuronal phenotypes. The neurites were often associated with the ophthalmic nerve or its branches as well as being distributed in the ectoderm. The ectopic ganglia seemed to represent the delayed gangliogenesis of a part of the ophthalmic placode which failed to detach from the ectoderm during ophthalmic ganglion formation.


Magnetic resonance imaging abnormalities as a marker of multiple system atrophy in isolated rapid eye movement sleep behavior disorder.
Patients with isolated rapid eye movement (REM) sleep behavior disorder (IRBD) develop Parkinson disease (PD), dementia with Lewy bodies (DLB), or multiple system atrophy (MSA). Magnetic resonance imaging (MRI) is abnormal in MSA showing abnormalities in the putamen, cerebellum, and brainstem. Our objective was to evaluate the usefulness of MRI to detect MRI abnormalities in IRBD and predict development of MSA and not PD and DLB. In IRBD patients that eventually developed PD, DLB, and MSA, we looked for the specific structural MRI abnormalities described in manifest MSA (e.g. hot cross-bun sign, putaminal rim, and cerebellar atrophy). We compared the frequency of these MRI changes among groups of converters (PD, DLB, and MSA) and analyzed their ability to predict development of MSA. The clinical and radiological features of the IRBD patients that eventually converted to MSA are described in detail. A total of 61 IRBD patients who underwent MRI phenoconverted to PD (n = 30), DLB (n = 26), and MSA (n = 5) after a median follow-up of 2.4 years from neuroimaging. MRI changes typical of MSA were found in four of the five (80%) patients who converted to MSA and in three of the 56 (5.4%) patients who developed PD or DLB. MRI changes of MSA had sensitivity of 80.0%, specificity of 94.6%, positive likelihood ratio of 14.9 (95% CI 4.6-48.8), and negative likelihood ratio of 0.2 (95% CI 0.04-1.2) to predict MSA. In IRBD, conventional brain MRI is helpful to predict conversion to MSA. The specific MRI abnormalities of manifest MSA may be detected in its premotor stage.


Aging causes distinct characteristics of polyglutamine amyloids in vivo.
Polyglutamine diseases, including Machado-Joseph disease and Huntington's disease, typically appear in midlife and are characterized by amyloid accumulations of abnormally expanded polyglutamine proteins. Although there is growing evidence that aging has an important role in the occurrence of such diseases, the role of aging in the late onset of these diseases is not well understood. Recent studies showed that differences in amyloid conformation from different brain regions lead to differing toxicity. We hypothesized that higher amyloid toxicity at later ages might cause the late onset of polyglutamine diseases. Using a method for temporal and regional gene expression targeting (TARGET) in Drosophila, we showed that transient polyglutamine expression caused more severe neurodegeneration in older flies than in younger flies. Moreover, the polyglutamine amyloids themselves showed distinct characteristics in relation to age; those from older flies were less resistant to SDS and more effective at seeding polymerization than those from younger flies, suggesting that the polyglutamine amyloids in aged individuals may have higher toxicity. These findings show that age-related changes in amyloid characteristics may be a trigger for late-onset polyglutamine diseases.


Relationship of the epidermal growth factor-receptor to the growth fraction (Ki-67 antibody) and the flow cytometric S-phase as cell kinetics parameters, in human mammary carcinomas.
Epidermal growth factor (EGF) has been shown to have a mitogenic effect on some breast cancer cells lines in vitro. The growth of the subclass of human breast tumors which expresses the specific receptor for EGF seems to be mediated by autocrine mechanisms rather than steroid hormones. The expression of EGF-receptor, as detected by an immunocytochemical method, was compared with the Growth Fraction (GF) by the Ki-67 monoclonal antibody and the S-phase content as tumor proliferative activity indexes, and with DNA ploidy and some pathologic features in 86 stage I-II breast carcinomas. Overall 52 out of 86 (60%) of the tumors were EGF-receptor positive. There was no correlation between the cell kinetics parameters and the EGF-receptor status, suggesting that its expression may be unrelated to the proliferative activity of the tumor in these clinical stages and that the EGF-receptor GF and S-phase may be independent variables in breast cancer. In our series 57% of tumors were DNA aneuploid and only a trend was found towards EGF-receptor positivity (P = 0.08). There was no correlation between EGF-receptor expression and grading or node-status. The overall picture is that of an independent relationship between EGF-receptor with the cell kinetics parameters and ploidy, confirming the complex and heterogeneous biology of breast carcinoma. These results suggest the possibility of better recognition of subsets of patients with diverse tumor aggressiveness, combining together EGF-receptor status, cell kinetics and ploidy, with a better stratification for treatment options.


The length of homology required for gene targeting in embryonic stem cells.
Homologous recombination has been used to introduce site-specific mutations into murine embryonic stem (ES) cells with both insertion and replacement vectors. In this study, we compared the frequency of gene targeting with various lengths of homology and found a dramatic increase in targeting with an increase in homology from 1.3 to 6.8 kb. We examined in detail the relationship between the length of homology and the gene-targeting frequency for replacement vectors and found that a critical length of homology is needed for targeting. Adding greater lengths of homology to this critical length has less of an effect on the targeting frequency. We also analyzed the lengths of homology necessary on both arms of the vector for gene replacement events and found that 472 bp of homology is used as efficiently as 1.2 kb in the formation and resolution of crossover junctions.


Characterization and formulation of multiple epitope-specific neutralizing monoclonal antibodies for passive immunization against cryptosporidiosis.
The coccidian parasite Cryptosporidium parvum causes diarrhea in humans, calves, and other mammals. Neither immunization nor parasite-specific pharmaceuticals that are consistently effective against this organism are available. While polyclonal antibodies against whole C. parvum reduce infection, their efficacy and predictability are suboptimal. We hypothesized that passive immunization against cryptosporidiosis could be improved by using neutralizing monoclonal antibodies (MAbs) targeting functionally defined antigens on the infective stages. We previously reported that the apical complex and surface-exposed zoite antigens CSL, GP25-200, and P23 are critical in the infection process and are therefore rational targets. In the present study, a panel of 126 MAbs generated against affinity-purified CSL, GP25-200, and P23 was characterized to identify the most efficacious neutralizing MAb formulation targeting each antigen. To identify neutralizing MAbs, sporozoite infectivity following exposure to individual MAbs was assessed by enzyme-linked immunosorbent assay. Of 126 MAbs evaluated, 47 had neutralizing activity. These were then evaluated individually in oocyst-challenged neonatal mice, and 14 MAbs having highly significant efficacy were identified for further testing in formulations. Epitope specificity assays were performed to determine if candidate MAbs recognized the same or different epitopes. Formulations of two or three neutralizing MAbs, each recognizing distinct epitopes, were then evaluated. A formulation of MAbs 3E2 (anti-CSL [alphaCSL]), 3H2 (alphaGP25-200), and 1E10 (alphaP23) provided highly significant additive efficacy over that of either individual MAbs or combinations of two MAbs and reduced intestinal infection by 86 to 93%. These findings indicate that polyvalent neutralizing MAb formulations targeting epitopes on defined antigens may provide optimal passive immunization against cryptosporidiosis.


[Animal experiments on ozone therapy of non-irradiated and irradiated tumors. II. Ehrlich ascites carcinoma in vivo].
Mice, carriers of the Ehrlich ascites carcinoma, were exposed to a fractionated whole-body irradiation with four times 750 R. Before resp. after each exposure, an ozone-oxygen mixture was intraperitoneally injected. In other cases, the ozone-oxygen mixture was given without irradiation. Ozone had no essential effect upon the transplantation capacity neither in irradiated ascites cells nor in cells not exposed to radiation. Ehrlich ascites tumor cells, transplanted into a subcutaneous air-pocket under the abdominal skin of the mouse, developed a solid tumor and a fluid accumulation without cells. A diminution of the fluid was brought about by means of a fractionated local irradiation with five times 200R, by a secondary treatment with ozone and also by ozone alone. Evidence of damage to the tumor cells, however, is only to be produced by investigations into the metabolism and reproductive capacity of these cells.


A practice-based randomised controlled trial of the efficacy of three interventions to reduce dentinal hypersensitivity.
The aim of this study was to evaluate the efficacy of three different interventions (non-desensitising toothpaste, desensitising toothpaste and professionally applied dentine bonding agent) in reducing dentinal hypersensitivity over a 2-week, 3-month and 6-month-period in a dental practice setting. This was a randomised controlled, single-blind; parallel-group trial conducted in general dental practice by a single general dental practitioner. Seventy-five subjects were randomly allocated to three groups; non-desensitising toothpaste (NDT), desensitising toothpaste (DT) and professionally applied desensitising agent (DA). Dentinal hypersensitivity was measured using a Visual Analogue Scale (VAS) to record the response from a standardised short blast of air from a triple syringe. Dentinal hypersensitivity was recorded at baseline, two weeks, three months and six months for all groups. Dentinal hypersensitivity reduced significantly (p<0.0001) in both groups DT and DA, in addition the reduction in sensitivity was sustained and continued to improve over a 6-month-period. The greatest reduction in dentinal hypersensitivity was recorded in group DA. The results from this study suggest that application of dentine bonding agents, to teeth diagnosed with dentine hypersensitivity provides the greatest improvement in dentine hypersensitivity at 2 weeks and 6 months. This reduction in dentine hypersensitivity is greater than that achieved by the desensitising toothpaste tested and a non-desensitising toothpaste.


The influence of opsonins on the bactericidal effect of bovine alveolar macrophages against Pasteurella multocida.
Monolayers of bovine alveolar macrophages were infected with smooth and rough strains of Pasteurella multocida to determine their bactericidal function. Heat inactivated normal bovine serum, fresh bovine serum, specific immune serum and a combination of specific immune serum and fresh bovine serum were used as opsonins. A substantial difference in the bactericidal effect of macrophages against the logarithmic and stationary phase p. multocida was observed. Opsonization of the rough strain of P. multocida with the combination of specific immune and fresh serum increased their association with alveolar macrophages compared to those opsonized with either normal serum, fresh serum or specific immune serum. Opsonization of the smooth strain of P. multocida with normal bovine serum resulted in substantially fewer bacteria associated with macrophages at time zero, compared with other opsonins. Regardless of the kind of opsonins used in these experiments, the number of the rough strain of P. multocida killed by macrophages was always higher than those of the smooth strain.


Prevalence and predictors of metamorphopsia after successful rhegmatogenous retinal detachment surgery: a cross-sectional, comparative study.
To evaluate the prevalence of metamorphopsia after successful rhegmatogenous retinal detachment (RRD) surgery and determine the independent predictors of metamorphopsia. A cross-sectional, comparative study. The study included 380 eyes of 357 patients who underwent a successful RRD surgery between 2009 and 2015. The presence of metamorphopsia was tested with an Amsler grid and the foveal microstructure was scanned with high-resolution spectral-domain optical coherence tomography (OCT) at a follow-up visit. Medical records were reviewed for preoperative and intraoperative factors associated with postoperative visual recovery. The mean follow-up period was 35.1±19.6 months. The prevalence of metamorphopsia in our study was 46.58% (177/380), whereas in macula-off cases this number increased to 56.69% (144/254). Stepwise logistic regression analysis indicated that younger age at the diagnosis (OR=0.97, p<0.01), preoperative macula-off status (OR=3.34, p<0.01), postoperative presence of subretinal fluid (SRF) (OR=3.58, p=0.01) and disrupted external limiting membrane (ELM) junction (OR=1.79, p=0.02) were the independent predictors for metamorphopsia after surgery. The abnormal foveal microstructures after successful surgeries mainly included six types: disrupted inner segment/outer segment (133 eyes, 35.00%), disrupted ELM (131 eyes, 34.47%), epiretinal membrane (44 eyes, 11.58%), SRF (26 eyes, 6.84%), macular hole (9 eyes, 2.37%) and cystoid macular oedema (6 eyes, 1.58%). Considering metamorphopsia, special attention should be paid to young patients and/or the cases with involvement of macula. High-resolution OCT is informative in detecting anatomic abnormalities after RRD surgery. The postoperative presence of SRF and disrupted ELM line are independent predictors of metamorphopsia.


Pulmonary retransplantation: does the indication for operation influence postoperative lung function?
An international series of pulmonary retransplantation was updated to determine the factors associated with pulmonary function, bronchiolitis obliterans syndrome stage, and survival after operation. One hundred sixty patients underwent retransplantation in 35 centers from 1985 to 1995. Logistic regression methods were used to determine variables associated with 3-month and 2-year survival after retransplantation. Values of forced expiratory volume in 1 second were contrasted between groups by unpaired, two-tailed t tests. The median follow-up in surviving recipients was 780 days. Actuarial survival was 45% +/- 4%, 41% +/- 4%, and 33% +/- 4% at 1, 2, and 3 years, respectively. On multivariable analysis, the only predictor of 3-month survival was preoperative ambulatory status (p = 0.005), whereas center experience with at least five pulmonary retransplantations was the sole predictor of 2-year survival (p = 0.04). The prevalence of stage 3 (severe) bronchiolitis obliterans syndrome was 12% at 1 year, 15% at 2 years, and 33% at 3 years after retransplantation. Retransplant recipients with stage 3 bronchiolitis obliterans syndrome at 1 year had a significantly worse actuarial survival than those with stages 0 to 2 (p < 0.01). By 3 years after retransplantation, the forced expiratory volume in 1 second was significantly lower in patients who underwent reoperation because of obliterative bronchiolitis than in patients who underwent retransplantation because of acute graft failure or an airway complication (p = 0.02). Only 31% of patients who underwent retransplantation because of obliterative bronchiolitis were free of bronchiolitis obliterans syndrome at 3 years versus 83% of patients who underwent retransplantation because of other indications (p = 0.02). Preoperative ambulatory status predicts early survival and center volume predicts intermediate-term outcome after retransplantation. Improved management strategies are necessary to prevent the development of progressive graft dysfunction after retransplantation for obliterative bronchiolitis.


Limited dietary interventions in rural Australian communities: A systematic review.
This review aimed to synthesise the evidence on the effectiveness of dietary interventions targeting adolescents (>13 years) and adults living in rural or remote Australia. Six electronic databases were searched to identify dietary interventions undertaken in rural or remote communities. Studies were included if they utilised intervention and control comparisons or pre and post assessment of diet-related outcomes. If studies included metropolitan populations, dietary outcome measures had to be provided separately for rural data. In total, 14 articles from 12 unique studies met the criteria for inclusion and together provided incomplete coverage across all states of Australia, included intervention studies targeted diet to address obesity, cardiovascular disease, and high blood pressure or diabetes. No studies were focussed on reducing community malnutrition. All studies, with one exception, focussed specifically on rural adults, no interventions specifically targeted adolescents in rural areas. Only two studies documented the involvement of a dietitian in intervention development or delivery. All studies produced a significant outcome for either dietary intake, body mass index, waist circumference, or diet related biomedical risk factors for individuals located in rural or remote areas of Australia. Dietary interventions in rural Australia are under-studied, especially among the adolescent population. This is despite the high level of preventable diet-related disease burden in rural and remote Australia. Existing evidence shows promise in improving dietary intakes, but further, large scale intervention research, with the involvement of dietitians, is urgently needed to improve the health of rural communities.


Correlation Between Arthroscopy Simulator and Video Game Performance: A Cross-Sectional Study of 30 Volunteers Comparing 2- and 3-Dimensional Video Games.
To investigate the association between arthroscopy simulator performance and video game skills. This study compared the performances of 30 volunteers without experience performing arthroscopies in 3 different tasks of a validated virtual reality knee arthroscopy simulator with the video game experience using a questionnaire and actual performances in 5 different 2- and 3-dimensional (D) video games of varying genres on 2 different platforms. Positive correlations between knee arthroscopy simulator and video game performances (ρ = 0.63, P < .001) as well as experiences (ρ = 0.50, P = .005) were found. The strongest correlations were found for the task of catching (hooking) 6 foreign bodies (virtual rings; "triangulation") and the dribbling performance in a sports game and a first-person shooter game, as well as the meniscus resection and a tile-matching puzzle game (all ρ ≥ 0.60, P < .001). No correlations were found for any of the knee arthroscopy simulator tasks and a strategy game. Although knee arthroscopy performances do not correlate with 2-D strategy video game skills, they show a correlation with 2-D tile-matching puzzle games only for easier tasks with a rather limited focus, and highly correlate with 3-D sports and first-person shooter video games. These findings show that experienced and good 3-D gamers are better arthroscopists than nonexperienced and poor 3-D gamers. Level II, observational cross-sectional study.


[Association of HLA-A, B and DRB1 alleles with leukemia in Han population in Hunan Province].
To investigate the association of HLA-A, B, and DRB1 alleles with leukemia in the Han population in Hunan Province. HLA-A, B, and DRB1 alleles were genotyped in 105 patients with chronic myelocytic leukemia, 25 with acute lymphocytic leukaemia, and 48 with acute nonlymphocytic leukemia using polymerase chain reaction with sequence-specific primer (PCR-SSP). The hemopoietic stem cells from 3,664 unrelated normal individuals of Han nationality in Hunan were used as the control group. The phenotypic frequencies of HLA-B58, DR12, and DR14 were significantly higher in patients with chronic myelocytic leukemia than in the control group, with relative risk of 6.1287, 1.6519, and 1.6479, respectively. In patients with acute lymphocytic leukaemia, the phenotypic frequency of HLA-B58 was significantly higher than that in the control group, with the relative risk of 7.4055. In patients with acute nonlymphocytic leukemia, the frequencies of HLA-B58 and DR8 phenotypes were significantly higher but HLA-A24 frequency was significantly lower than those of the control group, with the relative risk of 13.9789, 2.2839, and 0.4012, respectively. HLA-B58, DR12, DR14 alleles appear to contribute to the genetic susceptibility of patients with chronic myelocytic leukemia. HLA-B58 allele can be associated with the genetic susceptibility for patients with acute lymphocytic leukaemia. In patients with acute nonlymphocytic leukemia, HLA-B58 and DR8 are probably the susceptible alleles whereas HLA-A24 allele may play a protective role.


Multiplexed colorimetric detection of Kaposi's sarcoma associated herpesvirus and Bartonella DNA using gold and silver nanoparticles.
Kaposi's sarcoma (KS) is an infectious cancer occurring most commonly in human immunodeficiency virus (HIV) positive patients and in endemic regions, such as Sub-Saharan Africa, where KS is among the top four most prevalent cancers. The cause of KS is the Kaposi's sarcoma-associated herpesvirus (KSHV, also called HHV-8), an oncogenic herpesvirus that while routinely diagnosed in developed nations, provides challenges to developing world medical providers and point-of-care detection. A major challenge in the diagnosis of KS is the existence of a number of other diseases with similar clinical presentation and histopathological features, requiring the detection of KSHV in a biopsy sample. In this work we develop an answer to this challenge by creating a multiplexed one-pot detection system for KSHV DNA and DNA from a frequently confounding disease, bacillary angiomatosis. Gold and silver nanoparticle aggregation reactions are tuned for each target and a multi-color change system is developed capable of detecting both targets down to levels between 1 nM and 2 nM. The system developed here could later be integrated with microfluidic sample processing to create a final device capable of solving the two major challenges in point-of-care KS detection.


Effect of CD8+ lymphocyte depletion on virus containment after simian immunodeficiency virus SIVmac251 challenge of live attenuated SIVmac239delta3-vaccinated rhesus macaques.
Although live attenuated vaccines can provide potent protection against simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus challenges, the specific immune responses that confer this protection have not been determined. To test whether cellular immune responses mediated by CD8+ lymphocytes contribute to this vaccine-induced protection, we depleted rhesus macaques vaccinated with the live attenuated virus SIVmac239Delta3 of CD8+ lymphocytes and then challenged them with SIVmac251 by the intravenous route. While vaccination did not prevent infection with the pathogenic challenge virus, the postchallenge levels of virus in the plasmas of vaccinated control animals were significantly lower than those for unvaccinated animals. The depletion of CD8+ lymphocytes at the time of challenge resulted in virus levels in the plasma that were intermediate between those of the vaccinated and unvaccinated controls, suggesting that CD8+ cell-mediated immune responses contributed to protection. Interestingly, at the time of challenge, animals expressing the Mamu-A*01 major histocompatibility complex class I allele showed significantly higher frequencies of SIV-specific CD8+ T-cell responses and lower neutralizing antibody titers than those in Mamu-A*01- animals. Consistent with these findings, the depletion of CD8+ lymphocytes abrogated vaccine-induced protection, as judged by the peak postchallenge viremia, to a greater extent in Mamu-A*01+ than in Mamu-A*01- animals. The partial control of postchallenge viremia after CD8+ lymphocyte depletion suggests that both humoral and cellular immune responses induced by live attenuated SIV vaccines can contribute to protection against a pathogenic challenge and that the relative contribution of each of these responses to protection may be genetically determined.


Probability-enhanced sufficient dimension reduction for binary classification.
In high-dimensional data analysis, it is of primary interest to reduce the data dimensionality without loss of information. Sufficient dimension reduction (SDR) arises in this context, and many successful SDR methods have been developed since the introduction of sliced inverse regression (SIR) [Li (1991) Journal of the American Statistical Association 86, 316-327]. Despite their fast progress, though, most existing methods target on regression problems with a continuous response. For binary classification problems, SIR suffers the limitation of estimating at most one direction since only two slices are available. In this article, we develop a new and flexible probability-enhanced SDR method for binary classification problems by using the weighted support vector machine (WSVM). The key idea is to slice the data based on conditional class probabilities of observations rather than their binary responses. We first show that the central subspace based on the conditional class probability is the same as that based on the binary response. This important result justifies the proposed slicing scheme from a theoretical perspective and assures no information loss. In practice, the true conditional class probability is generally not available, and the problem of probability estimation can be challenging for data with large-dimensional inputs. We observe that, in order to implement the new slicing scheme, one does not need exact probability values and the only required information is the relative order of probability values. Motivated by this fact, our new SDR procedure bypasses the probability estimation step and employs the WSVM to directly estimate the order of probability values, based on which the slicing is performed. The performance of the proposed probability-enhanced SDR scheme is evaluated by both simulated and real data examples.


Hyperglycemia and diabetes mellitus are related to vestibular organs dysfunction: truth or suggestion? A literature review.
Diabetes mellitus is an independent risk factor for falling, particularly in the elderly. Due to chronic hyperglycemia and hyperinsulinemia patients with diabetes mellitus may have neurological deficits as peripheral neuropathy that is a debilitating micro-vascular complication affecting the proximal and distal peripheral sensory and motor nerves. Sensory neuropathy is prominent and represents the chief contributor to postural instability in diabetic subjects. Diabetic retinopathy is another complication consequent to a breakdown of the inner blood-retinal barrier with accumulation of extracellular fluids in the macula and growth of new vessels causing retinal detachment. Together peripheral neuropathy and retinopathy contribute to increase the risk of falls in diabetic patients, but a certain vestibular organs impairment should not be underestimated. Nevertheless, the exact mechanism and localization of peripheral vestibular damage consequent to chronic hyperglycemia and hyperinsulinemia are currently not still understood. Moreover it is not defined the possible role of these two blood conditions in worsening the prognosis of typical vestibular pathologies like "benign paroxysmal positional vertigo" and "Meniere disease". The aim of this review was to retrieve all studies investigating about the balance system alterations in patients suffering of diabetes. A search thorough Ovid MEDLINE was performed to enroll all eligible articles. Fourteen studies comprising a total of 1364 patients were included and analyzed in detail. On the basis of data reported in our review it appears plausible to hypothesize a direct connection among chronic hyperglycemic/hyperinsulinemic damage and peripheral vestibular organ dysfunction.


Effect of age of turkeys on the metabolisable energy of different foodstuffs.
1. True metabolisable energy (TME) of various foodstuffs were determined in turkeys at 3, 9 and 17 weeks of age. 2. TME of soyabean meal did not change with age but TME of wheat and maize was 13% higher in 17-week-old turkeys than in 3- and 9-week-old birds. 3. These differences should be taken into account when formulating diets for turkeys.


Chinese truck drivers' attitudes toward feedback by technology: a quantitative approach.
This study examined Chinese truck drivers' attitudes toward receiving feedback about their driving performance by in-cab technology and explored the best ways of providing feedback to truck drivers in China. The similarities and differences between US and Chinese drivers were also compared. Survey data were collected from 200 long-haul truck drivers in China to provide quantitative information. The results of the current study were compared to the results of a previous study published in 2006 which utilized focus group discussions with Chinese truck drivers, and to the data of a similar survey conducted in the US and published in 2005. Results of the current study showed that Chinese truck drivers were eager for more feedback about their driving performance and they were willing to receive feedback from technology. Although negative feedback was most prevalent in their working environment and was considered acceptable if it improves driving safety, they considered positive feedback as more helpful to safe driving. They perceived many benefits of receiving feedback by technology and comparatively few drawbacks and concerns. Compared to US truck drivers who strongly preferred feedback from a human (e.g., safety director, dispatcher) rather than from technology, Chinese truck drivers were more positive in terms of receiving feedback from technology. They considered feedback from technology to be more objective and scientific than feedback from humans. This study showed the importance of considering cross-culture differences when planning to apply interventions in different countries and cultures.


Allopurinol mouthwashes and 5-fluorouracil induced oral toxicity.
Allopurinol has been shown to decrease the gastro-intestinal and bone marrow toxicity of 5-fluorouracil. In an attempt to diminish mucositis resulting from 5-fluorouracil administration, whilst not affecting its systemic anti-tumour activity, an allopurinol mouthwash has been used. In six patients who experienced mucositis when treated initially with 5-fluorouracil, the use of an allopurinol mouthwash with subsequent courses resulted in a reduction of oral toxicity.


Water intake without the act of drinking.
A method is described that allows a rat to ingest fluid through a chronic gastric tube that bypasses the oropharyngeal cavity. In this situation longterm regulation of water intake occurs in normal rats and in the rat with diabetes insipidus. Under special circumstances, a remarkable degree of excess intake can be produced.


Rapid enzyme-linked immunosorbent assay for the diagnosis of human brucellosis in surveillance and clinical settings in Egypt.
To optimize and standardize an enzyme-linked immunosorbent assay (ELISA) for rapid diagnosis of human brucellosis in clinical cases identified during a surveillance study for acute febrile illness (AFI). Serum samples from patients presenting with AFI at 13 fever hospitals across Egypt between 1999 and 2003 were kept frozen at NAMRU-3 and used in this study. The assay was evaluated in 5 subject groups: brucellosis cases confirmed by blood culture (group I, n=202) 87% positive by standard tube agglutination test (TA), brucellosis cases exclusively confirmed by TA (group II, n=218), blood cultures from AFI cases positive for bacterial species other than Brucella (group III, n=103), AFI cases with unexplained etiologies (group IV, n=654), and healthy volunteers (group V, n=50). All members of groups III-V were negative for brucellosis by TA. Sensitivity and specificity of ELISA for total specific antibodies were >=96% versus 87% for TA as compared to microbial culture, the current gold standard method for Brucella identification. Assessment of Brucella antibody classes by ELISA in random subsets of the 5 groups showed significantly high (p>0.001) levels of anti Brucella IgG (>=81%) and IgM (>=90%) in groups I and II only. The obtained sensitivity and specificity results indicate that our ELISA is more suitable for AFI surveillance and clinical settings than blood culture and TA. The developed assay is also cost-effective, easier to use, faster, and the coated plates can be stocked for at least 8 months, providing a potential for field use and automation.


Improved KCN medium.
A semisolid tetrazolium salt agar medium developed for testing sensitivity to KCN is easier to interpret, has a longer storage life, and is less critical in the size of inoculum than is Moeller KCN broth medium.


Comparative genomics and transcriptomics in ants provide new insights into the evolution and function of odorant binding and chemosensory proteins.
The complex societies of ants and other social insects rely on sophisticated chemical communication. Two families of small soluble proteins, the odorant binding and chemosensory proteins (OBPs and CSPs), are believed to be important in insect chemosensation. To better understand the role of these proteins in ant olfaction, we examined their evolution and expression across the ants using phylogenetics and sex- and tissue-specific RNA-seq. We find that subsets of both OBPs and CSPs are expressed in the antennae, contradicting the previous hypothesis that CSPs have replaced OBPs in ant olfaction. Both protein families have several highly conserved clades with a single ortholog in all eusocial hymenopterans, as well as clades with more dynamic evolution and many taxon-specific radiations. The dynamically evolving OBPs and CSPs have been hypothesized to function in chemical communication. Intriguingly, we find that seven members of the conserved clades are expressed specifically in the antennae of the clonal raider ant Cerapachys biroi, whereas only one dynamically evolving CSP is antenna specific. The orthologs of the conserved, antenna-specific C. biroi genes are also expressed in antennae of the ants Camponotus floridanus and Harpegnathos saltator, indicating that antenna-specific expression of these OBPs and CSPs is conserved across ants. Most members of the dynamically evolving clades in both protein families are expressed primarily in non-chemosensory tissues and thus likely do not fulfill chemosensory functions. Our results identify candidate OBPs and CSPs that are likely involved in conserved aspects of ant olfaction, and suggest that OBPs and CSPs may not rapidly evolve to recognize species-specific signals.


Thioredoxin-1 and its mimetic peptide improve systolic cardiac function and remodeling after myocardial infarction.
Myocardial infarction (MI) is characterized by a significant loss of cardiomyocytes (CMs), and it is suggested that reactive oxygen species (ROS) are involved in cell cycle arrest, leading to impaired CM renewal. Thioredoxin-1 (Trx-1) scavenges ROS and may play a role in restoring CM renewal. However, the truncated form of Trx-1, Trx-80, can compromise its efficacy by exerting antagonistic effects. Therefore, a Trx-1 mimetic peptide called CB3 was tested as an alternative way to restore CMs. This study aimed to investigate the effects of Trx-1, Trx-80, and CB3 on mice with experimental MI and study the underlying mechanism of CB3 on CMs. Mouse cardiac parameters were quantified by echocardiography, and infarction size and fibrosis determined using Trichrome and Picro-Sirius Red staining. The study found that Trx-1 and CB3 improved mouse cardiac function, reduced the size of cardiac infarct and fibrosis, and decreased the expression of cardiac inflammatory markers. Furthermore, CB3 polarized macrophages into M2 phenotype, reduced apoptosis and oxidative stress after MI, and increased CM proliferation in cell culture and in vivo. CB3 effectively protected against myocardial infarction and could represent a new class of compounds for treating MI.


[Relationship between the systolic-diastolic shock index and mortality in myocardial infarction].
In the emergency room, the shock index was applied to determine the prognosis in various pathologies, such as acute infarction. The shock index is the re-sult of dividing heart rate by the systolic blood pressure. To determine the relationship between the systolic shock index and the di-astolic shock index as prognostic factors for mortality in acute myocardial infarction with ST segment elevation prior to admission to the Hemodynamics Room. A prolective analytical cross-sectional study was carried out in patients who were admitted to the Hemodynamics Room for cardiac catheterization within a period of 5 months in 2022. The systolic shock index and diastolic shock index were included as independent variables and mortality was the dependent variable. SPSS, version 25, was used and Pearson's chi-square test was used as statistical test, with a p value < 0.05 being significant. 162 patients were analyzed and showed a diastolic shock index > 1.2143 with a sensitivity of 62.5% and a specificity of 77.4% with a p < 0.05. Their systolic shock in-dex was > 0.8908 with a sensitivity of 45.8% and specificity of 91.2%, with a p < 0.05. It was determined that both shock indices are related as mortality prognos-tic factors in acute myocardial infarction with ST elevation prior to admission to the He-modynamic Room.


A Co-Designed Active Video Game for Physical Activity Promotion in People With Chronic Obstructive Pulmonary Disease: Pilot Trial.
People with chronic obstructive pulmonary disease (COPD) who are less active have lower quality of life, greater risk of exacerbations, and greater mortality than those who are more active. The effectiveness of physical activity interventions may facilitate the addition of game elements to improve engagement. The use of a co-design approach with people with COPD and clinicians as co-designers may also improve the effectiveness of the intervention. The primary aim of this study is to evaluate the feasibility of a co-designed mobile game by examining the usage of the game, subjective measures of game engagement, and adherence to wearing activity trackers. The secondary aim of this study is to estimate the effect of the game on daily steps and daily moderate-to-vigorous physical activity (MVPA). Participants with COPD who were taking part in the co-design of the active video game (n=9) acted as the experiment group, spending 3 weeks testing the game they helped to develop. Daily steps and MVPA were compared with a control group (n=9) of participants who did not co-design or test the game. Most participants (8/9, 89%) engaged with the game after downloading it. Participants used the game to record physical activity on 58.6% (82/141) of the days the game was available. The highest scores on the Intrinsic Motivation Inventory were seen for the value and usefulness subscale, with a mean of 6.38 (SD 0.6). Adherence to wearing Fitbit was high, with participants in both groups recording steps on >80% of days. Usage of the game was positively correlated with changes in daily steps but not with MVPA. The co-designed mobile app shows promise as an intervention and should be evaluated in a larger-scale trial in this population.


[Electron-microscopic analysis of cytoarchitectonic disorders in the cerebral cortex in schizophrenia].
Microscopy and electron microscopy were used to examine foci of neuronal loss in the 2nd-3rd layers of the prefrontal cortex of the autopsy brain from 8 schizophrenic patients and 8 controls without any mental pathology. No signs of gliosis were identified. Foci of neuronal loss showed multiple accumulations of the thin bundles of unmyelinated fibers not discovered in the control, dystrophic-changed astrocytes, swollen dendrites free of microtubules. The changes in synapses on dendritic spines and shafts in these areas of neuropile were discovered to be functional and dystrophic in nature.


[The significance of testicular microlithiasis].
Testicular microlithiasis (TM) has been reported in up to 46% of men with testicular cancer. This has given rise to the suspicion that TM is a premalignant condition. In studies of healthy men there is, however, no association between TM and development of cancer. Nonetheless, patients with TM and contralateral testicular cancer, testicular atrophy, inhomogeneous parenchyma, infertility or a history of maldescensus are at increased risk of having carcinoma in situ (CIS) and cancer development. Men with TM and one or more of the above mentioned risk factors should be offered a testicular biopsy to rule out CIS.


Impact of medical academic genealogy on publication patterns: An analysis of the literature for surgical resection in brain tumor patients.
"Academic genealogy" refers to the linking of scientists and scholars based on their dissertation supervisors. We propose that this concept can be applied to medical training and that this "medical academic genealogy" may influence the landscape of the peer-reviewed literature. We performed a comprehensive PubMed search to identify US authors who have contributed peer-reviewed articles on a neurosurgery topic that remains controversial: the value of maximal resection for high-grade gliomas (HGGs). Training information for each key author (defined as the first or last author of an article) was collected (eg, author's medical school, residency, and fellowship training). Authors were recursively linked to faculty mentors to form genealogies. Correlations between genealogy and publication result were examined. Our search identified 108 articles with 160 unique key authors. Authors who were members of 2 genealogies (14% of key authors) contributed to 38% of all articles. If an article contained an authorship contribution from the first genealogy, its results were more likely to support maximal resection (log odds ratio = 2.74, p < 0.028) relative to articles without such contribution. In contrast, if an article contained an authorship contribution from the second genealogy, it was less likely to support maximal resection (log odds ratio = -1.74, p < 0.026). We conclude that the literature on surgical resection for HGGs is influenced by medical academic genealogies, and that articles contributed by authors of select genealogies share common results. These findings have important implications for the interpretation of scientific literature, design of medical training, and health care policy.


12-Month naturalistic outcomes of depressive disorders in Hong Kong's primary care.
In Asia, the role of primary care physicians (PCPs) in mental health delivery is not clearly defined and what happens to patients following a depressive episode remains poorly understood. To examine the 12-month naturalistic outcomes of depression in primary care and the impact of PCP identification. A cohort study was conducted. A total of 10179 adults were consecutively recruited from the waiting rooms of 59 PCPs across Hong Kong to complete a survey which screened for depression. Blinded doctors provided data on their diagnosis and management; 539 screened-positive and 3819 screened-negative subjects consented to telephone follow-up at 3, 6 and 12 months. Study instruments included Patient Health Questionnaire-9, Centre for Epidemiologic Studies Depression Scale 20 and Short-Form Health Survey Version 2.0 (SF-12v2) and self-reported mental health and primary care service use. 12-month remission rate was 60.31%. PCP detection had no association with remission. Identified patients had poorer health-related quality of life (HRQOL) at baseline but a faster rate of recovery in SF-12v2 mental component scores. PCP detection was associated with greater mental health service use at 12, 26 and 52 weeks, while GP consultation rates were only increased at 12 weeks. Over 1 year, ~60% of depressed patients experience symptom resolution, while 40% continue to suffer a chronic or remitting course of illness. Identification of depression by a PCP does not appear to affect remission of mood symptoms at 12 months, but is associated with a faster rate of recovery of HRQOL. PCP detection raises GP consultation rates temporarily however appears to enable more patients to access mental health services over 12 months.


Scoring system to improve cost effectiveness of open access endoscopy.
The introduction of an open access general practitioner endoscopy service may result in many unnecessary examinations being performed. In an attempt to prevent this, 235 patients attending for endoscopy were interviewed and the results analysed to determine which factors best discriminated between those with major disease (ulcers, cancers, oesophageal strictures; n = 48) and those without (n = 187). The six characteristics which best discriminated between the two groups were increasing age, history of vomiting, male sex, smoking, and a past history of peptic ulcer or hiatus hernia. With the use of these six features a scoring system was devised, designed to give an indication of the likelihood of finding such disease in an individual patient. This was assessed prospectively in a further 356 patients. The results showed that by utilising this scoring system it would be possible to reduce the number of examinations performed by 30% yet still detect 98% of serious disease. If confirmed in further prospective studies, this scoring system (or a modification) could more accurately assess individual priority for endoscopy and enable optimum use to be made of limited resources.


Two-incision total hip replacement: Intra-operative fluoroscopy versus imageless navigation for cup placement.
The purpose of this study was to describe the surgical technique and to investigate results of a modified two-incision total hip replacement using either intraoperative fluoroscopy or imageless navigation. Twenty-nine patients (30 hips) with a minimum follow-up of one year were enrolled in this study. The patients were evaluated at 3, 6, 12 weeks, 6 months, and 1-year. The functional recovery as represented by the Harris hip score and WOMAC scale were better in the fluoroscopy group of patients at the early postoperative stage (3 wks). Thereafter, both groups showed rapid recovery with no difference in scores. Injury to the lateral femoral cutaneous nerve was the most commonly seen complication and it occurred in 6 hips (fluoroscopy 2; imageless 4). The symptoms were transient and resolved in 6 months in all 6 cases. This study demonstrated that the role of intraoperative fluoroscopy could safely be replaced by an imageless navigation system for the MIS-2 THA.


Fibroblasts promote the formation of a continuous basal lamina during myogenesis in vitro.
Analyses were made of the requirements for the formation of a continuous basal lamina during myogenesis of quail muscle in vitro. A culture system was developed in which mass cultures of differentiating muscle cells were embedded in a native gel of rat tail collagen. Fibroblastic cells, which were also present in the cultures, migrated into the gel and within a few days surrounded the newly formed myotubes. In this environment, a continuous basal lamina was formed at the surface of the myotubes as demonstrated by immunofluorescent staining with monoclonal antibodies against type IV collagen, laminin, and heparan sulfate, as well as by electron microscopic immunolocalization. To distinguish between the role of the fibroblasts and the collagen gel in promoting basal lamina formation, clones of quail muscle cells lacking fibroblasts were subsequently embedded in a native rat tail collagen gel. Under these conditions, only very limited fluorescent staining for basement membrane components was observed associated with the myotubes. However, the introduction of chick muscle or skin fibroblasts into the clonal cultures just before gel formation resulted in the formation of an extensive basal lamina on the surface of the myotubes. Conditioned medium from fibroblast cultures by itself was not effective in promoting basal lamina formation. These results clearly show that during myogenesis in vitro fibroblasts must be in close proximity to the myotubes for a continuous basal lamina to form. These results probably relate closely to the interactions that must occur during myogenesis in vivo between the muscle cells and the surrounding connective tissue including the developing tendons.


Polysaccharide intercellular adhesin in biofilm: structural and regulatory aspects.
Staphylococcus aureus and Staphylococcus epidermidis are the leading etiologic agents of implant-related infections. Biofilm formation is the main pathogenetic mechanism leading to the chronicity and irreducibility of infections. The extracellular polymeric substances of staphylococcal biofilms are the polysaccharide intercellular adhesin (PIA), extracellular-DNA, proteins, and amyloid fibrils. PIA is a poly-β(1-6)-N-acetylglucosamine (PNAG), partially deacetylated, positively charged, whose synthesis is mediated by the icaADBC locus. DNA sequences homologous to ica locus are present in many coagulase-negative staphylococcal species, among which S. lugdunensis, however, produces a biofilm prevalently consisting of proteins. The product of icaA is an N-acetylglucosaminyltransferase that synthetizes PIA oligomers from UDP-N-acetylglucosamine. The product of icaD gives optimal efficiency to IcaA. The product of icaC is involved in the externalization of the nascent polysaccharide. The product of icaB is an N-deacetylase responsible for the partial deacetylation of PIA. The expression of ica locus is affected by environmental conditions. In S. aureus and S. epidermidis ica-independent alternative mechanisms of biofilm production have been described. S. epidermidis and S. aureus undergo to a phase variation for the biofilm production that has been ascribed, in turn, to the transposition of an insertion sequence in the icaC gene or to the expansion/contraction of a tandem repeat naturally harbored within icaC. A role is played by the quorum sensing system, which negatively regulates biofilm formation, favoring the dispersal phase that disseminates bacteria to new infection sites. Interfering with the QS system is a much debated strategy to combat biofilm-related infections. In the search of vaccines against staphylococcal infections deacetylated PNAG retained on the surface of S. aureus favors opsonophagocytosis and is a potential candidate for immune-protection.


Evaluation of Seroconversion Rate Following SARS COV 2 Vaccination in Health Care Workers at Shahid Beheshti University of Medical Sciences.
Vaccines are the most effective way to prevent Coronavirus 2 severe acute respiratory syndrome (SARS-CoV-2). This study examines and compares the efficiency of AstraZeneca, Sinopharm, and Sputnik vaccines and the correlation of antibody response with age, sex, and history of corona disease in employees of Shahid Beheshti University of Medical Sciences. 202 participants were included, of which 82 were administered the Astra-Zeneca, 59 were given the Sinopharm, and 61 were given the Sputnik vaccine. SARSCoV-2 IgM and IgG antibody levels were checked four weeks after passing the second dose of all three vaccines using the enzyme-linked immunosorbent assay (ELISA) technique. There was no significant difference between the amount of IgM and IgG antibodies among three vaccines (p=0.056). For all three vaccines, gender and age did not significantly affect the amount of IgM and IgG antibodies. The history of infection with COVID-19 increased the antibody response (p>0.5). The titer of IgM and IgG antibodies were not statistically significantly different. The IgM and IgG antibodies produced by vector-based vaccines are higher than the Sinopharm vaccine. Gender did not affect the produced antibody titer. No significant linear relationship was found between age and antibody titer. In people from this study who received two doses of the AstraZeneca vaccine and had a corona history, the average amount of both IgM and IgG antibodies was measured more than the other participants.


Factors associated with better survival after surgery in metastatic breast cancer patients.
Women with Metastatic Breast Cancer (MBC) and an intact primary have long been treated with systemic therapy alone. Local therapy is not considered unless for palliative reasons. However, several studies have suggested local treatment in the form of Surgery for the primary improves overall survival in certain groups of MBC patients. We evaluated the factors influencing the outcome in this group of patients. In a retrospective review of our prospective database, we identified the patients who presented with MBC and underwent surgery for primary tumour (2004-2009). Patients' surgical details and clinicopathological factors were reviewed. The overall survival of the MBC patients who underwent surgery was evaluated and compared depending on the various clinicopathological factors. Out of 196 patients with MBC, 48 underwent surgery of the primary tumor during their treatment course. Median overall survival was better in patients with young age (<=40 years), Estrogen receptor(ER) positive tumors (31.4 months vs 21.2 months), single metastatic site vs multiple metastatic sites (43.4 months vs 26.69 months). We also found that patients with low level of suspicion for metastases fared better than those with high level of suspicion (43.4 months vs 20.9 months). Our data analysis suggested that for MBC patients who undergo surgery, survival is significantly worse in patients with pathological T4 lesions and there is a trend towards better survival in younger patients and in those who have ER positive tumour, Her2neu negative tumour, single site of metastases and patients with low level of metastatic suspicion. However these factors need to be evaluated in a randomized trial comparing with patients who have not undergone surgery.


Endogenous myeloperoxidase is a mediator of joint inflammation and damage in experimental arthritis.
Myeloperoxidase (MPO) is implicated as a local mediator of tissue damage when released extracellularly in many chronic inflammatory diseases. The purpose of this study was to explore the role of endogenous MPO in experimental rheumatoid arthritis (RA). K/BxN serum-transfer arthritis was induced in C57BL/6 wild-type (WT) and MPO knockout (MPO(-/-) ) mice, and disease development was assessed. MPO activity was measured in joint tissues from mice with or without K/BxN arthritis. Collagen-induced arthritis (CIA) was induced in WT and MPO(-/-) mice, and disease development and immune responses were examined. MPO expression was assessed in synovial biopsy samples from patients with active RA, and the effect of MPO on synovial fibroblasts was tested in vitro. MPO was up-regulated in the joints of mice with K/BxN arthritis, and MPO deficiency attenuated the severity of the disease without affecting circulating cytokine levels. In CIA, MPO(-/-) mice had enhanced CD4+ T cell responses and reduced frequency of regulatory T cells in the lymph nodes and spleen, as well as augmented interleukin-17A and diminished interferon-γ secretion by collagen-stimulated splenocytes, without an effect on circulating anticollagen antibody levels. Despite enhanced adaptive immunity in secondary lymphoid organs, CIA development was attenuated in MPO(-/-) mice. Intracellular and extracellular MPO was detected in the synovium of patients with active RA, and human MPO enhanced the proliferation and decreased the apoptosis of synovial fibroblasts in vitro. MPO contributes to the development of arthritis despite suppressing adaptive immunity in secondary lymphoid organs. This suggests distinct effects of local MPO on arthritogenic effector responses.


Study protocol: determinants of participation and quality of life of adolescents with cerebral palsy: a longitudinal study (SPARCLE2).
Children and adults with impairments such as cerebral palsy have lower participation in life situations than able-bodied people. Less is known about their subjective perception of their lives, called their quality of life.During adolescence, rapid physical and psychological changes occur; although these may be more difficult for disabled than for able-bodied adolescents, little research has examined the lives of disabled adolescents.In 2003-4 a European Union funded project, SPARCLE, visited 818 children aged 8-12 years with cerebral palsy, sampled from population-based registers in nine European regions. The quality of life reported by these disabled children was similar to that of the general population but their participation was lower; levels of participation varied between countries even for children with similar severity of cerebral palsy.We are currently following up these children, now aged 13-17 years, to identify (i) to what extent contemporaneous factors (pain, impairment, psychological health and parental stress) predict their participation and quality of life, (ii) what factors modify how participation and quality of life at age 8-12 years are associated with participation and quality of life in adolescence, and (iii) whether differences between European countries in participation and quality of life can be explained by variations in environmental factors. Trained researchers will visit families to administer questionnaires to capture the adolescents' type and severity of impairment, socio-demographic characteristics, participation, quality of life, psychological health, pain, environmental access and parental stress. We will use multivariable models (linear, logistic or ordinal) to assess how adolescent participation, quality of life, psychological health, pain, environmental access and parental stress, vary with impairment and socio-demographic characteristics and, where possible, how these outcomes compare with general population data. For participation and quality of life, longitudinal analyses will assess to what extent these are predicted by corresponding levels in childhood and what factors modify this relationship. Structural equation modelling will be used to identify indirect relationships mediated by other factors.


[Crispr-Cas9 Gene Editing Revolution and the Its Ethical and Legal Challenges].
After discovering the CRISPR-Cas9 as an extraordinary method for Gene editing it is necessary to reflect on the ethical, political and legal impact of this technology. This work pretends to offer a preliminary consideration of these problems. I do not pay attention to the potential of CRISPR-Cas9 in the fields of health or environment, nor to all the ethical, legal and political challenges it involves. I principally focus the attention on the possibility of using CRISPR-Cas9 to alter the human germ line. There are some rulings on this topic delivered by intergovernmental organizations. There also are some statements from the scientific community on the matter. They are important in order to know the reasons why they propose a moratorium on the use of CRISPR-Cas9 for human germ line editing. I begin the paper with a short explanation on how CRISPR-Cas9 works.


Allogeneic Transplantation in Chronic Myeloid Leukemia and the Effect of Tyrosine Kinase Inhibitors on Survival: A Quasi-Experimental Study.
Tyrosine kinase inhibitors (TKIs) have changed the indications for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myeloid leukemia (CML). Therefore, we aimed to evaluate the effect of TKIs on allo-HSCT in CML. In this quasi-experimental study, we compared patient, disease, and transplantation characteristics as well as allo-HSCT outcomes between the pre-TKI era (before 2002) and the post-TKI era (2002 and later) in patients with CML. A total of 193 allo-HSCTs were performed between 1989 and 2012. Patients in the post-TKI era had more advanced disease (>chronic phase 1) at the time of transplant and more frequently received reduced-intensity conditioning compared to patients in the pre-TKI era. Relapse/progression occurred more frequently in the year ≥2002 group than in the year <2002 group (48% vs. 32% at 5 years, p=0.01); however, overall survival (OS) was similar in these two groups (5-year survival was 50.8% vs. 59.5%, respectively; p=0.3). TKIs (with donor lymphocyte infusions or alone) for treatment of relapse after allo-HSCT were available in the post-TKI era and were associated with improved OS. While the rates of hematologic remission at 3 months after allo-HSCT were similar between TKI eras, patients having remission had better disease-free survival (DFS) [relative risk (RR): 0.15, confidence interval (CI) 95%: 0.09-0.24, p<0.001] and OS (RR: 0.14, CI 95%: 0.09-0.23, p<0.001). Male allo-HSCT recipients had worse DFS (RR: 1.7, CI 95%: 1.2-2.5, p=0.007) and OS (RR: 1.7, CI 95%: 1.1-2.6, p=0.02) than females. TKIs are an effective option for the treatment of relapse after allo-HSCT in CML. Hematologic remission after allo-HSCT is also an important factor for survival in CML patients.


A comparison of extraperitoneal and intraperitoneal approaches for robotic prostatectomy.
This study compared oncologic and health-related quality-of-life outcomes among patients undergoing intraperitoneal or extraperitoneal robotic prostatectomy. Of 215 patients undergoing robotic prostatectomy, the approach was intraperitoneal in 48 and extraperitoneal in 167. Cancer control was evaluated using margin status. Recovery after surgery and functional health was assessed using the convalescence and recovery evaluation and expanded prostate cancer index composite questionnaires, respectively. Positive surgical margin rates were similar between approaches (14% extraperitoneal, 10% intraperitoneal; P = .63). Functional outcomes were slightly improved for those with the extraperitoneal approach (i.e., higher urinary irritation/obstruction scores at 3 months). The extraperitoneal group demonstrated higher activity (91.8 vs 83.3, P = .03) and cognitive scores (94.9 vs. 91.7, P = .04) at 6 weeks as well as higher gastrointestinal scores at 2 weeks (94.2 vs. 90.8, P = .05). These data support efforts to broaden the adoption of the extraperitoneal approach for robotic prostatectomy.


Orthopedic Surgery and Anesthesiology Surgical Improvement Strategies Project: Phase I Outcomes.
This study aimed to improve institutional value-based patient care processes, provider collaboration, and continuous process improvement mechanisms for primary total hip arthroplasties and total knee arthroplasties through establishment of a perioperative orthopedic surgical home. On June 1, 2017, an institutionally sponsored initiative commenced known as the orthopedic surgery and anesthesiology surgical improvement strategy project. A multidisciplinary team consisting of orthopedic surgeons, anesthesiologists, advanced practice providers, nurses, pharmacists, physical therapists, social workers, and hospital administration met regularly to identify areas for improvement in the preoperative, intraoperative, and post-anesthesia care unit, and postoperative phases of care. Mean hospital length of stay decreased from 2.7 to 2.2 days (P < .001), incidence of discharge to a skilled nursing facility decreased from 24% to 17% (P = .008), and the number of patients receiving physical therapy on the day of surgery increased from 10% to 100% (P < .001). Press-Ganey scores increased from 74.9 to 75.8 (94th percentile), while mean and maximum pain scores, opioid consumption, and hospital readmission rates remained unchanged (lowest P = .29). Annual total hip arthroplasty and total knee arthroplasty surgical volume increased by 11.4%. Decreased hospital length of stay and increased surgical volume yielded a combined annual savings of $2.5 million across the 9 involved orthopedic surgeons. Through application of perioperative surgical home tools and concepts, key advances included phase of care integration, enhanced data management, decreased length of stay, coordinated perioperative management, increased surgical volume without personnel additions, and more efficient communication and patient care flow across preoperative, intraoperative, and postoperative phases. III Therapeutic.


Uterine massage for preventing postpartum haemorrhage.
Postpartum haemorrhage (PPH) (bleeding from the genital tract after childbirth) is a major cause of maternal mortality and disability, particularly in under-resourced areas. In these settings, uterotonics are often not accessible. There is a need for simple, inexpensive techniques which can be applied in low-resourced settings to prevent and treat PPH. Uterine massage is recommended as part of the routine active management of the third stage of labour. However, it is not known whether it is effective. If shown to be effective, uterine massage would represent a simple intervention with the potential to have a major effect on PPH and maternal mortality in under-resourced settings. To determine the effectiveness of uterine massage after birth and before or after delivery of the placenta, or both, to reduce postpartum blood loss and associated morbidity and mortality. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013). All published, unpublished and ongoing randomised controlled trials comparing uterine massage alone or in addition to uterotonics before or after delivery of the placenta, or both, with non-massage. Two researchers independently considered trials for eligibility, assessed risk of bias and extracted the data using the agreed form. Data were checked for accuracy. The effect of uterine massage commenced before or after placental delivery were first assessed separately, and then the combined for an overall result. This review included two randomised controlled trials. The first trial included 200 women who were randomised to receive uterine massage or no massage following delivery of the placenta, after active management of the third stage of labour including use of oxytocin. The numbers of women with blood loss more than 500 mL was small, with no statistically significant difference (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.16 to 1.67). There were no cases of retained placenta in either group. The mean blood loss was significantly less in the uterine massage group at 30 minutes (mean difference (MD) -41.60 mL, 95% CI -75.16 to -8.04) and 60 minutes after trial entry (MD -77.40 mL, 95% CI -118.71 to -36.09). The need for additional uterotonics was significantly reduced in the uterine massage group (RR 0.20, 95% CI 0.08 to 0.50).For use of uterine massage before and after delivery of the placenta, one trial recruited 1964 women in Egypt and South Africa. Women were assigned to receive oxytocin, uterine massage or both after delivery of the baby but before delivery of the placenta. There was no added benefit for uterine massage plus oxytocin over oxytocin alone as regards blood loss greater than or equal to 500 mL (average RR 1.56, 95% CI 0.44, 5.49; random-effects) or need for additional use of uterotonics (RR 1.02, 95% CI 0.56 to 1.85).The two trials were combined to examine the effect of uterine massage commenced either before or after delivery of the placenta. There was substantial heterogeneity with respect to the blood loss 500 mL or more after trial entry. The average effect using a random-effects model found no statistically significant differences between groups (average RR 1.14, 95% CI 0.39 to 3.32; random-effects). The results of this review are inconclusive, and should not be interpreted as a reason to change current practice. Due to the limitations of the included trials, more trials with sufficient numbers of women are needed in order to estimate the effects of sustained uterine massage. All the women compared in this review received oxytocin as part of the active management of labour. Recent research suggests that once an oxytocic has been given, there is limited scope for further reduction in postpartum blood loss. Trials of uterine massage in settings where uterotonics are not available, and which measure women's experience of the procedure, are needed.


Gimatecan, a novel camptothecin with a promising preclinical profile.
The realization that position 7 of camptothecin allows several options in chemical manipulation of the drug has stimulated a systematic investigation of a variety of substituents in this position. These efforts resulted in the identification of a novel series of 7-oxyiminomethyl derivatives. Among compounds of this series we have selected a promising lipophilic derivative, gimatecan, for further development. The relevant features of gimatecan are: (i) marked cytotoxic potency, likely related to multiple factors, including a potent inhibition of topoisomerase I, a persistent stabilization of the cleavable complex, an increased intracellular accumulation and a peculiar subcellular localization; (ii) lack of recognition by known resistance-related transport systems; (iii) increased lactone stability and favorable pharmacokinetics; (iv) good oral bioavailability; and (v) an impressive antitumor efficacy in a large panel of human tumor xenografts, with various treatment schedules. Phase I clinical studies with oral administration support the preclinical results of the novel camptothecin. Using different schedules and dosing durations, gimatecan exhibited an acceptable toxicity profile, with myelotoxicity being the dose-limiting toxic effect. An appreciable number of tumor responses was achieved and favorable pharmacokinetics with a very long terminal half-life was observed. The clinical development of gimatecan is currently ongoing, with phase II studies in diverse tumor types (colon, lung, breast carcinoma and pediatric tumors).


An Evaluation of Expedited Transcription Methods for School-Age Children's Narrative Language: Automatic Speech Recognition and Real-Time Transcription.
Purpose This study examined the accuracy and potential clinical utility of two expedited transcription methods for narrative language samples elicited from school-age children (7;5-11;10 [years;months]) with developmental language disorder. Transcription methods included real-time transcription produced by speech-language pathologists (SLPs) and trained transcribers (TTs) as well as Google Cloud Speech automatic speech recognition. Method The accuracy of each transcription method was evaluated against a gold-standard reference corpus. Clinical utility was examined by determining the reliability of scores calculated from the transcripts produced by each method on several language sample analysis (LSA) measures. Participants included seven certified SLPs and seven TTs. Each participant was asked to produce a set of six transcripts in real time, out of a total 42 language samples. The same 42 samples were transcribed using Google Cloud Speech. Transcription accuracy was evaluated through word error rate. Reliability of LSA scores was determined using correlation analysis. Results Results indicated that Google Cloud Speech was significantly more accurate than real-time transcription in transcribing narrative samples and was not impacted by speech rate of the narrator. In contrast, SLP and TT transcription accuracy decreased as a function of increasing speech rate. LSA metrics generated from Google Cloud Speech transcripts were also more reliably calculated. Conclusions Automatic speech recognition showed greater accuracy and clinical utility as an expedited transcription method than real-time transcription. Though there is room for improvement in the accuracy of speech recognition for the purpose of clinical transcription, it produced highly reliable scores on several commonly used LSA metrics. Supplemental Material https://doi.org/10.23641/asha.15167355.


Roux-en-Y reconstruction with stapled distal jejunal pouch after total gastrectomy.
Roux-en-Y reconstruction after total gastrectomy is a simple and safe procedure; however, it eliminates the gastric reservoir function and markedly changes the postoperative digestive physiology. The patients therefore suffer from insufficient food intake and malabsorption. It has been reported that jejunal pouch reconstruction increases food intake and improves the nutritional status. We established a novel Roux-en-Y reconstruction with stapled distal jejunal pouch after total gastrectomy. A jejunal pouch, 8 cm in size, was attached at the jejunojejunostomy. We performed this novel reconstruction for 20 gastric cancer patients after total gastrectomy with lymph node dissection as a feasible study. One year after operation, the average percentage weight was maintained in more than 90 per cent and 17 (85%) of these patients were in the normal range of the body mass index. This procedure may improve postoperative malnutrition after total gastrectomy according to our feasible study. A multicenter randomized trial of this approach comparing with Roux-en-Y reconstruction without a pouch is ongoing.


Speech errors of amnesic H.M.: unlike everyday slips-of-the-tongue.
Three language production studies indicate that amnesic H.M. produces speech errors unlike everyday slips-of-the-tongue. Study 1 was a naturalistic task: H.M. and six controls closely matched for age, education, background and IQ described what makes captioned cartoons funny. Nine judges rated the descriptions blind to speaker identity and gave reliably more negative ratings for coherence, vagueness, comprehensibility, grammaticality, and adequacy of humor-description for H.M. than the controls. Study 2 examined "major errors", a novel type of speech error that is uncorrected and reduces the coherence, grammaticality, accuracy and/or comprehensibility of an utterance. The results indicated that H.M. produced seven types of major errors reliably more often than controls: substitutions, omissions, additions, transpositions, reading errors, free associations, and accuracy errors. These results contradict recent claims that H.M. retains unconscious or implicit language abilities and produces spoken discourse that is "sophisticated," "intact" and "without major errors." Study 3 examined whether three classical types of errors (omissions, additions, and substitutions of words and phrases) differed for H.M. versus controls in basic nature and relative frequency by error type. The results indicated that omissions, and especially multi-word omissions, were relatively more common for H.M. than the controls; and substitutions violated the syntactic class regularity (whereby, e.g., nouns substitute with nouns but not verbs) relatively more often for H.M. than the controls. These results suggest that H.M.'s medial temporal lobe damage impaired his ability to rapidly form new connections between units in the cortex, a process necessary to form complete and coherent internal representations for novel sentence-level plans. In short, different brain mechanisms underlie H.M.'s major errors (which reflect incomplete and incoherent sentence-level plans) versus everyday slips-of-the tongue (which reflect errors in activating pre-planned units in fully intact sentence-level plans). Implications of the results of Studies 1-3 are discussed for systems theory, binding theory and relational memory theories.


Cloning and manipulation of the Escherichia coli cyclopropane fatty acid synthase gene: physiological aspects of enzyme overproduction.
Like many other eubacteria, cultures of Escherichia coli accumulate cyclopropane fatty acids (CFAs) at a well-defined stage of growth, due to the action of the cytoplasmic enzyme CFA synthase. We report the isolation of the putative structural gene, cfa, for this enzyme on an E. coli-ColE1 chimeric plasmid by the use of an autoradiographic colony screening technique. When introduced into a variety of E. coli strains, this plasmid, pLC18-11, induced corresponding increases in CFA content and CFA synthase activity. Subsequent manipulation of the cfa locus, facilitated by the insertion of pLC18-11 into a bacteriophage lambda vector, allowed genetic and physiological studies of CFA synthase in E. coli. Overproduction of this enzyme via multicopy cfa plasmids caused abnormally high levels of CFA in membrane phospholipid but no discernable growth perturbation. Infection with phage lambda derivatives bearing cfa caused transient overproduction of the enzyme, although pL-mediated expression of cfa could not be demonstrated in plasmids derived from such phages. CFA synthase specific activities could be raised to very high levels by using cfa runaway-replication plasmids. A variety of physiological factors were found to modulate the levels of CFA synthase in normal and gene-amplified cultures. These studies argue against several possible mechanisms for the temporal regulation of CFA formation.


Enrichment of native plastic-associated biofilm communities to enhance polyester degrading activity.
Plastic pollution is an increasing worldwide problem urgently requiring a solution. While recycling rates are increasing globally, only 9% of all plastic waste has been recycled, and with the cost and limited downstream uses of recycled plastic, an alternative is needed. Here, we found that expanded polystyrene (EPS) promoted high levels of bacterial biofilm formation and sought out environmental EPS waste to characterize these native communities. We demonstrated that the EPS attached communities had limited plastic degrading activity. We then performed a long-term enrichment experiment where we placed a robust selection pressure on these communities by limiting carbon availability such that the waste plastic was the only carbon source. Seven of the resulting enriched bacterial communities had increased plastic degrading activity compared to the starting bacterial communities. Pseudomonas stutzeri was predominantly identified in six of the seven enriched communities as the strongest polyester degrader. Sequencing of one isolate of P. stutzeri revealed two putative polyesterases and one putative MHETase. This indicates that waste plastic-associated biofilms are a source for bacteria that have plastic-degrading potential, and that this potential can be unlocked through selective pressure and further in vitro enrichment experiments, resulting in biodegradative communities that are better than nature.


Determinants of Left Ventricular Characteristics Assessed by Cardiac Magnetic Resonance Imaging and Cardiovascular Biomarkers Related to Kidney Transplantation.
Cardiac magnetic resonance (CMR) imaging accurately and precisely measures left ventricular (LV) mass and function. Identifying mechanisms by which LV mass change and functional improvement occur in some end-stage kidney disease (ESKD) patients may help to appropriately target kidney transplant (KT) recipients for further investigation and intervention. The concentration of serum adiponectin, a cardiovascular biomarker, increases in cardiac failure, its production being enhanced by B-type natriuretic peptide (BNP), and both serum adiponectin and BNP concentrations decline posttransplantation. We tested the hypothesis that kidney transplantation alters LV characteristics that relate to serum adiponectin concentrations. Prospective and observational cohort study. The study was performed at 3 adult kidney transplant and dialysis centers in Ontario, Canada. A total of 82 KT candidate subjects were recruited (39 to the KT group and 43 to the dialysis group). Predialysis patients were excluded. Subjects underwent CMR with a 1.5-tesla whole-body magnetic resonance scanner using a phased-array cardiac coil and retrospective vectorographic gating. LV mass, LV ejection fraction (LVEF), LV end-systolic volume (LVESV), and LV end-diastolic volume (LVEDV) were measured by CMR pre-KT and again 12 months post-KT (N = 39), or 12 months later if still receiving dialysis (N = 43). LV mass, LVESV, and LVEDV were indexed for height (m2.7) to calculate left ventricular mass index (LVMI), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI), respectively. Serum total adiponectin and N-terminal proBNP (NT-proBNP) concentrations were measured at baseline, 3 months, and 12 months. We performed a prospective 1:1 observational study comparing KT candidates with ESKD either receiving a living donor organ (KT group) or waiting for a deceased donor organ (dialysis group). Left ventricular mass index change was -1.98 ± 5.5 and -0.36 ± 5.7 g/m2.7 for KT versus dialysis subjects (P = .44). Left ventricular mass change was associated with systolic blood pressure (SBP) (P = .0008) and average LV mass (P = .0001). Left ventricular ejection fraction did not improve (2.9 ± 6.6 vs 0.7 ± 4.9 %, P = .09), while LVESVI and LVEDVI decreased more post-KT than with continued dialysis (-3.36 ± 5.6 vs -0.22 ± 4.4 mL/m2.7, P < .01 and -4.9 ± 8.5 vs -0.3 ± 9.2 mL/m2.7, P = .02). Both adiponectin (-7.1 ± 11.3 vs -0.11 ± 7.9 µg/mL, P < .0001) and NT-proBNP (-3811 ± 8130 vs 1665 ± 20013 pg/mL, P < .0001) declined post-KT. Post-KT adiponectin correlated with NT-proBNP (P = .001), but not estimated glomerular filtration rate (eGFR) (P = .13). Change in adiponectin did not correlate with change in LVEF in the KT group (Spearman ρ = 0.16, P = .31) or dialysis group (Spearman ρ = 0.19, P = .21). Few biomarkers of cardiac function were measured to fully contextualize their role during changing kidney function. Limited intrapatient biomarker sampling and CMR measurements precluded constructing dose-response curves of biomarkers to LV mass and function. The CMR timing in relation to dialysis was not standardized. The LVESVI and LVEDVI but not LVMI or LVEF improve post-KT. LVMI and LVEF change is independent of renal function and adiponectin. As adiponectin correlates with NT-proBNP post-KT, improved renal function through KT restores the normal heart-endocrine axis.


Reversible and irreversible effects of nitric oxide on the soluble hydrogenase from Alcaligenes eutrophus H16.
The effects of NO on the H2-oxidizing and diaphorase activities of the soluble hydrogenase from Alcaligenes eutrophus H16 were investigated. With fully activated enzyme, NO (8-150 nM in solution) inhibited H2 oxidation in a time- and NO-concentration-dependent process. Neither H2 nor NAD+ appeared to protect the enzyme against the inhibition. Loss of activity in the absence of an electron acceptor was about 10 times slower than under turnover conditions. The inhibition was partially reversible; approx. 50% of full activity was recoverable after removal of the NO. Recovery was slower in the absence of an electron acceptor than in the presence of H2 plus an electron acceptor. The diaphorase activity of the unactivated hydrogenase was not affected by NO concentrations of up to 200 microM in solution. Exposure of the unactivated hydrogenase to NO irreversibly inhibited the ability of the enzyme to be fully activated for H2-oxidizing activity. The enzyme also lost its ability to respond to H2 during activation in the presence of NADH. The results are interpreted in terms of a complex inhibition that displays elements of (1) a reversible slow-binding inhibition of H2-oxidizing activity, (2) an irreversible effect on H2-oxidizing activity and (30 an irreversible inhibition of a regulatory component of the enzyme. Possible sites of action for NO are discussed.


The Correlations of Human Atrial Natriuretic Peptide on Cardiac Function and Hemodynamics in Pediatric Septic Shock.
We aimed to determine the correlations of human Atrial Natriuretic Peptide (ANP) on cardiac function and hemodynamics in pediatric septic shock. We conducted an observational and prospective study on 30 children with septic shock. Measurement of the level of human atrial natriuretic peptide was determined in the serum of patients. Cardiac power (CP) is a cardiac function parameter measured with cardiac output (cardiovascular flow) and mean arterial (intravascular) pressure. Cardiac output and mean arterial pressure were monitored using pressure recording analytical methods (PRAM). Hemodynamic status was represented by a vasoactive inotropic score. Thirty pediatric septic shock patients fulfilled the eligibility criteria. The human ANP level was not significantly different in pediatric septic shock on three days of examination. Cardiac power was significantly different in pediatric septic shock on three days of examination. There was a correlation between human ANP and cardiac power on day 3 and human ANP and VIS on day 2. There was a significant correlation between human ANP level and cardiac power on day 3 and ANP level and VIS on day 2. The cardiac power on day 3 and VIS on 48 hours can be alternatives to evaluate the hemodynamic status and cardiac function concerning human ANP in pediatric septic shock.


Genome Stability by DNA Polymerase β in Neural Progenitors Contributes to Neuronal Differentiation in Cortical Development.
DNA repair is crucial for genome stability in the developing cortex, as somatic de novo mutations cause neurological disorders. However, how DNA repair contributes to neuronal development is largely unknown. To address this issue, we studied the spatiotemporal roles of DNA polymerase β (Polβ), a key enzyme in DNA base excision repair pathway, in the developing cortex using distinct forebrain-specific conditional knock-out mice, Emx1-Cre/Polβ fl/fl and Nex-Cre/Polβ fl/fl mice. Polβ expression was absent in both neural progenitors and postmitotic neurons in Emx1-Cre/Polβ fl/fl mice, whereas only postmitotic neurons lacked Polβ expression in Nex-Cre/Polβ fl/fl mice. We found that DNA double-strand breaks (DSBs) were frequently detected during replication in cortical progenitors of Emx1-Cre/Polβ fl/fl mice. Increased DSBs remained in postmitotic cells, which resulted in p53-mediated neuronal apoptosis. This neuronal apoptosis caused thinning of the cortical plate, although laminar structure was normal. In addition, accumulated DSBs also affected growth of corticofugal axons but not commissural axons. These phenotypes were not observed in Nex-Cre/Polβ fl/fl mice. Moreover, cultured Polβ-deficient neural progenitors exhibited higher sensitivity to the base-damaging agent methylmethanesulfonate, resulting in enhanced DSB formation. Similar damage was found by vitamin C treatment, which induces TET1-mediated DNA demethylation via 5-hydroxymethylcytosine. Together, genome stability mediated by Polβ-dependent base excision repair is crucial for the competence of neural progenitors, thereby contributing to neuronal differentiation in cortical development.SIGNIFICANCE STATEMENT DNA repair is crucial for development of the nervous system. However, how DNA polymerase β (Polβ)-dependent DNA base excision repair pathway contributes to the process is still unknown. We found that loss of Polβ in cortical progenitors rather than postmitotic neurons led to catastrophic DNA double-strand breaks (DSBs) during replication and p53-mediated neuronal apoptosis, which resulted in thinning of the cortical plate. The DSBs also affected corticofugal axon growth in surviving neurons. Moreover, induction of base damage and DNA demethylation intermediates in the genome increased DSBs in cultured Polβ-deficient neural progenitors. Thus, genome stability by Polβ-dependent base excision repair in neural progenitors is required for the viability and differentiation of daughter neurons in the developing nervous system.


Rectal gunshot wounds. Management of civilian injuries.
The diagnosis and operative management of 43 consecutive low velocity wounds of the rectum were evaluated with regard to postoperative morbidity and mortality. Rectal and proctoscopic examinations, although frequently positive (80% and 91%, respectively), were not uniformly reliable in making the preoperative diagnosis. Diversion of the fecal stream by colostomy occupies a key role in operative management. Loop colostomy appears not only as efficacious as end colostomy and mucus fistula, but also requires less time to perform and subsequently close. Distal rectal washout is an important adjunct which reduces the incidence of rectal and intra-abdominal infectious complications. Civilian and military wounds of the rectum appear to differ in terms of the postoperative complications, mortality rate, and management techniques.


[The peculiarities of stability of vertical posture in patients with segmental lesions of the spinal cord].
Using computer stabilography, vertical posture has been studied in 3 groups of children and adolescences with traumatic lesion of the spinal cord after surgery of congenital myelocele (n=10) and myelodysplasia (n=10) and in 124 healthy controls. Also, an extent of segmental lesions was investigated by electroneuromyography of lower extremities muscles. Patients with pronounced segmental lesion had small-amplitude, -velocity and -frequency variations of body center of gravity (BCG) during standing with visual control. After excluding visual control of vertical posture, there was a significant decrease of vertical stability that suggests a relevant role of visual analyzer in the control of vertical posture. In patients with minor segmental lesion, BCG variations of small amplitude, velocity and frequency were observed. Exclusion of visual control did not result in significant reduction of vertical stability. It is concluded that stabilographic survey is an objective method for diagnosis of an extent of segmental lesion of the spinal cord.


Shigella flexneri remodeling and consumption of host lipids during infection.
Bacterial pathogens have vastly distinct sites that they inhabit during infection. This requires adaptation due to changes in nutrient availability and antimicrobial stress. The bacterial surface is a primary barrier, and here, we show that the bacterial pathogen Shigella flexneri increases its surface decorations when it transitions to an intracellular lifestyle. We also observed changes in bacterial and host cell fatty acid homeostasis. Specifically, intracellular S. flexneri increased the expression of their fatty acid degradation pathway, while the host cell lipid pool was significantly depleted. Importantly, bacterial proliferation could be inhibited by fatty acid supplementation of host cells, thereby providing novel insights into the possible link between human malnutrition and susceptibility to S. flexneri.


Strength training for children and adolescents.
The potential benefits of youth strength training extend beyond an increase in muscular strength and may include favorable changes in selected health- and fitness-related measures. If appropriate training guidelines are followed, regular participation in a youth strength-training program has the potential to increase bone mineral density, improve motor performance skills, enhance sports performance, and better prepare our young athletes for the demands of practice and competition. Despite earlier concerns regarding the safety and efficacy of youth strength training, current public health objectives now aim to increase the number of boys and girls age 6 and older who regularly participate in physical activities that enhance and maintain muscular fitness. Parents, teachers, coaches, and healthcare providers should realize that youth strength training is a specialized method of conditioning that can offer enormous benefit but at the same time can result in serious injury if established guidelines are not followed. With qualified instruction, competent supervision, and an appropriate progression of the volume and intensity of training, children and adolescents cannot only learn advanced strength training exercises but can feel good about their performances, and have fun. Additional clinical trails involving children and adolescents are needed to further explore the acute and chronic effects of strength training on a variety of anatomical, physiological, and psychological parameters.


Effect on Antimicrobial Resistance of a Policy Restricting Over-the-Counter Antimicrobial Sales in a Large Metropolitan Area, São Paulo, Brazil.
Although restricting over-the-counter (OTC) antimicrobial drug sales is recommended globally, no data track its effect on antimicrobial resistance (AMR) in bacteria. We evaluated the effect of a national policy restricting OTC antimicrobial sales, put in place in November 2010, on AMR in a metropolitan region of São Paulo, Brazil. We reviewed associations between antimicrobial sales from private pharmacies and AMR in 404,558 Escherichia coli and 5,797 Streptococcus pneumoniae isolates using a dynamic regression model based on a Bayesian approach. After policy implementation, a substantial drop in AMR in both bacterial species followed decreased amoxicillin and trimethoprim/sulfamethoxazole sales. Conversely, increased ciprofloxacin sales were associated with increased ciprofloxacin resistance, and extended spectrum β-lactamases-positive E. coli isolates and azithromycin sales increases after 2013 were associated with increased erythromycin resistance in S. pneumoniae isolates. These findings suggest that restricting OTC antimicrobial sales may influence patterns of AMR, but multifaceted approaches are needed to avoid unintended consequences.


Attitudes and perceptions of Dutch companion animal veterinarians towards antimicrobial use and antimicrobial resistance.
Antimicrobial use (AMU) in humans and animals facilitates the emergence of antimicrobial resistance (AMR). With increasing AMR being recognised as a major global threat for public health, responsible AMU is strongly advocated in both human and veterinary medicine. Knowledge on factors influencing antimicrobial prescribing behaviour of companion animal veterinarians is needed to promote responsible AMU in companion animals and to improve compliance with current legislation and guidelines. The present study aimed to quantitively investigate attitudes and perceptions of companion animal veterinarians towards AMU and AMR and to identify associations with demographic characteristics as possible explanatory variables. A self-administered questionnaire was developed based upon an earlier qualitative interview study, and 1608 potential participants (i.e. practising companion animal veterinarians) were invited. The questionnaire included questions addressing general descriptives of the respondents and questions with 6-point Likert scale statements, to assess attitudes towards AMU, AMR, factors influencing antimicrobial prescribing, and possible options to support responsible AMU. The response rate was 32% (22% when complete questionnaires considered). Categorical Principal Component Analysis (CATPCA) was conducted on 76 Likert scale questions. This resulted in a final model with 37 questions explaining 38.7% of the variance of the question scores, with three underlying dimensions ("attitudinal profiles"). Additionally, general descriptives were added to the CATPCA as possible explanatory variables. The first dimension, related to "social responsibility" was positively associated with veterinarians working in clinics dedicated to companion animals, with veterinarians working in a referral clinic, and with more experienced veterinarians. The second dimension was related to "scepticism", which was positively associated with being a male veterinarian and with more experienced veterinarians. The third dimension was related to "risk avoidance", especially regarding surgical procedures, and was negatively associated with veterinarians working in clinics in urban areas and with veterinarians working part-time. Antimicrobial prescribing behaviour was self-reported to be well considered, and respondents did not see economic drivers as important influencing factors. The unwillingness of owners and financial constraints were perceived as important barriers for performing further diagnostics. To improve AMU, a multifaceted approach, taking differences between companion animal veterinarians (e.g., in experience and gender) and differences in work situation (e.g., full-time versus part-time) into account, should be directed at companion animal veterinarians and owners. Moreover, a joint and comprehensive effort of several stakeholders, like veterinary nurses, guideline developers, pharmaceutical industry, and providers of diagnostics, is needed to optimise AMU in companion animals.