Molecular characterization and modular analysis of human MyD88.
MyD88 was first characterized as a myeloid differentiation primary response gene in mice, activated in M1 myeloleukemic cells following interleukin-6 (IL-6) induced growth arrest and terminal differentiation. Analysis of expressed sequence tags (ESTs) from activated dendritic cell libraries led to the indentification of cDNAs encoding the human homolog (hMyD88). The original description of MyD88 as a 243 aa protein may reflect a truncated mouse cDNA since the 2682 nt hMyD88 cDNA predicts a 296 aa cytoplasmic protein. Consistent with this proposal is the detection of a 33 kDa protein in human heart, kidney and liver tissue. The expression pattern of MyD88 is also more widespread than originally believed: a 2.6 kb hMyD88 mRNA species was found to be constitutively expressed in many adult human tissues; in addition MyD88 expression was observed in monocyte, T, B, NK and dendritic cells. The MyD88 protein has a modular structure composed of an N-terminal 'death domain' (DD) similar to the intracellular segments of TNF receptor 1 (TNFR1) and FAS and a C-terminal region related to the signaling domains of vertebrate interleukin-1 receptors (IL-1R) and the Drosophila morphogen Toll. This intriguing structural framework may endow MyD88 with unique signaling capabilities.


Characterisation of vancomycin-resistant enterococci from hospitalised patients at a tertiary centre over a seven-year period.
Vancomycin-resistant enterococci (VRE) were isolated from 41 patients at a medical centre in southern Taiwan from 1999 to 2005. This accounted for 0.55% of 7449 patients with clinical colonisation or infection due to Enterococcus species. Nine (22%) patients had clinical infections caused by VRE. Twenty-five (61%) VRE isolates were Enterococcus faecalis with VanA phenotype and vanA gene cluster, the remaining 16 (39%) isolates were Enterococcus faecium with VanB phenotype and vanB (15 isolates) or vanA (1 isolate) gene cluster. The esp gene cluster was found in 6 (24%) E. faecalis isolates and 14 (87.5%) E. faecium isolates, and hyl in 2 (8%) E. faecalis and 6 (37.5%) E. faecium isolates. Analysis of SmaI-digested DNA by pulsed-field gel electrophoresis revealed that most isolates of E. faecalis were distinct, indicating a limited person-to-person spread or sporadic nature of spread. By contrast, 10 (67%) of 15 VanB phenotype E. faecium isolates were identical, suggesting the presence of an occult and limited clonal spread at the hospital. The presence of the esp or hyl gene was not associated with the virulence or outbreak of VRE. In summary, epidemiological data and molecular typing suggest that there was occult clonal spread of VanB phenotype-vanB genotype E. faecium in the surgical ICU, and the limited person-to-person spread or sporadic nature of E. faecalis. Infection control measures are warranted due to the potential for spread of VRE.


Emerging roles of microRNAs in the control of embryonic stem cells and the generation of induced pluripotent stem cells.
MicroRNAs (miRNAs) have emerged as critical regulators of gene expression. These small, non-coding RNAs are believed to regulate more than a third of all protein coding genes, and they have been implicated in the control of virtually all biological processes, including the biology of stem cells. The essential roles of miRNAs in the control of pluripotent stem cells were clearly established by the finding that embryonic stem (ES) cells lacking proteins required for miRNA biogenesis exhibit defects in proliferation and differentiation. Subsequently, the function of numerous miRNAs has been shown to control the fate of ES cells and to directly influence critical gene regulatory networks controlled by pluripotency factors Sox2, Oct4, and Nanog. Moreover, a growing list of tissue-specific miRNAs, which are silenced or not processed fully in ES cells, has been found to promote differentiation upon their expression and proper processing. The importance of miRNAs for ES cells is further indicated by the exciting discovery that specific miRNA mimics or miRNA inhibitors promote the reprogramming of somatic cells into induced pluripotent stem (iPS) cells. Although some progress has been made during the past two years in our understanding of the contribution of specific miRNAs during reprogramming, further progress is needed since it is highly likely that miRNAs play even wider roles in the generation of iPS cells than currently appreciated. This review examines recent developments related to the roles of miRNAs in the biology of pluripotent stem cells. In addition, we posit that more than a dozen additional miRNAs are excellent candidates for influencing the generation of iPS cells as well as for providing new insights into the process of reprogramming.


Detection of epidermal growth factor receptor mRNA in peripheral blood: a new marker of circulating neoplastic cells in bladder cancer patients.
Despite the large number of studies performed in solid tumors, few attempts at molecular detection of urothelial cells in blood have been made. Specifically, only uroplakin II (UP-II) and cytokeratin 20 (CK-20) have been suggested as tumor markers in the blood of bladder cancer patients. Epidermal growth factor receptor (EGFR) mRNA expression was found in the blood of patients with some types of carcinoma; nevertheless, its expression has been never investigated in the blood of patients with urothelial tumors. We used a EGFR-based reverse transcription-PCR assay for the detection of tumoral cells in the blood of 27 patients with bladder cancer, in 30 healthy donors, and in 9 patients with cystitis. EGFR expression was compared with that of known markers of circulating epithelial cells, CK-19 and CK-20, and to a urothelial-specific marker, UP-II. Analysis by reverse transcription-PCR and Southern blot hybridization showed no evidence of EGFR and UP-II mRNA expression in any of the samples used as controls. Analysis of healthy donors showed mRNA expression for CK-19 and CK-20 in 6 of 30 and in 4 of 30 samples, respectively. All patients with cystitis resulted negative for EGFR expression, whereas 3 of 9, 2 of 9, and 3 of 9 were found expressing CK-19, CK-20, and UP-II, respectively. Among blood samples from tumoral patients, 74% had EGFR mRNA and 41% had positive signals for CK-19, whereas positivity for CK-20 and UP-II was found in 15% and 37% of patients, respectively. These results seem to indicate that EGFR mRNA in the blood may be a useful tumor marker in bladder cancer patients, as well as in other patients with epithelial tumors.


Aldosterone, from (patho)physiology to treatment in cardiovascular and renal damage.
Aldosterone, a steroid hormone with mineralocorticoid activity, is far more than merely a salt-and-water hormone. Aldosterone has a number of non-classical, mineralocorticoid receptor (MR)-mediated actions, including tissue remodeling, modulation of vascular tone and stimulating inflammation and fibrosis, which may fuel progression of end organ damage. Aldosterone breakthrough during blockade of the renin-angiotensin aldosterone system (RAAS) may explain why this treatment regimen only confers partial cardiovascular and renal protection. Of major interest, aldosterone is deleterious only if inappropriately high for its sodium status i.e. high aldosterone and high sodium. The mechanism of sodium dependence of aldosterone-induced renal and cardiovascular damage continues to fascinate. Aldosterone excess increases sodium and fluid retention and consequently increases blood pressure, which, in turn, mediates target organ damage. Moreover, blood pressure independent effects play a role with dissociation of low circulating and high tissue aldosterone levels during high sodium intake and possibly enhanced MR signaling. MR blockade is a valuable strategy, which has potency to halt the progressive end organ damage as observed during current treatments. In heart failure, MR blockade on top of RAAS blockade reduces hard clinical endpoints. Despite encouraging results on the intermediate endpoint proteinuria, long-term data on the efficacy and safety of MR blockade in preventing dialysis and/or cardiovascular endpoints in chronic kidney disease are still lacking. It is obligatory that future clinical studies on the effects of MR blockade on end-organ damage take into account the sodium status.


CyGate Provides a Robust Solution for Automatic Gating of Single Cell Cytometry Data.
To gain a better understanding of the complex human immune system, it is necessary to measure and interpret numerous cellular protein expressions at the single cell level. Mass cytometry is a relatively new technology that offers unprecedented information about the protein expression of a single cell. Conversely, the analysis of high-dimensional and multiparametric mass cytometric data sets presents a new computational challenge. For instance, conventional "manual gating" analysis was inefficient and unreliable for multiparametric phenotyping of the heterogeneous immune cellular system; consequently, automated methods have been developed to address the high dimensionality of mass cytometry data and enhance the reproducibility of the analysis. Here, we present CyGate, a semiautomated method for classifying single cells into their respective cell types. CyGate learns a gating strategy from a reference data set, trains a model for cell classification, and then automatically analyzes additional data sets using the trained model. CyGate also supports the machine learning framework for the classification of "ungated" cells, which are typically disregarded by automated methods. CyGate's utility was demonstrated by its high performance in cell type classification and the lowest generalization error on various public data sets when compared to the state-of-the-art semiautomated methods. Notably, CyGate had the shortest execution time, allowing it to scale with a growing number of samples. CyGate is available at https://github.com/seungjinna/cygate.


Effect on brainstem auditory evoked responses of posterior semicircular canal occlusion in guinea pigs.
The site of origin of benign paroxysmal positional vertigo is the posterior semicircular canal and when persistent, the condition is known as cupulolithiasis. Singular neurectomy is the current procedure of choice for the treatment of incapacitating cupulolithiasis. The neurectomy is difficult to learn and carries a significant risk of hearing loss. An alternative procedure, whereby the posterior canal is occluded, is discussed. This was performed on 11 guinea pigs and the effect on hearing was measured using brainstem evoked audiometry. Eight animals showed no hearing loss while the other three had a mild to moderate loss of hearing due to intra-operative complications. The effect of canal plugging on hearing compares favorably with the hearing results obtained with singular neurectomy. Posterior semicircular canal occlusion is suggested as a safer and technically easier treatment for incapacitating cupulolithiasis.


[Information modeling in the analysis of authors' abstracts of dissertations on radiotherapy].
The information simulating method was used to analyse 62 authors' abstracts of dissertations (14 of them were doctoral theses) in radiation therapy published over the last 8 years. The objects of radiation therapy were tumorous as well as nontumorous diseases (90 and 10% respectively). The problems of radiation therapy in G. I. T. pathology, particularly in esophageal and rectal cancer, were considered in 35% of the dissertations devoted to radiation therapy of cancer patients. A lot of dissertations were also concerned with the therapy of lung, cervical and breast cancer and Hodgkin's disease. The authors' attention was directed, in particular, to a study of intensive preoperative irradiation including that of G. I. T. and lung tumors. Most of the dissertations were concerned with the use of different types of gamma-therapy. Betatron therapy was employed to advantage for cervical and lung cancer. Some papers represented the results of randomized studies that undoubtedly raise the reliability of the obtained data. The correlation of the main trends in radiation therapy revealed by the information simulating methods with reviews over the recent years, provides an opportunity to recommend this method to research workers for the classification of literature sources and research design.


Noise-induced hearing loss in the contralateral ear during otologic and neurotologic surgeries.
Noise-induced hearing loss in the non-surgical ear during otologic/neurotologic surgery has not been well studied. The purpose of this study was to evaluate changes in hearing that may occur in the contralateral (i.e., non-surgical) ear after various otologic/neurotologic surgeries due to noise generated by drills. We hypothesized that otologic/neurotologic surgeries, longer in duration, would suggest longer drilling times and result in decreased hearing in the contralateral ear as evidenced by a change post-operative pure tone air conduction thresholds when compared to pre-operative thresholds. A retrospective chart review at a tertiary referral center. Adult patients (18-75 years old) who underwent otologic/neurotologic surgeries from May 1, 2016 through May 1, 2021 were considered for inclusion. Surgeries included vestibular schwannoma resection (translabyrinthine, middle cranial fossa, or retrosigmoid approaches), endolymphatic sac/shunt and labyrinthectomy for Meniere's disease, and tympanomastoid surgery for middle ear pathology (e.g., cholesteatoma). Patient characteristics obtained through record review included age, sex, surgical procedure, pre-operative and post-operative audiometric thresholds and word recognition scores (WRS) for the contralateral ear, and duration of surgery. No significant differences were observed for change in audiometric thresholds in the contralateral ear for any surgery when considering individual frequencies. Additionally, no significant change in WRS was observed for any surgical approach. The risk of hearing loss in the non-surgical ear during various otologic/neurotologic surgeries appears to be minimal when measured via routine clinical tests.


Saccade adaptation goes for the goal.
The oculomotor system maintains saccade accuracy by adjusting saccades that are consistently inaccurate. Four experiments were performed to determine the relative contribution of background and target postsaccadic displacement. Unlike typical saccade adaptation experiments, we used natural image scenes and masked target and background displacements during the saccade to exclude motion signals from allowing detection of the displacements. We found that the background had no effect on saccade gain while the target drove gain changes. Only when the target was blanked after the saccade did we observe some adaptation in the direction of the background displacement. We conclude that target selection is critical to saccade adaptation, and operates effectively against natural image backgrounds.


Condom awareness and intended use: gender and religious contrasts among school pupils in rural Masaka, Uganda.
A cross-sectional questionnaire survey examining knowledge, attitudes and intended use of condoms was conducted among 1,821 pupils (mean age = 14.2 years, range = 9--24) from 27 primary and secondary schools in rural south western Uganda. Condom education is not provided in Ugandan schools, but both boys and girls had relatively high overall levels of knowledge, even though boys demonstrated a higher level than girls. This suggests that respondents had successfully obtained reliable information from other sources. Boys and girls had similar and fairly positive attitudes towards condoms, although considerable shyness was expressed, both about discussing condoms with a partner and buying them. Fifty-eight per cent said that they themselves would use a condom if one were available, but girls were far less likely than boys to say so. Roman Catholics (46% of the sample) were less knowledgeable and less positive about condoms than non-Catholics, and the boys in this group, but not the girls, were also much less likely to say they would use one. Possible interventions based on these findings are discussed, and a research agenda for the delivery of assertiveness training to girls is proposed.


Vascular Reactivity to Hypercapnia Is Impaired in the Cerebral and Retinal Vasculature in the Acute Phase After Experimental Subarachnoid Hemorrhage.
Objective: Impaired cerebral blood flow (CBF) regulation, such as reduced reactivity to hypercapnia, contributes to the pathophysiology after aneurysmal subarachnoid hemorrhage (SAH), but temporal dynamics in the acute phase are unknown. Featuring comparable molecular regulation mechanisms, the retinal vessels participate in chronic and subacute stroke- and SAH-associated vessel alterations in patients and can be studied non-invasively. This study is aimed to characterize the temporal course of the cerebral and retinal vascular reactivity to hypercapnia in the acute phase after experimental SAH and compare the potential degree of impairment. Methods: Subarachnoid hemorrhage was induced by injecting 0.5 ml of heparinized autologous blood into the cisterna magna of male Wistar rats using two anesthesia protocols [isoflurane/fentanyl n = 25 (Sham + SAH): Iso-Group, ketamine/xylazine n = 32 (Sham + SAH): K/X-Group]. CBF (laser speckle contrast analysis) and physiological parameters were measured continuously for 6 h. At six predefined time points, hypercapnia was induced by hypoventilation controlled via blood gas analysis, and retinal vessel diameter (RVD) was determined non-invasively. Results: Cerebral reactivity and retinal reactivity in Sham groups were stable with only a slight attenuation after 2 h in RVD of the K/X-Group. In the SAH Iso-Group, cerebral and retinal CO2 reactivity compared to baseline was immediately impaired starting at 30 min after SAH (CBF p = 0.0090, RVD p = 0.0135) and lasting up to 4 h (p = 0.0136, resp. p = 0.0263). Similarly, in the K/X-Group, cerebral CO2 reactivity was disturbed early after SAH (30 min, p = 0.003) albeit showing a recovery to baseline after 2 h while retinal CO2 reactivity was impaired over the whole observation period (360 min, p = 0.0001) in the K/X-Group. After normalization to baseline, both vascular beds showed a parallel behavior regarding the temporal course and extent of impairment. Conclusion: This study provides a detailed temporal analysis of impaired cerebral vascular CO2 reactivity starting immediately after SAH and lasting up to 6 h. Importantly, the retinal vessels participate in these acute changes underscoring the promising role of the retina as a potential non-invasive screening tool after SAH. Further studies will be required to determine the correlation with functional outcomes.


Field testing of a remote controlled robotic tele-echo system in an ambulance using broadband mobile communication technology.
We report the testing of a mobile Robotic Tele-echo system that was placed in an ambulance and successfully transmitted clear real time echo imaging of a patient's abdomen to the destination hospital from where this device was being remotely operated. Two-way communication between the paramedics in this vehicle and a doctor standing by at the hospital was undertaken. The robot was equipped with an ultrasound probe which was remotely controlled by the clinician at the hospital and ultrasound images of the patient were transmitted wirelessly. The quality of the ultrasound images that were transmitted over the public mobile telephone networks and those transmitted over the Multimedia Wireless Access Network (a private networks) were compared. The transmission rate over the public networks and the private networks was approximately 256 Kbps, 3 Mbps respectively. Our results indicate that ultrasound images of far higher definition could be obtained through the private networks.


Using Modified Equipment in Field Hockey Leads to Positive Transfer of Learning Effect.
Cross-education is the phenomenon in which repeated practice of a unilateral motor task does not only result in performance improvement of the trained limb, but also in the untrained contralateral limb. The aim of this study was to test whether cross-education or positive transfer of learning is also achieved for tasks in which both limbs contribute in different ways by using modified equipment that switches the limbs' role. To this end, a reverse field hockey stick was used that requires a mirroring of arm and hand use and dominance (i.e., right hand on top of the hockey stick instead of the left hand). Two groups of young skilled female field hockey players participated in a crossover-design, in which participants received four training sessions with a reverse hockey stick followed by four training sessions with a regular hockey stick, or vice versa. In a pre-test, intermediate test (following the first intervention period), a post-test (after the second intervention period) and a retention test, participants' performance on a field hockey skill test with a regular hockey stick was measured. The results revealed that training with the reversed hockey stick led to significantly increased improvements compared to training with a regular hockey stick. We conclude that modified equipment can be used to exploit positive transfer of learning by switching the limbs' roles. The findings are discussed by referring to the symmetry preservation principle in dynamic systems theory and have clear practical relevance for field hockey trainers and players seeking to further improve field hockey skills.


Total knee arthroplasty in patients with juvenile idiopathic arthritis.
Total knee arthroplasty (TKA) for juvenile idiopathic arthritis is rare but is nonetheless indicated for many patients with this disease. Few reports exist on the results of TKA in patients with juvenile idiopathic arthritis. It was sought to determine (1) survivorship and (2) functional outcomes of TKAs in patients with juvenile idiopathic arthritis. Results were combined from patients treated by experienced surgeons at five hospitals between 1979 and 2011. Two hundred nineteen patients (349 TKAs) were identified and contacted to survey their outcomes at a minimum followup of 2 years (mean, 12 ± 8 years; range, 2-33 years). The average age at surgery was 28.9 ± 9.7 years (range, 11-58 years). Data on revision surgery and ability to perform daily activities were collected. The 10-year survivorship was 95%, decreasing to 82% by 20 years. At latest followup, 31 of 349 TKAs (8.9%) had been revised for either polyethylene failure or loosening (18 TKAs), infection (four), stiffness (three), periprosthetic fractures (two), bilateral amputation for vascular reasons (two), patellar resurfacing (one), and instability (one). Walking tolerance was unlimited in 49%, five to 10 blocks in 23%, and less than five blocks in 28%. Eleven percent could not manage stairs, and another 59% depended on railings. A cane was used by 12% and crutches by 7%; 12% were wheelchair-dependent. TKA survivorship in patients with juvenile idiopathic arthritis was inferior to that typically seen in younger patients with osteoarthritis or even rheumatoid arthritis confirming results of earlier studies with smaller patient numbers. This is especially disconcerting because younger patients require better durability of their TKAs.


An efficient method of all-optical buffering with ultra-small core photonic crystal fibers.
We propose a new method of all-optical buffering with ultra-small core photonic crystal fibers (PCFs) based on stimulated Brillouin scattering. The large refractive index contrast between the near-hollow cladding and the pure-silica core contributes to high nonlinearity of the PCF. Considering the unusual gain spectrum of the ultra-small core PCF, we numerically investigate the influence of these factors to the buffering efficiency. A PCF with a length of 1 meter and a core diameter of 1.06 micrometer is simulated as the storage medium in this paper. It is shown that we can obtain a good buffering efficiency under a very low control power of 2 watt, which promises a significant improvement for the all-optical communication system.


Internalization of prolactin receptor and prolactin in transfected cells does not involve nuclear translocation.
Prolactin (PRL) interacts with a specific, well characterized plasma membrane receptor (PRLR) that is coupled to signal transduction pathways involving Jak2, Fyn, and MAP kinases, and signal transducers and activators of transcription (STAT). Although a few previous studies have indicated nuclear translocation of PRL in IL-2 stimulated T lymphocytes, PRL-dependent Nb2 lymphoma cell lines and 235-1 lactotrophs, the mechanisms of nuclear targeting remain unknown and conflicting results have been reported concerning the putative nuclear translocation of the PRLR. We therefore decided to investigate nuclear translocation of PRLR and PRL in various cell lines transfected with an expression plasmid encoding PRLR, using confocal laser microscopy. We have constructed various cDNAs of the long and short forms of the rat PRLR containing an oligonucleotide encoding a Flag epitope inserted either just before the N-terminal amino acid or in the C-terminal end of the mature receptor (named N-terminal or C-terminal Flag-tagged PRLR). The corresponding receptors function as the PRLR in transfected cells: they are expressed at the plasma membrane and in compartments of the secretory pathway, they bind PRL with normal affinity (Kd= 4x10(-10) M) and have the same capacity to stimulate the transcriptional activity of a milk protein (beta-casein) gene as wild-type PRLR. In addition, the tagged receptors are much more efficiently immunodetected using anti-Flag antibodies, as compared to anti-PRL antibodies (U5 or U6). Immunofluorescence combined with detailed confocal laser microscopy showed that addition of PRL (0 to 12 hours) to COS-7, CHO and NIH-3T3 transfected fibroblasts induces rapid internalization of the receptor (long form), without any translocation to the nucleus. Using PRL-R tagged both in the N-terminal or C-terminal regions of the mature receptor excludes the possibility of a cleaved fragment which could have been subsequently imported into the nucleus. An absence of nuclear translocation of PRLR was also observed in a 293 cell line stably expressing the receptor, and in physiological targets for PRL, i.e. in Nb2 lymphoma cells expressing the Nb2 form of the receptor or in BGME mammary gland epithelial cells upon overexpression of a Flag-tagged PRLR. Similarly, the short form of the PRLR was not detected in nuclei of transfected COS cells upon PRL treatment. Clearly, our results provide evidence that internalization of the plasma membrane PRLR does not lead to nuclear translocation of the receptor, or part of it, in most fibroblasts and epithelial cells at physiological concentrations of PRL. Also, in co-localization experiments, PRL was internalized without nuclear translocation. Activation of STATs transcription factors and MAP kinases, as well as translocation of these proteins to the nucleus following their phosphorylation, probably remains the intracellular mechanism coupling stimulation to nuclear events.


Multiplex PCR tests sentinel the appearance of pandemic influenza viruses including H1N1 swine influenza.
Since the turn of the century seven new respiratory viruses have infected man and two of these have resulted in worldwide epidemics. Both SARS Coronavirus which quickly spread to 29 countries in February 2003 and H1N1 swine influenza that recently spread from Mexico to 30 countries in three weeks represent major pandemic threats for mankind. Diagnostic assays are required to detect novel influenza strains with pandemic potential. In this report we evaluate the ability of a multiplex PCR test (xTAG RVP) to detect new, "non-seasonal" influenza viruses including the H1N1 swine influenza A/swine/California/04/2009. Laboratory based study using retrospective and prospective specimens. This multiplex PCR test detected the present of non-seasonal (non-H1, non-H3) influenza in 20 of 20 patients infected with H1N1 swine flu virus. In addition to detecting the current swine flu the xTAG RVP test detected the H5N1 A/Vietnam/1203/2004 high pathogenicity avian influenza virus that circulated in South East Asia in 2003 as well as 17 out of 17 influenza A viruses representing 11 HA subtypes isolated from birds, swine and horses not yet seen in the human population. Based on these results we believe that this molecular test can perform an important role as a sentinel test to detect novel non-seasonal influenza A viruses in patients presenting with influenza-like illness (ILI) and therefore act as an early warning system for the detection of future pandemic influenza threats.


Syntactic and discourse skills in Chinese adolescent readers with dyslexia: a profiling study.
This study aims to investigate the relation of syntactic and discourse skills to morphological skills, rapid naming, and working memory in Chinese adolescent readers with dyslexia and to examine their cognitive-linguistic profiles. Fifty-two dyslexic readers (mean age, 13;42) from grade 7 to 9 in Hong Kong high schools were compared with 52 typically developing readers of the same chronological age (mean age, 13;30) in the measures of word reading, 1-min word reading, reading comprehension, morpheme discrimination, morpheme production, morphosyntactic knowledge, sentence order knowledge, digit rapid naming, letter rapid naming, backward digit span, and non-word repetition. Results showed that dyslexic readers performed significantly worse than their peers on all the cognitive-linguistic tasks. Analyses of individual performance also revealed that over half of the dyslexic readers exhibited deficits in syntactic and discourse skills. Moreover, syntactic skills, morphological skills, and rapid naming best distinguished dyslexic from non-dyslexic readers. Findings underscore the significance of syntactic and discourse skills for understanding reading impairment in Chinese adolescent readers.


T Cell Migration from Inflamed Skin to Draining Lymph Nodes Requires Intralymphatic Crawling Supported by ICAM-1/LFA-1 Interactions.
T cells are the most abundant cell type found in afferent lymph, but their migration through lymphatic vessels (LVs) remains poorly understood. Performing intravital microscopy in the murine skin, we imaged T cell migration through afferent LVs in vivo. T cells entered into and actively migrated within lymphatic capillaries but were passively transported in contractile collecting vessels. Intralymphatic T cell number and motility were increased during contact-hypersensitivity-induced inflammation and dependent on ICAM-1/LFA-1 interactions. In vitro, blockade of endothelial cell-expressed ICAM-1 reduced T cell adhesion, crawling, and transmigration across lymphatic endothelium and decreased T cell advancement from capillaries into lymphatic collectors in skin explants. In vivo, T cell migration to draining lymph nodes was significantly reduced upon ICAM-1 or LFA-1 blockade. Our findings indicate that T cell migration through LVs occurs in distinct steps and reveal a key role for ICAM-1/LFA-1 interactions in this process.


Characterization of herpes simplex virus type 1 DNA during latent infection in mice.
Micrococcal nuclease digestion technique in combination with spot-blotting hybridization have been used for the characterization of latent Herpes simplex virus type 1 (HSV-1) DNA in mouse brainstems. Two kinds of samples were used i.e. undigested DNA from mouse brainstems and DNA after prolonged digestion (i.e. for 30 minutes) with micrococcal nuclease from the same source. Each sample contained 5 micrograms of DNA (concentration was measured after digestion with micrococcal nuclease and isolation of DNA). Two kinds of probes were used: -virus specific probe, -host cellular probe. In the performed experiments, we observed the increased susceptibility of latent HSV-1 DNA for micrococcal nuclease digestion, comparing it to host DNA, which may reflect differences in protection of latent viral DNA by nuclear proteins and also may be associated with existing limited transcription of HSV-1 genome during latency.


Course and prognosis of elbow complaints: a cohort study in general practice.
To describe the course of new episodes of elbow complaints in general practice, and to identify predictors of short term and long term outcome in terms of pain intensity and functional disability. 181 patients with elbow complaints filled in questionnaires at baseline and at 3, 6, and 12 months of follow up. Baseline scores of pain and disability, characteristics of the complaint, sociodemographic and psychosocial factors, physical activity, general health, and comorbidity were investigated as possible predictors of outcome. Outcome measures were analysed separately using multiple regression analyses. 13% of the patients reported recovery at the 3 month follow up and 34% at 12 months. Irrespective of outcome and length of follow up, a longer duration of the complaint before consulting the general practitioner, having musculoskeletal comorbidity, and using "retreating" as coping style increased the likelihood of an unfavourable outcome. Less social support was associated with an unfavourable outcome at 3 months, and having a history of elbow complaints and using "worrying" as coping style were associated with an unfavourable outcome at 12 months. The explained variance of the models ranged from 46% to 49%. Recovery of patients with elbow complaints in general practice was poor. Besides characteristic of the complaint, passive coping and less social support were related to a worse prognosis. The results of this study may help general practitioners to provide patients with more accurate information about their prognosis.


Modeling of a high force density fishbone shaped electrostatic comb drive microactuator.
This paper presents the design and evaluation of a high force density fishbone shaped electrostatic comb drive actuator. This comb drive actuator has a branched structure similar to a fishbone, which is intended to increase the capacitance of the electrodes and hence increase the electrostatic actuation force. Two-dimensional finite element analysis was used to simulate the motion of the fishbone shaped electrostatic comb drive actuator and compared against the performance of a straight sided electrostatic comb drive actuator. Performances of both designs are evaluated by comparison of displacement and electrostatic force. For both cases, the active area and the minimum gap distance between the two electrodes were constant. An active area of 800 × 300 μm, which contained 16 fingers of fishbone shaped actuators and 40 fingers of straight sided actuators, respectively, was used. Through simulation, improvement of drive force of the fishbone shaped electrostatic comb driver is approximately 485% higher than conventional electrostatic comb driver. These results indicate that the fishbone actuator design provides good potential for applications as high force density electrostatic microactuator in MEMS systems.


Arrested embryonic development: a review of strategies to delay hatching in egg-laying reptiles.
Arrested embryonic development involves the downregulation or cessation of active cell division and metabolic activity, and the capability of an animal to arrest embryonic development results in temporal plasticity of the duration of embryonic period. Arrested embryonic development is an important reproductive strategy for egg-laying animals that provide no parental care after oviposition. In this review, we discuss each type of embryonic developmental arrest used by oviparous reptiles. Environmental pressures that might have directed the evolution of arrest are addressed and we present previously undiscussed environmentally dependent physiological processes that may occur in the egg to bring about arrest. Areas for future research are proposed to clarify how ecology affects the phenotype of developing embryos. We hypothesize that oviparous reptilian mothers are capable of providing their embryos with a level of phenotypic adaptation to local environmental conditions by incorporating maternal factors into the internal environment of the egg that result in different levels of developmental sensitivity to environmental conditions after they are laid.


Rehabilitation professionals' views on individual peer support interventions for assisting stroke survivors with reintegration into the community: a qualitative study.
We aimed to explore stroke rehabilitation professionals' understanding and representations of peer support; the benefits they anticipated for patients; and the levers and barriers they perceived to implement the intervention in their practice. This qualitative study comprised four focus groups with 21 rehabilitation professionals and four semi-structured interviews. It was held in a French hospital. Interpretation was guided by the Consolidated Framework for Implementation Research. Although professionals had poor knowledge on peer support, they identified many unmet needs of stroke survivors that peer support could meet such as social, emotional and informational support. Main barriers were the lack of human and financial resources, and of linkage between hospital and community professionals, and the fear that peer support would give false hope to survivors if not delivered properly. They showed ambivalence towards patient engagement, acknowledging its importance, but demonstrating top-down attitudes. They also identified potential avenues for the implementation of peer support for stroke survivors. Our study supports the necessity to involve professionals in the construction of peer-support interventions and to sensitise them to provide patient-centred care. It delivers insights on effective implementation strategies to develop peer support interventions for stroke survivors reintegrating the community.


Incarcerated Women's Experiences of Staff-Perpetrated Rape: Racial Disparities and Justice Gaps in Institutional Responses.
Within correctional settings, incarcerated women have disproportionately high rates of experiencing staff-perpetrated sexual victimization. In addition, only a small proportion of incarcerated women formally report their victimization experiences to correctional staff and even fewer reports are fully investigated by internal investigators and found to be substantiated. Given the multiple steps in this process, incarcerated women face several possible justice gaps in receiving preventive and intervention-focused responses from correctional staff. Racial differences among incarcerated women's experiences of these steps have not been explored. This study used a structural intersectional framework to examine racial differences in these areas: incarcerated women's experiences of staff-perpetrated rape, reporting decisions, and correctional staff's investigation decisions. With a sample of 180 incarcerated women, this study included analysis of archival data (i.e., settlement claim forms and internal investigation files) from a class action lawsuit involving incarcerated women who had experienced staff sexual misconduct. Black women represented over half of the incarcerated women who experienced staff-perpetrated rape. There were no statistical differences between Black and White women with regard to the characteristics of their victimization experiences, and they had similar rates of reporting their victimization to institutional staff. However, significant differences were found between women with regard to prison staff's responses to their reports; Black women were less likely to have their reports investigated by staff and were more likely to have their investigated reports found to be unsubstantiated. A detailed analysis of 100 specific incidents showed similar findings. Thus, while justice gaps existed for all women, gaps in institutional responses were exacerbated for Black women. Centering incarcerated Black women's experiences is pivotal for guiding efforts to transform correctional settings, to prevent and address staff-perpetrated sexual victimization, and to build safety for incarcerated women.


In vitro growth and organogenesis of Prosopis farcta plantlets (Fabaceae, Mimosoideae) in culture medium supplemented with various concentrations of Ca++ and Na+.
The objective of this study was to vary the mineral composition of the culture medium of Prosopis farcta seedlings per addition of Na+ and Ca++ ions with the aim to identify the culture media which support the growth and/or the expression of the in vitro plant organogenesis. The Na+ and Ca++ ions were added in the culture medium in various concentrations by taking the Gamborg medium, in which macroelements were diluted 10 times, as the basic one. After two months of culture, parameters relating to the vegetative development of plant seedlings and to the various expressions of organogenesis were measured. Weak concentrations in sodium and calcium ions as well as a weak concentration in Ca++ (0.1 mM) with 50 mM in Na+ support the best vegetative development of the plantlets. The most important percentage of plant seedlings presenting a bud initiation was obtained on a medium containing 0.1 mM of Na+ and 50 mM of Ca++. Our study defined several media likely to support in vitro development of Prosopis farcta plantlets allowing the selection of salt tolerant plants or cellular lines. Some other media were chosen for improving micropropagation of the species without adding growth substances.


Local neutral networks help maintain inaccurately replicating ribozymes.
The error threshold of replication limits the selectively maintainable genome size against recurrent deleterious mutations for most fitness landscapes. In the context of RNA replication a distinction between the genotypic and the phenotypic error threshold has been made; where the latter concerns the maintenance of secondary structure rather than sequence. RNA secondary structure is treated as a proxy for function. The phenotypic error threshold allows higher per digit mutation rates than its genotypic counterpart, and is known to increase with the frequency of neutral mutations in sequence space. Here we show that the degree of neutrality, i.e. the frequency of nearest-neighbour (one-step) neutral mutants is a remarkably accurate proxy for the overall frequency of such mutants in an experimentally verifiable formula for the phenotypic error threshold; this we achieve by the full numerical solution for the concentration of all sequences in mutation-selection balance up to length 16. We reinforce our previous result that currently known ribozymes could be selectively maintained by the accuracy known from the best available polymerase ribozymes. Furthermore, we show that in silico stabilizing selection can increase the mutational robustness of ribozymes due to the fact that they were produced by artificial directional selection in the first place. Our finding offers a better understanding of the error threshold and provides further insight into the plausibility of an ancient RNA world.


Transgenic expression of soluble human CD5 enhances experimentally-induced autoimmune and anti-tumoral immune responses.
CD5 is a lymphoid-specific transmembrane glycoprotein constitutively expressed on thymocytes and mature T and B1a lymphocytes. Current data support the view that CD5 is a negative regulator of antigen-specific receptor-mediated signaling in these cells, and that this would likely be achieved through interaction with CD5 ligand/s (CD5L) of still undefined nature expressed on immune or accessory cells. To determine the functional consequence of loss of CD5/CD5L interaction in vivo, a new transgenic mouse line was generated (shCD5EμTg), expressing a circulating soluble form of human CD5 (shCD5) as a decoy to impair membrane-bound CD5 function. These shCD5EμTg mice showed an enhanced response to autologous antigens, as deduced from the presentation of more severe forms of experimentally inducible autoimmune disease (collagen-induced arthritis, CIA; and experimental autoimmune encephalitis, EAE), as well as an increased anti-tumoral response in non-orthotopic cancer models (B16 melanoma). This enhancement of the immune response was in agreement with the finding of significantly reduced proportions of spleen and lymph node Treg cells (CD4+CD25+FoxP3+), and of peritoneal IL-10-producing and CD5+ B cells, as well as an increased proportion of spleen NKT cells in shCD5EμTg mice. Similar changes in lymphocyte subpopulations were observed in wild-type mice following repeated administration of exogenous recombinant shCD5 protein. These data reveal the relevant role played by CD5/CD5L interactions on the homeostasis of some functionally relevant lymphocyte subpopulations and the modulation of immune responses to autologous antigens.


Optimizing Signal Management in a Vaccine Adverse Event Reporting System: A Proof-of-Concept with COVID-19 Vaccines Using Signs, Symptoms, and Natural Language Processing.
The Vaccine Adverse Event Reporting System (VAERS) has already been challenged by an extreme increase in the number of individual case safety reports (ICSRs) after the market introduction of coronavirus disease 2019 (COVID-19) vaccines. Evidence from scientific literature suggests that when there is an extreme increase in the number of ICSRs recorded in spontaneous reporting databases (such as the VAERS), an accompanying increase in the number of disproportionality signals (sometimes referred to as 'statistical alerts') generated is expected. The objective of this study was to develop a natural language processing (NLP)-based approach to optimize signal management by excluding disproportionality signals related to listed adverse events following immunization (AEFIs). COVID-19 vaccines were used as a proof-of-concept. The VAERS was used as a data source, and the Finding Associated Concepts with Text Analysis (FACTA+) was used to extract signs and symptoms of listed AEFIs from MEDLINE for COVID-19 vaccines. Disproportionality analyses were conducted according to guidelines and recommendations provided by the US Centers for Disease Control and Prevention. By using signs and symptoms of listed AEFIs, we computed the proportion of disproportionality signals dismissed for COVID-19 vaccines using this approach. Nine NLP techniques, including Generative Pre-Trained Transformer 3.5 (GPT-3.5), were used to automatically retrieve Medical Dictionary for Regulatory Activities Preferred Terms (MedDRA PTs) from signs and symptoms extracted from FACTA+. Overall, 17% of disproportionality signals for COVID-19 vaccines were dismissed as they reported signs and symptoms of listed AEFIs. Eight of nine NLP techniques used to automatically retrieve MedDRA PTs from signs and symptoms extracted from FACTA+ showed suboptimal performance. GPT-3.5 achieved an accuracy of 78% in correctly assigning MedDRA PTs. Our approach reduced the need for manual exclusion of disproportionality signals related to listed AEFIs and may lead to better optimization of time and resources in signal management.


The effect of music on robot-assisted laparoscopic surgical performance.
Music is often played in the operating room to increase the surgeon's concentration and to mask noise. It could have a beneficial effect on surgical performance. Ten participants with limited experience with the da Vinci robotic surgical system were recruited to perform two surgical tasks: suture tying and mesh alignment when classical, jazz, hip-hop, and Jamaican music were presented. Kinematics of the instrument tips of the surgical robot and surface electromyography of the subjects were recorded. Results revealed that a significant music effect was found for both tasks with decreased time to task completion (P = .005) and total travel distance (P = .021) as well as reduced muscle activations ( P = .016) and increased median muscle frequency (P = .034). Subjects improved their performance significantly when they listened to either hip-hop or Jamaican music. In conclusion, music with high rhythmicity has a beneficial effect on robotic surgical performance. Musical environment may benefit surgical training and make acquisition of surgical skills more efficient.


[Innovative use of the vascular endothelial growth factor in an experimental model of acute liver failure].
Vascular Endothelial Growth Factor (VEGF) is an endothelial cell mitogen and an important stimulator of sinusoidal endothelial cell proliferation. The aim of this research was to study the effects of exogenous VEGF in a rat model of acute liver failure. The study was conducted on 64 rats (240-300 g). All rats underwent intraperitoneal injection (5 ml/kg) of 25% carbon tetrachloride (CCl4) and 75% paraffin oil. This dosage of CCl4 was devised to induce nonfatal acute liver failure with spontaneous recovery in 7 days. The animals were randomly divided into 2 groups. Group B animals underwent i.v. injection of 200 ng of VEGF165 one hour following intra-peritoneal injection of CCl4. To obtain daily liver functional tests (LFTS) and histological liver samples, 4 rats in each group were sacrificed daily up to 8 days. In group A, the liver histology showed massive periportal hepatocyte necrosis associated with portal lymphocytic infiltrates. The peak of the damage was documented at 72 hours following CCl4. Group B showed minimal necrosis, moderate periportal edema and a minimum periportal steatosis. At 48 hours steatotic changes had disappeared and the periportal edema was resolving. LFTs demonstrated severe liver damage in rats in group A. In group A the peak AST (mean 322.5 IU/L) and ALT (mean 250.25 IU/L) were recorded at 72 hours. In group B, at 72 hours the mean AST was 137 IU/L (normal < 95 IU/L) and ALT 68 IU/L(normal < 45 IU/L). The maximum levels of AST and ALT, in group B, were 152.3 IU/L and 72.3 IU/L, at 24 hours. According to our results exogenous VEGF successfully protects the liver from CCl4 induced acute liver failure. Further studies will demonstrate if exogenous VEGF can be effective in other liver injuries.


A unified first-order hyperbolic model for nonlinear dynamic rupture processes in diffuse fracture zones.
Earthquake fault zones are more complex, both geometrically and rheologically, than an idealized infinitely thin plane embedded in linear elastic material. To incorporate nonlinear material behaviour, natural complexities and multi-physics coupling within and outside of fault zones, here we present a first-order hyperbolic and thermodynamically compatible mathematical model for a continuum in a gravitational field which provides a unified description of nonlinear elasto-plasticity, material damage and of viscous Newtonian flows with phase transition between solid and liquid phases. The fault geometry and secondary cracks are described via a scalar function ξ ∈ [0, 1] that indicates the local level of material damage. The model also permits the representation of arbitrarily complex geometries via a diffuse interface approach based on the solid volume fraction function α ∈ [0, 1]. Neither of the two scalar fields ξ and α needs to be mesh-aligned, allowing thus faults and cracks with complex topology and the use of adaptive Cartesian meshes (AMR). The model shares common features with phase-field approaches, but substantially extends them. We show a wide range of numerical applications that are relevant for dynamic earthquake rupture in fault zones, including the co-seismic generation of secondary off-fault shear cracks, tensile rock fracture in the Brazilian disc test, as well as a natural convection problem in molten rock-like material. This article is part of the theme issue 'Fracture dynamics of solid materials: from particles to the globe'.


Effects of aerobic exercise intensity on 24-h ambulatory blood pressure in individuals with type 2 diabetes and prehypertension.
[Purpose] To verify the effects of different intensities of aerobic exercise on 24-hour ambulatory blood pressure (BP) responses in individuals with type 2 diabetes mellitus (T2D) and prehypertension. [Subjects and Methods] Ten individuals with T2D and prehypertension (55.8 ± 7.7 years old; blood glucose 133.0 ± 36.7 mg·dL(-1) and awake BP 130.6 ± 1.6/ 80.5 ± 1.8 mmHg) completed three randomly assigned experiments: non-exercise control (CON) and exercise at moderate (MOD) and maximal (MAX) intensities. Heart rate (HR), BP, blood lactate concentrations ([Lac]), oxygen uptake (VO2), and rate of perceived exertion (RPE) were measured at rest, during the experimental sessions, and during the 60 min recovery period. After this period, ambulatory blood pressure was monitored for 24 h. [Results] The results indicate that [Lac] (MAX: 6.7±2.0 vs. MOD: 3.8±1.2 mM), RPE (MAX: 19±1.3 vs. MOD: 11±2.3) and VO2peak (MAX: 20.2±4.1 vs. MOD: 14.0±3.0 mL·kg(-1)·min(-1)) were highest following the MAX session. Compared with CON, only MAX elicited post-exercise BP reduction that lasted for 8 h after exercise and during sleep. [Conclusion] A single session of aerobic exercise resulted in 24 h BP reductions in individuals with T2D, especially while sleeping, and this reduction seems to be dependent on the intensity of the exercise performed.


Transcriptional organization of the Escherichia coli hemolysin genes.
The transcriptional organization of the Escherichia coli hemolysin genes (hlyCABD) encoded by pSF4000 was examined. The use of different hemolysin gene-specific radiolabeled probes in blots containing isolated in vivo RNA revealed 4.0-kilobase hlyCA and 8.0-kilobase hlyCABD transcripts. The treatment of cells with rifampin just before RNA isolation showed the half-lives of these mRNAs to be 10.2 and 4.4 min, respectively. The 5' ends of the hly transcripts were 462 and 464 nucleotides from the putative initiation codon of hlyC based on a primer extension method of RNA mapping. Deletion analysis of pSF4000 combined with quantification of the hemolysin structural protein HlyA by immunoblotting confirmed that major control of HlyA expression occurs within a 168-base-pair PstI fragment located 433 base pairs upstream of the start of hlyC. A second recombinant plasmid, pANN202-312, encoding an E. coli hemolysin of different origin expressed 6-fold less total HlyA and 50-fold less extracellular HlyA than pSF4000 in identical cell backgrounds. The pANN202-312 recombinant had a different hly promoter, with the hly mRNA beginning 264 nucleotides upstream from the start of hlyC. We showed by RNA blotting that cells harboring pANN202-312 compared with pSF4000 have similar steady-state levels of the hlyCA transcript but they lack a consistently detectable hlyCABD transcript. We propose that one reason for the disparate levels of extracellular hemolysin produced by hemolytic E. coli is dissimilar levels of mRNA encoding in part the transport genes hlyB and hlyD.


Determination of nitrofuran and chloramphenicol residues by high resolution mass spectrometry versus tandem quadrupole mass spectrometry.
An ultra-high performance liquid chromatography based method, coupled to high resolution mass spectrometry (UHPLC-HRMS), was developed to permit the detection and quantification of various nitrofuran and chloramphenicol residues in a number of animal based food products. This method is based on the hydrolysis of covalently bound metabolites and derivatization with 2-nitrobenzaldehyde. Clean-up is achieved by a liquid/liquid and a reversed phase/solid phase extraction. Not only are the four conventional nitrofurans (nitrofurantoin, furazolidone, nitrofurazone and furaltadone) detected, but also nifursol, nitrovin and nifuroxazide. Furthermore, an underivatizable nitrofuran (nifurpirinol) and another banned drug (chloramphenicol) can be quantified as well. The compounds are detected in the form of their precursor ions, [M+H](+) and [M-H](-), respectively. The mass resolving power of 70,000 FWHM, and the applied mass window ensure sufficient selectivity and sensitivity. Confirmation is obtained by monitoring the HRMS resolved product ions which were derived from the unit-mass resolved precursor ions. The multiplexing capability of the utilized Orbitrap instrument provides not only highly selective, but also sensitive confirmatory signals. This method has been validated according to the CD 2002/657/EC for the following matrices: muscle, liver, kidney, fish, honey, eggs and milk.


The validation of an educational database for children with profound intellectual disabilities.
The Western Cape Forum for Intellectual Disability took the South African Government to court in 2010 on its failure to implement the right to education for Children with Severe and Profound Intellectual Disability. Subsequently, multidisciplinary teams were appointed by the Western Cape Education Department to deliver services to the Special Care Centres (SCCs). Initially, minimal information was available on this population. The purpose is to document the process of developing and validating a database for the collection of routine data. A descriptive analytical study design was used. A sample of convenience was drawn from individuals under the age of 18 years, enrolled in SCCs in the Western Cape. The team who entered and analysed the data reached consensus regarding the utility and feasibility of each item. Data were collected on 134 children. The omission of certain items from the database was identified. Some information was not reliable or readily available. Of the instruments identified to assess function, the classification systems were found to be reliable and useful, as were the performance scales. The WeeFIM, on the other hand, was lengthy and expensive, and was therefore discarded. A list of items to be included was identified. Apart from an individual profile, it can be useful for service planning and monitoring, if incorporated into the central information system used to monitor the performance of all children. Without such inclusion, this most vulnerable population, despite court ruling, will not have their right to education adequately addressed.


Effects of meal composition on gallbladder and gastric emptying in man.
Cholecystogastric scintigraphy, utilizing [99mTc]HlDA to label the gallbladder contents and [111In]DTPA to label different meals, was utilized to determine the relationships between gallbladder and gastric emptying after meals of differing composition. Gallbladder emptying was determined in response to a multicomponent meal and to monocomponent fat, carbohydrate, and protein meals and in response to isotonic and hypertonic dextrose and isotonic and hypertonic saline. Also, the gallbladder emptying responses to equivalent multicomponent solid and liquid meals were compared. Significant gallbladder emptying was observed in response to the multicomponent meal and the monocomponent fat, carbohydrate, and protein meals. The most rapid and complete gallbladder emptying was seen with the multicomponent meal and the monocomponent fat meal. Significant gallbladder emptying was stimulated, not only by isotonic and hypertonic dextrose, but also by hypertonic saline. The gallbladder emptied more rapidly after a liquid than after a solid meal.


[Perinatal model of human transition from hypogravity to the earth's gravity based on the electromyogram nonlinear characteristics].
Interferential electromyogram (iEMG) was analyzed in healthy newborn infants (n=29) during the first 24 hours of life as a model of transition from hypogravity (intrauterine immersion) to the Earth's gravity (postnatal period). Nonlinear instruments of iEMG analysis (correlation dimension, entropy and fractal dimension) reflected the complexity, chaotic character and predictability of signals from the leg and arm antagonistic muscles. Except for m. gastrocnemius, in all other musles iEMG fractal dimension was shown to grow as the postnatal period extended. Low fractal and correlation dimensions and entropy marked flexor muscles, particularly against low iEMG amplitude suggesting a better congenital programming for the flexors as compared to the extensors. It is concluded that the early ontogenesis model can be practicable in studying the evolution and states of antigravity functions.


Applying an artificial neural network model for developing a severity score for patients with hereditary amyloid polyneuropathy.
Hereditary (familial) amyloid polyneuropathy (FAP) is a systemic disease that includes a sensorimotor polyneuropathy related to transthyretin (TTR) mutations. So far, a scale designed to classify the severity of this disease has not yet been validated. This work proposes the implementation of an artificial neural network (ANN) in order to develop a severity scale for monitoring the disease progression in FAP patients. In order to achieve this goal, relevant symptoms and laboratory findings were collected from 98 Brazilian patients included in THAOS - the Transthyretin Amyloidosis Outcomes Survey. Ninety-three percent of them bore Val30Met, the most prevalent variant of TTR worldwide; 63 were symptomatic and 35 were asymptomatic. These data were numerically codified for the purpose of constructing a Self-Organizing Map (SOM), which maps data onto a grid of artificial neurons. Mapped data could be clustered by similarity into five groups, based on increasing FAP severity (from Groups 1 to 5). Most symptoms were virtually absent from patients who mapped to Group 1, which also includes the asymptomatic patients. Group 2 encompasses the patients bearing symptoms considered to be initial markers of FAP, such as first signs of walking disabilities and lack of sensitivity to temperature and pain. Interestingly, the patients with cardiac symptoms, which also carry cardiac-associated mutations of the TTR gene (such as Val112Ile and Ala19Asp), were concentrated in Group 3. Symptoms such as urinary and fecal incontinence and diarrhea characterized particularly Groups 4 and 5. Renal impairment was found almost exclusively in Group 5. Model validation was accomplished by considering the symptoms from a sample with 48 additional Brazilian patients. The severity scores proposed here not only identify the current stage of a patient's disease but also offer to the physician an easy-to-read, 2D map that makes it possible to track disease progression.


Premenstrual syndrome as a criminal defense.
Premenstrual syndrome may be effective as an affirmative defense to a criminal charge if the defendant can show that (i) she was suffering from premenstrual syndrome at the time the crime was committed; and (ii) because of her condition, either that the criminal act was an involuntary act or that at the time of the criminal act she did not possess the mental state required by law for the commission of a crime. Premenstrual syndrome has been successfully pleaded as a criminal defense in Great Britain but has not been tested in American criminal courts. It may now be possible, however, because of the increase of behavioral, psychological, and physiological studies precisely characterizing premenstrual syndrome and elucidating the necessary criteria for its accurate diagnosis, for the appropriate defendant to assert this defense in an American court. This paper discusses (i) the use of recent scientific data to demonstrate the existence of premenstrual syndrome; (ii) the use of standardized psychological tests or physiological assays to demonstrate that the defendant suffers from premenstrual syndrome; and, (iii) the legal choices to be made and evidentiary hurdles that must be overcome in presenting a premenstrual syndrome defense.


Expectations of filial obligation and their impact on preferences for future living arrangements of middle-aged and older Asian Indian immigrants.
Filial obligation, described as culturally-defined rights and duties that prescribe how family members are expected to care for and provide support to each other, is an important variable that influences older immigrants' preferences for living and care arrangements. This exploratory study examined variables associated with expectations of filial obligation among middle-aged and older, Asian Indian, first generation immigrants and explored the relationship between variations in expectations of filial obligation and expressed preferences for future living arrangements. Data were collected through telephone surveys of 226 English-speaking immigrants in Atlanta, GA. Although no significant relationships were observed between filial obligation expectations and length of residence in the U.S., respondents indicated a variety of preferred future living arrangements. Contrary to current living arrangement patterns found among older immigrants, very few respondents preferred to move in with their children. The most popular preference was to "move closer to children," followed by "moving to a retirement community" with the majority preferring a retirement community geared to Asian Indians. Other preferences included "not moving" and "returning to India." Variations in expectations of filial obligation, length of residence in the U.S., and self-rated health were significantly associated with these preferences. Implications are discussed for building capacity within ethnic communities to address living arrangement preferences and their repercussions for caregiving in ethnic families and in communities.


Characteristics and natural history of transient postoperative pseudosubluxation after total hip arthroplasty.
A series of 13 total hip arthroplasties (THAs) in which immediate postoperative radiographs revealed axial subluxation were reviewed, and the timing, incidence, and subsequent natural history of this phenomenon were determined. Each patient had received perioperative epidural anesthesia and was placed in an abduction splint before transfer to the postoperative care unit. All initial radiographs were taken while the patient was still under the effect of the epidural anesthetic agent (average, 54 minutes; range, 37-80 minutes) postoperatively. In each case, radiographs taken after anesthetic recovery and without limb manipulation revealed reduced components. The balance of the postoperative care and rehabilitation was uncomplicated; patients were followed at least 36 months postoperatively, and in only 1 patient did a subsequent hip dislocation occur. Over a 6-month period, the postoperative films of all THAs were studied, and postoperative subluxation was identified in about 3% of the cases. Postoperative subluxation is likely to be noted when the radiograph is obtained within 1 hour of transfer to the postoperative care unit. It does not appear to have a dramatic effect on the rate of postoperative dislocation, however. This radiographic finding probably is due to the continued effects of regional anesthesia, and reduction occurs as muscle tone returns. If transient subluxation is identified, no change in postoperative care is necessary.


Multiple outbreaks for the same pandemic: Local transportation and social distancing explain the different "waves" of A-H1N1pdm cases observed in México during 2009.
Influenza outbreaks have been of relatively limited historical interest in Mexico. The 2009 influenza pandemic not only changed Mexico's health priorities but also brought to the forefront some of the strengths and weaknesses of Mexico's epidemiological surveillance and public health system. A year later, Mexico's data show an epidemic pattern characterized by three "waves''. The reasons this three-wave patterns are theoretically investigated via models that incorporate Mexico's general trends of land transportation, public health measures, and the regular opening and closing of schools during 2009. The role of vaccination is also studied taking into account delays in access and limitations in the total and daily numbers of vaccines available. The research in this article supports the view that the three epidemic "waves" are the result of the synergistic interactions of three factors: regional movement patterns of Mexicans, the impact and effectiveness of dramatic social distancing measures imposed during the first outbreak, and the summer release of school children followed by their subsequent return to classes in the fall. The three "waves" cannot be explained by the transportation patterns alone but only through the combination of transport patterns and changes in contact rates due to the use of explicit or scheduled social distancing measures. The research identifies possible vaccination schemes that account for the school calendar and whose effectiveness are enhanced by social distancing measures. The limited impact of the late arrival of the vaccine is also analyzed.


[Wilms tumor of the adult. Description of a case and review of the literature].
Wilms tumour is an infantile neoplasia with low incidence in adults. Worldwide literature describes 260 cases but only 50 meet the diagnostic criteria described by Kilton. This paper presents one case diagnosed in our service and includes a review of the literature.


A child with a novel de novo mutation in the aristaless domain of the aristaless-related homeobox (ARX) gene presenting with ambiguous genitalia and psychomotor delay.
The objective of this study was to identify disease-causing mutations in a Sri Lankan male child presenting with ambiguous genitalia and psychomotor delay using the exome sequencing approach. A novel mutation in the aristaless-related homeobox (ARX) gene causing a hemizygous nucleotide substitution in exon 5 was identified (NM_139058.2 (ARX): c.1614G>T; p.K538N). This change causes a nonsynonymous substitution in the aristaless domain within the ARX protein which is predicted to be deleterious. This is the first reported case of ambiguous genitalia and psychomotor delay associated with this novel missense mutation within the ARX protein, and it highlights the value of exome sequencing even in sporadic cases.


Porphyrin abnormalities in acquired immunodeficiency syndrome.
To examine prospectively porphyrin metabolism in a human immunodeficiency virus (HIV)-positive population. Specialist referral unit at the Department of Genitourinary Medicine, St James's Hospital, Dublin, Ireland. Twenty-eight men and 5 women (age range, 18-35 years). Twenty-nine were current or previous intravenous drug abusers. Four were thought to have sexually acquired HIV infection. All had a history of acquired immunodeficiency syndrome-defining illnesses. The patients were selected as a consecutive sample from the inpatient department. Eligibility criteria were cooperation with urine and stool collection and confirmed HIV seropositivity. The patients were matched to 2 groups: 1 with normal results of porphyrin studies and the other with abnormal findings from porphyrin studies. None. Plasma, urine, and stool porphyrin excretion patterns. Of the 33 patients in the study, 13 (40%) had increased urinary porphyrin excretion. All but 2 of these patients were seropositive for hepatitis C virus. No study patient had clinical evidence of porphyria. Four patients (12%), however, had urine and stool porphyrin excretion patterns that were classic for porphyria cutanea tarda. All 4 of these patients were hepatitis C virus-positive. Patients with porphyrinuria had a greater degree of immunosuppression (P = .002) than those with normal porphyrin metabolism, and they were more likely to be taking zidovudine (P = .009). Commonly, porphyrin metabolism is abnormal in persons with established HIV infection. Hepatitis C may contribute to abnormal porphyrin metabolism. An unexpected number of patients studied had porphyrin excretion patterns that were characteristic of porphyria cutanea tarda, and all of these were hepatitis C virus-positive. A diagnosis of porphyria cutanea tarda, especially in a young patient, should prompt investigation for underlying HIV and hepatitis C virus infections. Dermatologists should be aware of the infectious risk associated with the vesicles and erosions in these patients. Porphyrin studies should be performed in any patient with HIV and photosensitivity.


[Neurography for diagnosing carpal tunnel syndrome].
A number of evidence-based guidelines now recommend that a nerve conduction study should be used to confirm the existence of carpal tunnel syndrome before any surgery takes place. The article is based on a search in PubMed, a personal literature archive (1980-2011) and long clinical experience of neurological and neurophysiological diagnostics. Both motor and sensory nerve fascicles must be tested after adequate warming up. An extended nerve conduction study with supplementary tests to compare velocities and latencies in median and ulnar nerves, increases the diagnostic precision. Given normal or mild findings, surgery can usually be avoided as the first choice of treatment, because many patients with mild carpal tunnel syndrome recover spontaneously. The gold standard for diagnosis of carpal tunnel syndrome should be a combination of a clinical examination and a nerve conduction study.


Communication skills and error in the intensive care unit.
Poor communication in critical care teams has been frequently shown as a contributing factor to adverse events. There is now a strong emphasis on identifying the communication skills that can contribute to, or protect against, preventable medical errors. This review considers communication research recently conducted in the intensive care unit and other acute domains. Error studies in the intensive care unit have shown good communication to be crucial for ensuring patient safety. Interventions to improve communication in the intensive care unit have resulted in reduced reports of adverse events, and simulated emergency scenarios have shown effective communication to be correlated with improved technical performance. In other medical domains where communication is crucial for safety, the relationship between communication skills and error has been examined more closely, with highly detailed teamwork assessment tools being developed. Critical care teams perform many activities where effective communication is crucial for ensuring patient safety and reducing susceptibility to error. To develop valid team training and assessment tools for improving teamwork in the intensive care unit there is a requirement to better understand and identify the specific communication skills important for safety during the provision of intensive care medicine.


Nuclear hormone receptors inhibit matrix metalloproteinase (MMP) gene expression through diverse mechanisms.
Agents like retinoids, thyroid hormone, glucocorticoids, progesterone, androgens, which bind to members of the nuclear receptor superfamily, inhibit the synthesis of matrix metalloproteinases (MMPs) in many cell types. These Zn2(+)- and Ca2(+)-dependent MMPs degrade components of the extracellular matrix (ECM), and precise regulation of their expression is crucial in many normal processes. However, inappropriate expression of MMPs contributes to a variety of invasive and erosive diseases, and inhibition of MMP synthesis provides an important mechanism for controlling such aberrant or dysregulated responses. Nuclear receptors control MMPs through a variety of seemingly redundant mechanisms. First, nuclear receptors act on the promoters of MMP genes to enhance or suppress trans-activation. Ironically, in a family of genes that exhibits substantial regulation by nuclear receptors, few consensus hormone responsive elements (HREs) have been deomonstrated in MMP promoters. Rather, inhibition of MMPs occurs primarily, but not exclusively, at AP-1 sites. Here, nuclear receptors form complexes on the DNA through interactions with AP-1 proteins, sequester Fos/Jun and/or decrease the mRNAs for these transcription factors. Second, nuclear receptors and their ligands can indirectly inhibit MMPs. For instance, both retinoids and glucocorticoids induce the transcription of TIMPs (tissue inhibitor of metalloproteinases), which complex with MMPs and inhibit enzymatic activity, and progesterone stimulates production of transforming growth factor-beta (TGF-beta), which in turn suppresses MMP-7 (matrilysin). Finally, nuclear receptors bind to coactivators, corepressors, and components of the general transcriptional apparatus, but the potential role of these interactions in MMP regulation remains to be determined. We conclude that nuclear receptors utilize multiple, apparently redundant, mechanisms to inhibit MMP gene expression, assuring precise control of ECM degradation under a variety of physiologic and pathologic conditions.


13C-n.m.r. study of C hordein.
The structure of C hordein was studied by a combination of solution and solid-state 13C-n.m.r. spectroscopy. The repetitive primary structure results in simple solution-state n.m.r. spectra, which allow assignment of the majority of the resonances to five major residues. The major resonances, with the exception of the aromatic signals, are also present in the solid-state spectra. The proline residues are in the trans configuration, consistent with an earlier study suggesting a beta-turn-rich structure.


Development of a flexible inflow cannula with titanium inflow tip for the NEDO biventricular assist device.
A newly designed flexible inflow cannula has been developed for a biventricular assist device (BVAD). The inflow tip was designed for long-term ventricle drainage. Considering the anatomic differences between the right and left ventricles, a flexible inflow cannula, as a mass production model with a titanium tip, was developed and investigated in chronic BVAD animal experiments using the NEDO permanently implantable centrifugal blood pump. These flexible inflow cannulae consist of flexible plastic tubing with wire supported, titanium left and right tips. The right titanium inflow tip was designed with inner and outer stoppers to be inserted into the right ventricle wall and a beak shape to avoid sucking. The left tip was designed to be inserted into the left ventricle cavity. Five chronic BVAD bovine studies were performed to investigate the new beak shaped titanium tip. In these studies, the new beak shaped titanium tip and cannula prevented stenosis by a proliferation of pseudoneointimal, and supplied adequate blood flow to the pump without sucking. This newly designed inflow cannula with the beak shaped titanium tip was successfully implanted for 90 days.


[Treatment policy for postoperative complications in patients with hepatic echinococcosis and bile duct affection].
Results of surgical treatment of 277 patients with hepatic echinococcosis and bile duct affection demonstrated that the rate of specific postoperative complications depends on duration of the disease, location and size of the parasitic cyst, changes in the cyst (suppuration, calcification), and also on the level of the lesion in the bile ducts. They were seen in the lesion of the segmental ducts 1.5 times less (18%) often than in the lesion of the hepatic ducts (25.7%). Early diagnosis, adequate surgical treatment, characteristics of pathological alterations in the cyst and bile ducts influence treatment outcomes. Postoperative complications arose in 25.9% cases with lethality 1.4%. These complications were diagnosed 6 times less often after elimination of the residual cavity, suturing of bile fistulas or other methods (resection, pericyctectomy) application than after drainage of the residual cavity.


tax and rex Sequences of bovine leukaemia virus from globally diverse isolates: rex amino acid sequence more variable than tax.
Bovine leukaemia virus (BLV) is an important agricultural problem with high costs to the dairy industry. Here, we examine the variation of the tax and rex genes of BLV. The tax and rex genes share 420 bases and have overlapping reading frames. The tax gene encodes a protein that functions as a transactivator of the BLV promoter, is required for viral replication, acts on cellular promoters, and is responsible for oncogenesis. The rex facilitates the export of viral mRNAs from the nucleus and regulates transcription. We have sequenced five new isolates of the tax/rex gene. We examined the five new and three previously published tax/rex DNA and predicted amino acid sequences of BLV isolates from cattle in representative regions worldwide. The highest variation among nucleic acid sequences for tax and rex was 7% and 5%, respectively; among predicted amino acid sequences for Tax and Rex, 9% and 11%, respectively. Significantly more nucleotide changes resulted in predicted amino acid changes in the rex gene than in the tax gene (P < or = 0.0006). This variability is higher than previously reported for any region of the viral genome. This research may also have implications for the development of Tax-based vaccines.


Polysomnography as a diagnosis and post-treatment follow-up tool in human African trypanosomiasis: a case study in an infant.
Gambian (Trypanosoma brucei gambiense) human African trypanosomiasis (HAT) evolves from the hemolymphatic stage 1, treated with pentamidine, to the meningoencephalitic stage 2, often treated with melarsoprol. This arseniate may provoke a deadly reactive encephalopathy. It is therefore crucial to diagnose precisely the stages of HAT, especially when clinical and biological examinations are doubtful. We present here the case of a 30-month old girl (E20 KOLNG) diagnosed with stage 1 HAT during a field survey in June 2007 in Congo. She was followed-up every six months for 18 months in a village dispensary facility at Mpouya. Her health status deteriorated in December 2008, although cerebrospinal fluid (CSF) white blood cell (WBC) count was normal. The child was hospitalized at Brazzaville and a daytime polysomnographic recording (electroencephalogram, electrooculogram, and electromyogram) was performed (Temec Vitaport 3® portable recorder) to avoid a new lumbar puncture. The child presented a complete polysomnographic syndrome of HAT with a major disturbance of the distribution of sleep and wake episodes and the occurrence of sleep onset REM periods (SOREMPs). The relapse at stage 2 was confirmed by a new CSF examination that showed an elevated WBC count (23cells·μL(-1)) with the presence of B lymphocytes. Melarsoprol treatment was undertaken. A post-treatment recording was immediately performed, showing the resolution of sleepwake pattern abnormalities. Another polysomnography, taken four months later, confirmed the normalization of sleep-wake patterns indicating healing. We therefore propose that polysomnography, being a non-invasive technique, should be used in children to alleviate burden caused by HAT staging procedures, especially regarding lumbar punctures in remote African villages.


Perspectives on low-density lipoprotein cholesterol goal achievement.
Elevated levels of low-density lipoprotein cholesterol (LDL-C) are associated with an increased risk of coronary heart disease (CHD). European and US guidelines now recommend lower LDL-C levels, particularly in high-risk patients. Although LDL-C treatment goals to reduce the risk of CHD are clear, many patients do not reach their LDL-C goals. Examine consensus guideline targets for LDL-C lowering in patients at high or very high cardiovascular risk; examine cholesterol goal achievement in clinical practice; evaluate the effectiveness of ezetimibe/statin and other adjunctive lipid-lowering treatments in achieving LDL-C goals; and consider ongoing controversies and the randomized controlled trials that may help to resolve or better illuminate them. An English-language PubMed search was conducted to identify prospective randomized controlled trials, open-label studies, and retrospective and observational studies from 2001 (same year that the executive summary of the National Cholesterol Education Program's Adult Treatment Panel III was published) to present for an analysis of the effects of adjunctive therapies on LDL-C lowering and goal attainment in patients at elevated cardiovascular risk. Elevated LDL-C is the primary target of lipid-lowering therapy; aggressive lowering is of great benefit to those at high risk. Statins are recommended first-line lipid-lowering agents, with a long, well-regarded history of efficacy and safety. Not all patients, however, can achieve recommended LDL-C goals simply using starting doses of statins. For such patients, more intensive therapy utilizing high-dose statins or combination therapy, including statins combined with other lipid-lowering agents, such as ezetimibe, bile acid resins (BARs), or niacin, is warranted. Potential limitations of the present review include possible publication bias and the focus on pharmacotherapy rather than lifestyle modification and the important objective of multiple risk-factor modification to reduce absolute global cardiovascular risk. With a well-established link between elevated LDL-C and cardiovascular risk, aggressive LDL-C lowering becomes particularly important. Patients needing intensive LDL-C lowering to achieve goals will often require adjunctive treatments, including ezetimibe, BARs, or niacin along with statins. Given both their high mg: mg potency in lowering LDL-C and favorable tolerability and patient acceptance/adherence profile, ezetimibe/statin combination regimens arguably provide the greatest likelihood for patients to reach new, lower LDL-C targets; however, efficacy and safety data of any adjunctive treatment, along with drug costs and patient adherence to treatment (partly related to complexity of the regimen) all need to be considered when determining the optimal regimen to achieve LDL-C goals in individual patients according to their baseline absolute cardiovascular risk, LDL-C level, and consensus LDL-C targets.


A two-compartment mechanochemical model of the roles of transforming growth factor β and tissue tension in dermal wound healing.
The repair of dermal tissue is a complex process of interconnected phenomena, where cellular, chemical and mechanical aspects all play a role, both in an autocrine and in a paracrine fashion. Recent experimental results have shown that transforming growth factor -β (TGFβ) and tissue mechanics play roles in regulating cell proliferation, differentiation and the production of extracellular materials. We have developed a 1D mathematical model that considers the interaction between the cellular, chemical and mechanical phenomena, allowing the combination of TGFβ and tissue stress to inform the activation of fibroblasts to myofibroblasts. Additionally, our model incorporates the observed feature of residual stress by considering the changing zero-stress state in the formulation for effective strain. Using this model, we predict that the continued presence of TGFβ in dermal wounds will produce contractures due to the persistence of myofibroblasts; in contrast, early elimination of TGFβ significantly reduces the myofibroblast numbers resulting in an increase in wound size. Similar results were obtained by varying the rate at which fibroblasts differentiate to myofibroblasts and by changing the myofibroblast apoptotic rate. Taken together, the implication is that elevated levels of myofibroblasts is the key factor behind wounds healing with excessive contraction, suggesting that clinical strategies which aim to reduce the myofibroblast density may reduce the appearance of contractures.


Mechanical comparison of 3 different clamp and 2 different rod types of a new veterinary internal fixation system, 4.5/5.5-mm VetFix.
To compare the gripping force of a standard clamp with click-on and T clamps of the 4.5/5.5-mm VetFix (AO Research Institute, Davos, Switzerland), mounted on smooth and roughened rods. In vitro mechanical study. Rods were mounted on a clamp-holding device. Each clamp type was tested on a materials-testing machine in groups of 6 specimens for torsional and axial load stability on smooth and roughened rods (total, 72 specimens). The variable evaluated was the discontinuity point (DP) as a measure for gliding resistance of the clamp on the rod. Means (+/-SD) were calculated for all groups separately. For statistical comparison, a multiple regression model was fitted with level of significance set at P =.05. The direction of torsion had a significant effect on DP for both asymmetric clamps (standard, click-on). In torsion and axial load, the roughened rod had significantly higher DP levels than the smooth rod for the standard clamp. Rods differed only in axial load for the T clamp, again favoring the roughened rod. The click-on clamp did not reach 10% of the values achieved by the other clamps, independent from the rods and loading conditions. Compared with the T clamp, standard clamp DP values were significantly higher in torsion on the roughened rod as well as in axial load on both rod types. The roughened rod with a standard clamp was mechanically superior. For the T clamp, the small loss of gripping force may be compensated for by the possibility of inserting 2 more screws. The roughened rod may enhance the bending, compressive, and torsional properties of the 4.5/5.5-mm VetFix system by reducing the risk of clamp gliding on the rod. The standard clamp is the clamp of choice, except for the metaphyseal or epiphyseal region, at which use of a T clamp may be indicated to increase the number of screws inserted at the end of the rod.


I let a patient down by failing to challenge a doctor's decision.
During a clinical placement on a busy medical ward, I was caring for a patient with a primary diagnosis of lower respiratory infection. I noticed the patient was becoming increasingly short of breath and had bilateral ankle oedema.


Venus: density of upper atmosphere from measurements of drag on pioneer orbiter.
Measurements of the changes in orbital period of the Pioneer Venus orbiter have yielded estimates of the density of the upper atmosphere of Venus at altitudes in the range from 150 to 200 kilometers. At the lower limit of this range, the density on the dayside of the terminator exhibits a temporal variation of amplitude near 4 x 10(-14) gram per cubic centimeter aboult a mean of approximately 1.4 x 10(-13) gram per cubic centimeter. The variation appears oscillatory, with a 4- to 5-day period, but barely one cycle was observed. The density on the nightside of the terminator, sampled inthe same 150-kilometer altitude range, fluctuates about a smaller mean of approximately 4 x 10(-14) gram per cubic centimeter. The density between the altitudes of 150 and 200 kilometers, sampled only on the dayside of the terminator, imply a scale height of between 15 and 20 kilometers. The interpretation of this estimate is uncertain, however, in view of the measurements at the different altitudes having been made at different times and, hence, at different values of solar phase.


Hip arthroscopy: patient assessment and indications.
Hip arthroscopy is often performed for disorders that in the past have gone unrecognized and untreated. The arthroscope has helped in the understanding of the nature of numerous intra-articular lesions, subsequently leading to improved assessment skills for these often elusive disorders, including interpretation of the history, examination findings, and technical advances in imaging studies. The indications for this procedure have been well defined but continue to evolve. Successful results from arthroscopy are most clearly linked to indications and proper patient selection.


[Study of atherogenic, coagulant and cardio-cerebral risk factors in the pathogenesis of minor strokes in arterial hypertension].
The paper is concerned with the results of studying risk factors correlations in patients who suffered minor brain stroke (MBS) associated with different forms of arterial hypertension (AH). As regards their importance in the pathogenesis of MBS, risk factors may be distributed into the two categories: atherogenic, coagulant and vascular alterations and ++cardio-cerebral ones characterizing the status of heart pump function. The atherogenic and coagulant risk factors (perivascular and intravascular lesions, agglutination of the capillaries by formed elements of the blood, aggregation of red blood cells, a high level of TH and beta-lipoproteins, fibrinogen and prothrombin) are significantly marked more widely and intensely among persons suffering from stable AH, with a history of MBS. Risk factors characterizing a decrease of heart pump function (myocardial contractility, ejection fractions) were demonstrable without significant differences among persons who suffered MBS associated with stable and labile AH. As to further studies, of the main interest is the pathogenesis of MBS in persons suffering from mild, episodic AH, since the data obtained may cast doubt on the thrombocoagulant mechanism thereof.


A handicap in Takotsubo cardiomyopathy: dynamic outflow obstruction.
Takotsubo cardiomyopathy (TCM) is an unusual form of acute cardiomyopathy showing left ventricular apical ballooning. Patients with hypotension should undergo urgent echocardiography to determine if left ventricular outflow tract (LVOT) obstruction is present. This complication has been described in 10-25% of all TCM patients. That some patients do not survive an acute TCM event underscores the importance of prompt recognition and targeted management of dynamic LVOT obstruction. Described in the present report is the case of a TCM patient with cardiogenic shock, the hemodynamics of which worsened after inotropic agents were administered, alleviated after serum fluid and beta-blocker treatment.


Interpretation of the Epigenetic Signature of Facioscapulohumeral Muscular Dystrophy in Light of Genotype-Phenotype Studies.
Facioscapulohumeral muscular dystrophy (FSHD) is characterized by incomplete penetrance and intra-familial clinical variability. The disease has been associated with the genetic and epigenetic features of the D4Z4 repetitive elements at 4q35. Recently, D4Z4 hypomethylation has been proposed as a reliable marker in the FSHD diagnosis. We exploited the Italian Registry for FSHD, in which FSHD families are classified using the Clinical Comprehensive Evaluation Form (CCEF). A total of 122 index cases showing a classical FSHD phenotype (CCEF, category A) and 110 relatives were selected to test with the receiver operating characteristic (ROC) curve, the diagnostic and predictive value of D4Z4 methylation. Moreover, we performed DNA methylation analysis in selected large families with reduced penetrance characterized by the co-presence of subjects carriers of one D4Z4 reduced allele with no signs of disease or presenting the classic FSHD clinical phenotype. We observed a wide variability in the D4Z4 methylation levels among index cases revealing no association with clinical manifestation or disease severity. By extending the analysis to family members, we revealed the low predictive value of D4Z4 methylation in detecting the affected condition. In view of the variability in D4Z4 methylation profiles observed in our large cohort, we conclude that D4Z4 methylation does not mirror the clinical expression of FSHD. We recommend that measurement of this epigenetic mark must be interpreted with caution in clinical practice.


Observing Localization in a 2D Quasicrystalline Optical Lattice.
Quasicrystals are long-range ordered but not periodic, representing an interesting middle ground between order and disorder. We experimentally and numerically study the localization transition in the ground state of noninteracting and weakly interacting bosons in an eightfold symmetric quasicrystalline optical lattice. In contrast to typically used real space in situ techniques, we probe the system in momentum space by recording matter wave diffraction patterns. Shallow lattices lead to extended states whereas we observe a localization transition at a critical lattice depth of V_{0}≈1.78(2)E_{rec} for the noninteracting system. Our measurements and Gross-Pitaevskii simulations demonstrate that in interacting systems the transition is shifted to deeper lattices, as expected from superfluid order counteracting localization. Quasiperiodic potentials, lacking conventional rare regions, provide the ideal testing ground to realize many-body localization in 2D.


Karyology: vaccine manufacturers' views.
Chromosomal analyses and life span studies of WI-38 cell cultures used for vaccine production at the Connaught Laboratories Ltd will be described. Twenty cultures derived from the same seed lot and 25 cultures derived from different starter cultures were analyzed. Karyology tests at population doublings 31 and higher were within acceptable limits. The WI-38 cells reached a finite lifespan of approximately 65 population doublings. Normal growth characteristics were observed within 2/3 of the finite lifespan, i.e. until population doubling 40. The finite lifespan of MRC-5 was found to be 75 population doublings, with normal growth pattern until passage 50. The karyology test results, cell yields and the finite lifespans indicated that these cells could be used as substrates for vaccine production at higher passage levels than previously suggested. Using serially subcultivated cells at higher passage levels would make possible an increase in the volume of vaccine from existing cell seed and would also result in significant reduction in production costs.