Diagnostic tools of early brain disturbances in an asymptomatic neonate with maple syrup urine disease.
Maple syrup urine disease (MSUD) is a rare inherited metabolic disorder resulting from the defective activity of branched-chain 2-ketoacid dehydrogenase complex. Routine screening of newborn with tandem mass spectroscopy on the third day of life may detect elevated branched-chain amino acids in blood before the appearance of encephalopathic symptoms in MSUD cases. If undiagnosed by such a routine screening test, patients often present with encephalopathy and seizures. Clinical neurologic examination is supplemented by electroencephalography and imaging. Here, we report abnormal amplitude-integrated electroencephalography, electroencephalography, magnetic resonance imaging, and magnetic resonance imaging spectroscopy findings in a neurologically asymptomatic male newborn who was diagnosed with MSUD at the third week of life. These neurologic disturbances disappeared at the fourth month of life with appropriate special diet. Therefore, even in already asymptomatic cases, early neurologic deterioration of brain metabolism and structure can be detected with these early laboratory findings, indicating the importance of early diagnosis and management. Patients may also benefit from these investigations during the follow-up period.


[Treatment of dystrophy, dysplasia and initial stages of vulvar carcinoma in virus infections].
Overall sixty-seven patients with distrophy, dysplasia and valvular carcinoma presenting with human papilloma virus- and herpes simplex-2 virus infections underwent a complex treatment intended for background, precancerous affections of the vulva and for valvular carcinoma, involving the use of antiviral drug preparations laferon, zovirax, lovir (both on the systemic and local basis), and an immunomodulator (decaris). Efficacy of the above treatment option has been shown to be 98.5%.


Human keratinocyte growth factor activity on proliferation and differentiation of human keratinocytes: differentiation response distinguishes KGF from EGF family.
Human keratinocyte growth factor (KGF) is an epithelial cell specific mitogen which is secreted by normal stromal fibroblasts. In the present studies, we demonstrate that KGF is as potent as EGF in stimulating proliferation of primary or secondary human keratinocytes in tissue culture. Exposure of KGF- or EGF-stimulated keratinocytes to 1.0 mM calcium, an inducer of differentiation, led to cessation of cell growth. However, immunologic analysis of early and late markers of terminal differentiation, K1 and filaggrin, respectively, revealed striking differences in keratinocytes propagated in the presence of these growth factors. With KGF, the differentiation response was associated with expression of both markers whereas their appearance was retarded or blocked by EGF. TGF alpha, which also interacts with the EGF receptor, gave a similar response to that observed with EGF. These findings functionally distinguish KGF from the EGF family and support the role of KGF in the normal proliferation and differentiation of human epithelial cells.


Maintaining Tumor Heterogeneity in Patient-Derived Tumor Xenografts.
Preclinical models often fail to capture the diverse heterogeneity of human malignancies and as such lack clinical predictive power. Patient-derived tumor xenografts (PDX) have emerged as a powerful technology: capable of retaining the molecular heterogeneity of their originating sample. However, heterogeneity within a tumor is governed by both cell-autonomous (e.g., genetic and epigenetic heterogeneity) and non-cell-autonomous (e.g., stromal heterogeneity) drivers. Although PDXs can largely recapitulate the polygenomic architecture of human tumors, they do not fully account for heterogeneity in the tumor microenvironment. Hence, these models have substantial utility in basic and translational research in cancer biology; however, study of stromal or immune drivers of malignant progression may be limited. Similarly, PDX models offer the ability to conduct patient-specific in vivo and ex vivo drug screens, but stromal contributions to treatment responses may be under-represented. This review discusses the sources and consequences of intratumor heterogeneity and how these are recapitulated in the PDX model. Limitations of the current generation of PDXs are discussed and strategies to improve several aspects of the model with respect to preserving heterogeneity are proposed.


Malnutrition in morbidly obese patients: fact or fiction?
Reports of nutritional deficiencies after Bariatric surgery have lead investigators to inquire about the preoperative nutritional status of morbidly obese patients. Interestingly, numerous reports demonstrated a pattern of low levels of various micronutrients among overweight and obese patients, even in comparison with normal weight population. In this article we reviewed the literature for micronutrient deficiencies in obese patients prior to weight reduction surgery.


[Spontaneous retroperitoneal hematoma. Report of one case].
Spontaneous retroperitoneal hematoma is a rare condition. We report a 78 year-old man with progressive pain in his right thigh and hip lasting one week. The pain subsequently was associated with abdominal pain in the right lower quadrant. Physical examination revealed pain to deep palpation of the area, associated with a diffuse positive rebound pain. An abdominal and pelvis CT scan showed an extensive mesenteric hematoma. During surgery, a large retroperitoneal encapsulated hematoma, without evidence of active bleeding, was found and drained. Pathology confirmed the diagnosis and was negative for cancer.


Metalloproteinase expression in monocytes and macrophages and its relationship to atherosclerotic plaque instability.
Matrix metalloproteinases (MMPs) can degrade strength-giving collagens and other structural proteins of the arterial extracellular matrix. Overproduction of MMPs by monocyte/macrophages could therefore promote atherosclerotic plaque rupture and myocardial infarction. Freshly-recruited monocyte macrophages appear to use a prostaglandin (PG)-dependent pathway to coordinately upregulate a broad and potentially highly-destructive spectrum of MMPs. Differentiated macrophages rely on a series of distinct pathways to selectively upregulate groups of MMPs. Moreover, recent evidence suggests that different macrophage phenotypes express characteristically different spectra of MMPs and their inhibitors. New therapies may result from targeting matrix MMP overproduction.


Comparison of methods: determination of UV protection of clothing.
Based on spectrophotometric measurements and mathematical calculations, the ultraviolet (UV) protection factor of a textile is determined in vitro. This technique is the most established test method for the determination of UV protection of a garment. However, the validity and practicality of the in vitro UV protection factor (UPF) determined in the laboratory has been a controversial issue with regard to its significance in the field. Several studies have verified the in vitro UPF by comparing it with various in vivo test protocols using solar-simulated radiation for the determination of the minimal erythema dose. The data inconsistency between these studies is certainly due to different methodology. Furthermore, UV dosimetry is a suitable method for quantifying UV transmission through a garment. Chemical dosimeters (e.g. polysulfone films) and biological UV detector films have been used in in vivo-simulated studies in the form of small portable badges monitoring solar UV transmittance through garments on manikins and mobile subjects. As sunlight consists to a considerable extent of diffuse radiation, which is more scattered and absorbed by the fabric than direct radiation, UPF values obtained by measurements in real exposure situations are usually higher than those obtained by conventional in vitro and in vivo testing with collimated radiation beams. Thus the discrepancy between laboratory-based testing and field-based measurements may be due to different radiation geometry of UV sources. Taken together, the in vitro method is the most practicable and inexpensive method for routine measurements of UPF, but dosimetry seems to be a highly useful method for determining the UPF in real exposure situations.


Optimum observation conditions of emission spectra from laser induced plasmas evaluated by using a two-dimensionally imaging spectrograph.
A two-dimensionally imaging spectrometer system was employed to measure spatial variations in the intensities of emission lines in a Cu-Mn-Ni alloy sample when they were excited from a laser-induced plasma with krypton gas. The emission zone of these lines shrank and had greater emission intensities with increasing gas pressure, and the intensities of their background also became more intense. It was thus found that the optimum observation zone for the analytical application varied with the pressure of the plasma gas. The two-dimensional distribution of the signal-to-background ratio for each analytical line was investigated to determine the measuring conditions for the emission analysis, indicating that the spatially-resolved measurement was generally superior to the conventional spatially-integrated measurement over the plasma region.


Intrapreoptic microinjection of GHRH or its antagonist alters sleep in rats.
Previous reports indicate that growth hormone-releasing hormone (GHRH) is involved in sleep regulation. The site of action mediating the nonrapid eye movement sleep (NREMS)-promoting effects of GHRH is not known, but it is independent from the pituitary. GHRH (0.001, 0. 01, and 0.1 nmol/kg) or a competitive antagonist of GHRH (0.003, 0.3, and 14 nmol/kg) was microinjected into the preoptic area, and the sleep-wake activity was recorded for 23 hr after injection in rats. GHRH elicited dose-dependent increases in the duration and in the intensity of NREMS compared with that in control records after intrapreoptic injection of physiological saline. The antagonist decreased the duration and intensity of NREMS and prolonged sleep latency. Consistent alterations in rapid eye movement sleep (REMS) and in brain temperature were not found. The GHRH antagonist also attenuated the enhancements in NREMS elicited by 3 hr of sleep deprivation. Histological verification of the injection sites showed that the majority of the effective injections were in the preoptic area and the diagonal band of Broca. The results indicate that the preoptic area mediates the sleep-promoting activity of GHRH.


Differential gene expression at gestational days 14 and 16 in normal and nitrogen-induced hypoplastic murine fetal lungs with coexistent diaphragmatic hernia.
The purpose of this study was to identify differentially expressed genes in normal and nitrofen-induced hypoplastic lungs in fetal mice. Such genes may play a role in the regulation of lung development. CD-1 pregnant dams were gavaged with 25 mg of nitrofen on gestational day (Gd) 8 to induce pulmonary hypoplasia and diaphragmatic hernia (DH). Normal and nitrofen-treated fetuses were removed on Gd 14 and Gd 16. Lungs were examined in all nitrofen-exposed fetuses and only those that had developed severely hypoplastic lungs with coexistent diaphragmatic hernia were taken for molecular analyses. RNA was extracted from normal and nitrofen-treated lungs, reverse transcribed, and PCR-amplified using 48 combinations of anchor and arbitrary primers for each condition. The resulting cDNAs from normal and hypoplastic lungs were run on 6% polyacrylamide differential display gels. In Gd 14 lungs, we observed 10 differentially expressed cDNA bands, of which 6 were identified to be inhibited and 4 were reduced in the hypoplastic lungs compared to normal fetal lungs. From the Gd 16 lungs, a total of 29 differentially expressed cDNA bands were found, of which 11 were reduced, 4 were inhibited, 11 were enhanced, and 3 were induced in the hypoplastic compared to the normal lungs. All 39 differentially expressed cDNAs were cloned, sequenced, and identified through BLAST searches. Among the sequences that were identified, results were as follows: 1) Hypoplastic Gd 14 lungs had two unknown cDNA sequences with reduced/inhibited expressions, whereas one was a known sequence having 77% similarity with a promoter region regulating various cytokines such as IL-1, IL-2, and IL-11. The expression of this sequence was inhibited in the hypoplastic lungs. This sequence also had similarity to lipid-binding proteins. 2) On Gd 16, hypoplastic lungs had one cDNA sequence with reduced expression which had 82% similarity with thyroid hormone receptor gene exon 1 and two other cDNA sequences with enhanced expressions. One of these enhanced cDNA sequences in hypoplastic lungs had 98% similarity with the fibroblast growth factor receptor-3 gene, and the other was an unknown sequence. Northern blot hybridizations were performed to confirm the differential expression of the two sequences of interest, which were identified as thyroid hormone receptor and fibroblast growth factor (FGF) receptor-3. Overall, out of a total of 39 RT-PCR products (i.e., cDNAs), the abundance of which was altered by nitrofen, 6 were found to be homologous to sequences in Gen Bank through BLAST searches. These 6 sequences became the products of interest, and 3 of these 6 products were similar to previously identified genes. Our results may shed some light on regulatory aspects of lung development and open avenues for treatment of hypoplastic lungs and other respiratory problems in human neonates.


Assessments of the quality systems of pharmaceutical distributors: a remote approach to be applied in times of COVID-19 and beyond.
Adequate quality systems throughout pharmaceutical supply chains are crucial to protect individuals and communities from substandard and falsified medical products. Thus, pharmaceutical distributors are regularly assessed by qualified experts. Since the COVID-19 pandemic has forced a suspension of normal activities, remote assessments via videoconferencing may represent a temporary alternative to on-site audits. We exploratorily evaluated the feasibility of remote assessments of pharmaceutical distributors, located in a low- or middle-income country hard-to reach during the COVID-19 pandemic. We conducted pilot remote assessments of four conveniently selected distributors. The expert was remotely connected via videoconference, and supported by an in-country assessment facilitator (ICAF), who had received ad hoc training and was present at the assessed facility. First, the remote expert assessed the quality assurance (QA) activities and rated their compliance with the standards of the World Health Organization Good Storage & Distribution Practices (GSDP), as per routine practice. Second, s/he assessed the completeness, clarity and accuracy of data collected remotely, first per distributor, and then in aggregated form. Data completeness was assessed by the expert as excellent, while clarity and accuracy were good. Overall data quality (a combination of completeness, clarity and accuracy) was good, with no major differences across QA activities, nor across distributors. Contextual limitations included poor internet connection, language barriers, and distributors' lack of familiarity with QA terminology. Our findings are exploratory and cannot be extrapolated to other contexts, nor to other types of audits. Nonetheless, this pilot experience suggests that a well-planned remote assessment of pharmaceutical distributors, conducted with the support of a well-trained onsite ICAF, can provide data of acceptable quality, allowing to assess GSDP-compliance and to make temporary decisions about licensing or purchasing. Purchasers and policy makers should read the results of remote assessments in light of their intrinsic limitations. At the moment, onsite assessments remain the gold standards, but this could change in the longer term, with improved information technology and in light of the need to avoid unnecessary travels. Furthermore, remote assessments could be considered for routine pre-screening candidates for on-site assessments, and for targeted follow-up of on-site assessment.


Reactions to Minor-Older and Minor-Peer Sex as a Function of Personal and Situational Variables in a Finnish Nationally Representative Student Sample.
Felson et al. (2019) used a large-scale nationally representative Finnish sample of sixth and ninth graders to estimate the population prevalence of negative subjective reactions to sexual experiences between minors under age 18 and persons at least 5 years older and between minors and peer-aged partners for comparison. They then accounted for these reactions in multivariate analysis based on contextual factors. The present study argued that focusing exclusively on negative reactions short-changed a fuller scientific understanding. It analyzed the full range of reactions in the same sample, focusing on positive reactions. For reactions in retrospect, boys frequently reacted positively to minor-older sex (68%, n = 280 cases), on par with positive reactions to boy-peer sex (67%, n = 1510). Girls reacted positively to minor-older sex less often (36%, n = 1047) and to girl-peer sex half the time (48%, n = 1931). In both minor-older and minor-peer sex, rates of positive reactions were higher for boys vs. girls, adolescents vs. children, when partners were friends vs. strangers or relatives, with intercourse vs. lesser forms of sexual intimacy, with more frequent sex, and when not coerced. Boys reacted positively more often with female than male partners. In minor-older sex, partner age difference mattered for girls but not boys, and the minor's initiating the sex (14% for girls, 46% for boys) produced equally high rates of positive reactions. Most of these factors remained significant in multivariate analysis. The frequency of positive reactions, their responsiveness to context, the similarity in reaction patterns with minor-peer sex, and the generalizability of the sample were argued to contradict the trauma view often applied to minor-older sex, holding it to be intrinsically aversive irrespective of context.


Injuries and poisonings associated with methamphetamine use: sentinel surveillance, the electronic Canadian Hospitals Injury Reporting and Prevention Program (eCHIRPP), 2011-2019.
Information from emergency department (ED) visits for methamphetamine-related injuries and poisonings between 1 April 2011 and 9 August 2019 were captured from 19 sentinel sites across Canada for all ages. Overall, 1093 cases (97.6/100 000 eCHIRPP cases) were identified (59.4% male), with female patients experiencing more poisonings (71% vs 57.4% for males). Unintentional injuries and poisoning accounted for 14.8% of ED presentations. Self-harm (while or as a result of consuming methamphetamine) accounted for 11.4% of cases. The circumstances surrounding injuries and poisonings associated with methamphetamine are varied and include self-harm, fall-related brain injuries, mental illness, criminal activity and other circumstances. These domains should be taken into account when developing mitigation strategies.


Multispectral optoacoustic tomography of muscle perfusion and oxygenation under arterial and venous occlusion: A human pilot study.
Perfusion and oxygenation are critical parameters of muscle metabolism in health and disease. They have been both the target of many studies, in particular using near-infrared spectroscopy (NIRS). However, difficulties with quantifying NIRS signals have limited a wide dissemination of the method to the clinics. Our aim was to investigate whether clinical multispectral optoacoustic tomography (MSOT) could enable the label-free imaging of muscle perfusion and oxygenation under clinically relevant challenges: the arterial and venous occlusion. We employed a hybrid clinical MSOT/ultrasound system equipped with a hand-held scanning probe to visualize hemodynamic and oxygenation changes in skeletal muscle under arterial and venous occlusions. Four (N = 4) healthy volunteers were scanned over the forearm for both 3-minute occlusion challenges. MSOT-recorded pathophysiologically expected results during tests of disturbed blood flow with high resolution and without the need for contrast agents. During arterial occlusion, MSOT-extracted Hb-values showed an increase, while HbO2 - and total blood volume (TBV)-values remained roughly steady, followed by a discrete increase during the hyperemic period after cuff deflation. During venous occlusion, results showed a clear increase in intramuscular HbO2 , Hb and TBV within the segmented muscle area. MSOT was found to be capable of label-free non-invasive imaging of muscle hemodynamics and oxygenation under arterial and venous occlusion. We introduce herein MSOT as a novel modality for the assessment of vascular disorders characterized by disturbed blood flow, such as acute limb ischemia and venous thrombosis.


Prevalence and characterization of quinolone resistance mechanisms in commensal Escherichia coli isolated from slaughter animals in Poland, 2009-2012.
The background of quinolone resistance was characterized in ciprofloxacin-resistant commensal Escherichia coli selected out of 3,551 isolates from slaughtered animals in Poland between 2009 and 2012. Plasmid-mediated determinants were suspected in 6.2% of the study group, ranging from 1.1% in cattle to 9.7% in turkeys. Polymerase chain reaction and sequencing identified up to four quinolone resistance-determining substitutions in gyrA (Ser83, Asp87) and parC (Ala56, Ser80). Plasmid-mediated mechanisms were identified as qnrS1 (or qnrS3, n=70, including six isolates with chromosomal mutations), qnrB19 (or qnrB10, n=19), and qnrB17 (n=1). All tested isolates were negative for qnrA, qnrC, qnrD, qepA, and aac(6')-Ib-cr. Still, there were several E. coli suspected for both plasmid- and chromosome-mediated resistance with unrevealed genetic background of the phenomenon. Since all tested isolates showed diverse XbaI-PFGE profiles, chromosome-encoded quinolone resistance does not result from the spread of a single resistant clone, however, it is rather due to antimicrobial pressure leading to the selection of random gyr and par mutants. It also favors the selection and spread of plasmids carrying predominant qnr genes, since the same determinants were found in Salmonella, isolated from similar sources. The identification of carrier plasmids and mitigation of their spread might be essential for sustainable quinolone usage in animal husbandry and efficient protection of human health.


Antibody responses among adolescent females receiving the quadrivalent HPV vaccine series corresponding to standard or non-standard dosing intervals.
Quadrivalent human papillomavirus vaccine (HPV4) is recommended as a 3-dose series administered at 0, 1-2, and 6 months. However, this dosing schedule is often not followed leading to longer dosing intervals. We conducted a prospective study to assess antibody titers to HPV4 when dose 2 and/or dose 3 were administered on schedule or delayed. Healthy females (N=331) aged 9-18 years were enrolled at the time of receipt of HPV4 dose 2 or 3. Participants were classified as belonging to one of four groups depending upon timing of receipt of HPV4: both doses on time; only dose 2 delayed later than 90 days; only dose 3 delayed later than 180 days; or both doses 2 and 3 delayed. Pre- and post-dose 3 blood samples were assayed for HPV antibody titers (types 6, 11, 16, and 18). Post-dose 3 geometric mean titers (GMTs) for all HPV types were not significantly lower for any of the delayed dosing groups when compared to the on time group. When compared to the on time group, the post dose 3 GMTs in the delayed dose 3 group were significantly higher (p<0.05) for HPV types 6, 11, and 16. Our findings suggest that delays of dose 2 or 3 do not interfere with immune responses after completion of the 3-dose series. These results support current recommendations to not administer additional doses of HPV4 vaccine if dose 2, dose 3, or both doses have been administered late.


Advances in colon cancer chemotheapy: nursing implications.
Adjuvant chemotherapy for colon cancer has changed significantly during the past 5 years. The traditional agent fluorouracil has been joined by new drugs, including capecitabine, irinotecan, oxaliplatin, and targeted agents such as bevacizumab and cetuximab. These new agents bring different mechanisms of action, different side effects, and new home care nursing implications. Significant improvements in disease-free remissions and survival rates are among the many benefits of these therapies to persons with colon cancer. This article covers these newer agents, targeted therapies for colon cancer, and associated nursing and patient implications, including detailed drug information.


Measuring coping style and resistance among Spanish and Argentine samples: development of the Systematic Treatment Selection Self-Report in Spanish.
This article reports the reliability and validity of the Coping Style and Resistance subscales of the Systematic Treatment Selection Self-Report (STS-SR) scale after its translation to Spanish. The English versions of the STS system identify eight empirically derived patient variables that have been found to moderate the effects of various classes of mental health treatment procedures. Research on these dimensions as treatment indicators, as assessed both by clinicians and through patient self-reports, indicates that they increase the efficiency and effectiveness of treatment among English-speaking samples. This article reports a study of the convergent and discriminant validity of two of the subscales, Coping Style and Trait Resistance. The subscales were translated English into Spanish and administered to large Spanish and Argentine subject pools, along with established measures of the same and related constructs. Results revealed that both scales possessed good internal consistency and adequate discriminant validity. The implications of these findings are discussed.


Direct imaging of bridged twin protoplanetary disks in a young multiple star.
Studies of the structure and evolution of protoplanetary disks are important for understanding star and planet formation. Here we present the direct image of an interacting binary protoplanetary system. Both circumprimary and circumsecondary disks are resolved in the near-infrared. There is a bridge of infrared emission connecting the two disks and a long spiral arm extending from the circumprimary disk. Numerical simulations show that the bridge corresponds to gas flow and a shock wave caused by the collision of gas rotating around the primary and secondary stars. Fresh material streams along the spiral arm, consistent with the theoretical scenarios in which gas is replenished from a circummultiple reservoir.


Revision total knee arthroplasty for flexion instability : a concise follow-up of a previous report.
We have previously reported the mid-term outcomes of revision total knee arthroplasty (TKA) for flexion instability. At a mean of four years, there were no re-revisions for instability. The aim of this study was to report the implant survivorship and clinical and radiological outcomes of the same cohort of of patients at a mean follow-up of ten years. The original publication included 60 revision TKAs in 60 patients which were undertaken between 2000 and 2010. The mean age of the patients at the time of revision TKA was 65 years, and 33 (55%) were female. Since that time, 21 patients died, leaving 39 patients (65%) available for analysis. The cumulative incidence of any re-revision with death as a competing risk was calculated. Knee Society Scores (KSSs) were also recorded, and updated radiographs were reviewed. The cumulative incidence of any re-revision was 13% at a mean of ten years. At the most recent-follow-up, eight TKAs had been re-revised: three for recurrent flexion instability (two fully revised to varus-valgus constrained implants (VVCs), and one posterior-stabilized (PS) implant converted to VVC, one for global instability (PS to VVC), two for aseptic loosening of the femoral component, and two for periprosthetic joint infection). The ten-year cumulative incidence of any re-revision for instability was 7%. The median KSS improved significantly from 45 (interquartile range (IQR) 40 to 50) preoperatively to 70 (IQR 45 to 80) at a mean follow-up of ten years (p = 0.031). Radiologically, two patients, who had not undergone revision, had evidence of loosening (one tibial and one patellar). The remaining components were well fixed. We found fair functional outcomes and implant survivorship at a mean of ten years after revision TKA for flexion instability with a PS implant. Recurrent instability and aseptic loosening were the most common indications for re-revision. Components with increased constraint, such as a VVC or hinged, should be used in these patients in order to reduce the risk of recurrent instability.Cite this article: Bone Joint J 2022;104-B(10):1126-1131.


Active cytoskeletal composites display emergent tunable contractility and restructuring.
The cytoskeleton is a model active matter system that controls processes as diverse as cell motility and mechanosensing. While both active actomyosin dynamics and actin-microtubule interactions are key to the cytoskeleton's versatility and adaptability, an understanding of their interplay is lacking. Here, we couple microscale experiments with mechanistic modeling to elucidate how connectivity, rigidity, and force-generation affect emergent material properties in composite networks of actin, tubulin, and myosin. We use multi-spectral imaging, time-resolved differential dynamic microscopy and spatial image autocorrelation to show that ballistic contraction occurs in composites with sufficient flexibility and motor density, but that a critical fraction of microtubules is necessary to sustain controlled dynamics. The active double-network models we develop, which recapitulate our experimental findings, reveal that while percolated actomyosin networks are essential for contraction, only composites with comparable actin and microtubule densities can simultaneously resist mechanical stresses while supporting substantial restructuring. The comprehensive phase map we present not only provides important insight into the different routes the cytoskeleton can use to alter its dynamics and structure, but also serves as a much-needed blueprint for designing cytoskeleton-inspired materials that couple tunability with resilience and adaptability for diverse applications ranging from wound healing to soft robotics.


The Spemann organizer of Xenopus is patterned along its anteroposterior axis at the earliest gastrula stage.
The Spemann organizer is largely responsible for organizing and patterning the anteroposterior axis during the development of amphibians. In this report, we examine the degree of anteroposterior pattern in the earliest gastrula organizer of Xenopus using a combination of embryological and molecular techniques. When we divide the earliest gastrula organizer, a region measuring 20 cells high by 25 cells wide, into stereotyped anterior (vegetal) and posterior (animal) halves, each half not only has a distinct fate and state of specification, but also induces a unique set of region-specific neural genes. When wrapped in animal cap ectoderm, the anterior half induces only anterior-specific genes (XAG-1 and otxA), while the posterior half induces anterior (otxA and reduced levels of XAG-1) and posterior (Hox B9) neural genes, revealing early localization of neural posteriorizing activity to posterior mesendoderm. This is the earliest demonstration of regionalized neural induction by the Xenopus organizer. Additionally, based on the expression of gsc, Xbra, and Xnot, we show that the organizer is patterned both at the early gastrula stage and prior to the appearance of bottle cells.


Lipofilling effects after breast cancer surgery in post-radiation patients: an analysis of results and algorithm proposal.
Lipofilling or autologous fat transfer is an established technique in plastic surgery. Herein, we describe the lipofilling effects after implant-based breast reconstruction in post-radiation patients and propose an algorithm for indication of lipofilling. Forty patients with a history of breast cancer were included in this retrospective analysis. Patients had undergone either breast conserving therapy or mastectomy. Twenty-six patients underwent additional radiation therapy. Patients were assessed using a post-radiation skin scoring classification. In total, 68 lipofilling procedures were analyzed. Scar release, skin softening, improved quality of life, and improvement of post-radiation findings are results of lipofilling with a closed filtration system. In all patients with post-surgical radiation, an improvement of tissue quality was observed. Staging revealed that lipofilling improved mean post-radiation skin scores of 2.40 ± 0.89 to 1.21 ± 0.76 (p ≤ 0.000). There was no recurrence of breast cancer in our study patients. This study introduces an algorithm using lipofilling in reconstructive breast surgery and especially in post-radiation patients with low risks as well as very high acceptance in patients with various indications for this procedure. A regenerative aspect was also detectable in patients following radiation therapy and reconstruction. Lipofilling is a safe and effective procedure with a low incidence of minor complications. It is therefore a feasible method to resolve volume deficiencies and asymmetric results after oncologic breast surgery. Nevertheless, a prospective study has now been initiated focusing on the oncologic safety of lipofilling including ultrasound and radiological examinations to validate the findings of this initial study. Level of Evidence: Level IV, therapeutic study.


Social normative origins of the taboo gap and implications for adolescent risk for HIV infection in Zambia.
Zambian Demographic and Health Survey data reveal that increased discordance between professed attitudes and measures of behaviour regarding premarital sex among adults is strongly associated with increased risk of HIV in adolescents, particularly girls. We hypothesised that this was due to the reluctance to talk about premarital sex, resulting in a situation we call the "taboo gap" where sexual behaviour is a forbidden topic and adolescents feel unable to seek advice or sexual and reproductive health services. Our analysis revealed that the taboo gap is rooted in harmful gender norms that are perpetuated by schools, churches, cultural influences, development programmes and health systems. Challenges like food insecurity and household poverty may place girls in positions where they are vulnerable to sexual exploitation, increasing their risk of exposure to HIV. Unmarried adolescents, particularly girls, report being ridiculed when they go to reproductive health clinics, which discourages them from seeking care in the future. Strengthening peer support and parent-child interactions are important programmatic elements. We conclude that discordance serves as a novel measure and harbinger for the presence of gender norms which generated a taboo gap that impeded carseeking and increased risk for HIV among adolescents, especially girls, in Zambia. We propose that successful interventions must involve a multifaceted, gender transformative approach which engages peers and stakeholders in schools, churches, clinics, and families, particularly parents, to reduce the gendered gap in HIV risk and transmission.


The Biological Variability of Plasma Ceramides in Healthy Subjects.
Ceramides are bioactive lipid species that mediate numerous cell-signaling events. Elevated plasma ceramides concentration constitutes a risk factor for several pathologies. Multiple studies have affirmed the plasma concentrations of 4 specific ceramides (Cer16:0, Cer18:0, Cer24:0, and Cer24:1) can predict cardiovascular disease risk. Furthermore, these ceramides can be altered by many lipid-lowering therapies. Understanding the biological variability within an individual, and within a population, will further inform the clinical use of plasma ceramides as a biomarker. In this study, we aimed to define the intra- and interbiological variability of ceramides in a healthy reference population in a weekly and monthly manner. Fasting plasma from 24 healthy adults was collected daily (5 days), weekly (4 weeks), and monthly (7 months). Ceramide concentrations were measured with liquid chromatography-mass spectrometry (LC-MS). For analysis, we used random-effects regression models to estimate variance components. The analytical variability was smaller compared to the biological variability overall. The greatest variation reported was between-subject variation for all ceramide species. The critical difference-reference change value (RCV) for within-subject variations monthly were 0.07 mcmol/L (Cer16:0), 0.04 mcmol/L (Cer18:0), 1.09 mcmol/L (Cer24:0), and 0.27 mcmol/L (Cer24:1). The index of individuality (IOI) of ceramides were 0.82 (Cer16:0), 0.96 (Cer18:0), 1.06 (Cer24:0), and 0.89 (Cer24:1). The most consistent ceramide species was Cer18:0 with the lowest within- and between-subject critical differences in weekly and monthly measurements. Overall, this study demonstrates that the variability of ceramide concentrations at different time points is minimal within individuals, allowing a single draw to be sufficient at least in a yearly time frame.


Postradiation dental extractions without hyperbaric oxygen.
This study examined the incidence of osteoradionecrosis after tooth extraction with low-epinephrine or epinephrine-free, nonlidocaine local anesthetics and conservative surgical techniques. Estimates of the absorbed radiation dose on irradiated alveolar bone were made by reviewing radiotherapy records. This investigation included 72 patients ranging in age from 22 to 80 years (median 57.4 years). We removed 449 teeth. Analysis of radiotherapy check films revealed that only 196 teeth (44%) were included within the treatment volume. The median prescribed tumor dose was 50 Gy (range 25 to 84 Gy) in 20 fractions (range 10 to 37), with a median dose per fraction of 2.5 Gy (range 1.88 to 3.14 Gy). Follow-up time ranged from 68 days to 19.3 years (median 4.8 years). No instances of osteoradionecrosis occurred as a result of dental extraction with this conservative method.


The Spanish Influenza Pandemic: a lesson from history 100 years after 1918.
In Europe in 1918, influenza spread through Spain, France, Great Britain and Italy, causing havoc with military operations during the First World War. The influenza pandemic of 1918 killed more than 50 million people worldwide. In addition, its socioeconomic consequences were huge. "Spanish flu", as the infection was dubbed, hit different age-groups, displaying a so-called "W-trend", typically with two spikes in children and the elderly. However, healthy young adults were also affected. In order to avoid alarming the public, several local health authorities refused to reveal the numbers of people affected and deaths. Consequently, it was very difficult to assess the impact of the disease at the time. Although official communications issued by health authorities worldwide expressed certainty about the etiology of the infection, in laboratories it was not always possible to isolate the famous Pfeiffer's bacillus, which was, at that time, deemed to be the cause of influenza. The first official preventive actions were implemented in August 1918; these included the obligatory notification of suspected cases and the surveillance of communities such as day-schools, boarding schools and barracks. Identifying suspected cases through surveillance, and voluntary and/or mandatory quarantine or isolation, enabled the spread of Spanish flu to be curbed. At that time, these public health measures were the only effective weapons against the disease, as no vaccines or antivirals were available. Virological and bacteriological analysis of preserved samples from infected soldiers and other young people who died during the pandemic period is a major step toward a better understanding of this pandemic and of how to prepare for future pandemics.


Primary cardiac angiosarcoma associated with cardiac tamponade: case report.
A 57-year-old male with primary cardiac angiosarcoma was initially admitted for cardiac tamponade. Pericardiocentesis was performed twice preoperatively, but the bloody pericardial fluid was cytologically negative for malignant cells. The tumor in the right atrium was resected during cardiopulmonary bypass. The resected tumor was 5.5x4.5x3.0cm in size and the diagnosis of cardiac angiosarcoma was made histologically. There were no tumor cells in the surgical margin. Unfortunately the patient died 3.5 months after surgery due to multiple recurrence in the pericardium. A suitable therapy for cardiac angiosarcoma is still controversial, but early antemortem diagnosis and more aggressive combined treatment should be considered.


Association Between Hospital Private Equity Acquisition and Outcomes of Acute Medical Conditions Among Medicare Beneficiaries.
As private equity (PE) acquisitions of short-term acute care hospitals (ACHs) continue, their impact on the care of medically vulnerable older adults remains largely unexplored. To investigate the association between PE acquisition of ACHs and access to care, patient outcomes, and spending among Medicare beneficiaries hospitalized with acute medical conditions. This cross-sectional study used a generalized difference-in-differences approach to compare 21 091 222 patients admitted to PE-acquired vs non-PE-acquired short-term ACHs between January 1, 2001, and December 31, 2018, at least 3 years before to 3 years after PE acquisition. The analysis was conducted between December 28, 2020, and February 1, 2022. Differences were estimated using both facility and hospital service area fixed effects. To assess the robustness of findings, regressions were reestimated after including fixed effects of patient county of origin to account for geographic differences in underlying health risks. Two subset analyses were also conducted: (1) an analysis including only hospitals in hospital referral regions with at least 1 PE acquisition and (2) an analysis stratified by participation in the Hospital Corporation of America 2006 acquisition. The study included Medicare beneficiaries 66 years and older who were hospitalized with 1 of 5 acute medical conditions: acute myocardial infarction (AMI), acute stroke, chronic obstructive pulmonary disease exacerbation, congestive heart failure exacerbation, and pneumonia. Acquisition of hospitals by PE firms. Comorbidity burden (measured by Elixhauser comorbidity score), hospital length of stay, in-hospital mortality, 30-day mortality, 30-day readmission, and 30-day episode payments. Among 21 091 222 total Medicare beneficiaries admitted to ACHs between 2001 and 2018, 20 431 486 patients received care at non-PE-acquired hospitals, and 659 736 received care at PE-acquired hospitals. Across all admissions, the mean (SD) age was 79.45 (7.95) years; 11 727 439 patients (55.6%) were male, and 4 550 012 patients (21.6%) had dual insurance; 2 996 560 (14.2%) patients were members of racial or ethnic minority groups, including 2 085 128 [9.9%] Black and 371 648 [1.8%] Hispanic; 18 094 662 patients (85.8%) were White. Overall, 3 083 760 patients (14.6%) were hospitalized with AMI, 2 835 777 (13.4%) with acute stroke, 3 674 477 (17.4%) with chronic obstructive pulmonary disease exacerbation, 5 868 034 (27.8%) with congestive heart failure exacerbation, and 5 629 174 (26.7%) with pneumonia. Comorbidity burden decreased slightly among patients admitted with acute stroke (difference, -0.04 SDs; 95% CI, -0.004 to -0.07 SDs) at acquired hospitals compared with nonacquired hospitals but was unchanged across the other 4 conditions. Among patients with AMI, a greater decrease in in-hospital mortality was observed in PE-acquired hospitals compared with non-PE-acquired hospitals (difference, -1.14 percentage points, 95% CI, -1.86 to -0.42 percentage points). In addition, a greater decrease in 30-day mortality (difference, -1.41 percentage points; 95% CI, -2.26 to -0.56 percentage points) was found at acquired vs nonacquired hospitals. However, 30-day spending and readmission rates remained unchanged across all conditions. The extent and directionality of estimates were preserved across all robustness assessments and subset analyses. In this cross-sectional study using a difference-in-differences approach, PE acquisition had no substantial association with the patient-level outcomes examined, although it was associated with a moderate improvement in mortality among Medicare beneficiaries hospitalized with AMI.


Antiretroviral drug susceptibility among HIV-infected adults failing antiretroviral therapy in Rakai, Uganda.
We analyzed antiretroviral drug susceptibility in HIV-infected adults failing first- and second-line antiretroviral treatment (ART) in Rakai, Uganda. Samples obtained from participants at baseline (pretreatment) and at the time of failure on first-line ART and second-line ART were analyzed using genotypic and phenotypic assays for antiretroviral drug resistance. Test results were obtained from 73 samples from 38 individuals (31 baseline samples, 36 first-line failure samples, and six second-line failure samples). Four (13%) of the 31 baseline samples had mutations associated with resistance to nucleoside or nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs, respectively). Among the 36 first-line failure samples, 31 (86%) had NNRTI resistance mutations and 29 (81%) had lamivudine resistance mutations; only eight (22%) had other NRTI resistance mutations. None of the six individuals failing a second-line protease inhibitor (PI)-based regimen had PI resistance mutations. Six (16%) of the participants had discordant genotypic and phenotypic test results. Genotypic resistance to drugs included in first-line ART regimens was detected prior to treatment and among participants failing first-line ART. PI resistance was not detected in individuals failing second-line ART. Surveillance for transmitted and acquired drug resistance remains a priority for scale-up of ART.


Risks associated with use of stimulant medications in patients with obstructive sleep apnea and cardiomyopathy: a case-control study.
Stimulant medications are indicated in patients with obstructive sleep apnea (OSA) who experience sleepiness despite optimal control of sleep-disordered breathing. The safety of stimulant medications in patients with OSA and co-morbid cardiomyopathy is unknown. We performed a case-control study to assess cardiovascular outcomes and mortality risk associated with stimulant use in this group of patients. A total of 162 subjects with OSA and cardiomyopathy were identified. Subjects who used stimulant medications for ≥1 month were designated as cases. Age-and-sex-matched controls not taking these medications were randomly chosen from the same cohort. Outcomes assessed were mortality, implantable cardioverter-defibrillator (ICD) and pacemaker insertion. Twenty-two cases and 44 controls were included in the analyses. Mean age was 62.6 ± 15 years, 72% were male. Median duration of medication use was 27 months (range 1-98). There were four deaths among cases versus eight among controls. Four cases had a pacemaker and six had an ICD inserted, compared to six and eight respectively in the control group. Age (p = 0.01) and positive airway pressure (PAP) compliance (p = 0.01), but not stimulant medication use (p = 1.00) were associated with mortality on univariate analysis. In multiple logistic regression analyses accounting for body mass index, apnea-hypopnea index/respiratory disturbance index, PAP compliance, ejection fraction and duration of follow up, use of stimulant medication was not associated with mortality (p = 0.50), pacemaker (p = 0.20) or ICD (p = 0.90) implantation. Stimulant medications were not associated with elevated risk of mortality, pacemaker or ICD implantation in this case-control study, even after accounting for multiple confounders.


The spectrum of double-outlet right atrium including hearts with three atrioventricular valves.
Double-outlet right atrium (DORA) is characterized by simultaneous right atrial emptying into both ventricles. Ventriculoatrial septal malalignment is the cardinal morphological feature. Three cases are presented to depict two major types of DORA-DORA with a malaligned atrial septum and DORA with a malaligned ventricular septum. We describe two subtypes of each form of DORA: DORA with a malaligned atrial septum presents with either a common atrioventricular (AV) junction (guarded by a common AV valve) or with a single AV junction (due to the absence of the left AV junction). DORA with a malaligned ventricular septum may be associated with a right ventricle (RV) that is adequate for biventricular repair or a severely hypoplastic RV not compatible with biventricular repair. DORA with a malaligned ventricular septum is closely related to typical straddling of the tricuspid valve. Peculiarly, DORA with a malaligned ventricular septum presents three AV valves at the AV junction and is associated with an abnormal disposition of the AV conduction axis. Clear understanding of the morphology of these lesions is important in preventing a surgical misadventure at the crux of the heart.


Nitrate assimilation in chicory roots (Cichorium intybus L.) which acquire radial growth.
Nitrate assimilation was analysed in chicory plants (Cichorium intybus L. cv. Turbo) during the early vegetative growth. Nitrate reductase (NR, EC 220.127.116.11) activity (NRA) was measured in roots and leaves at different developmental stages. During phase I, which corresponds to the structural growth (21-42 DAS), nitrate reduction mainly occurred in the roots. At the onset of the tuber formation (phase II), which is characterized by the formation of a cambium inducing a radial growth (42-63 DAS), NRA rapidly decreased in roots and developed in leaves. A tight correlation was found between the nitrate content, the amino acid level and NRA in roots and leaves. Northern blot and ELISA analysis showed that both levels of NR mRNA and NR protein were not modified during the time-course of the experiment suggesting that modification of nitrate assimilation was not controlled at a transcriptional level. In vitro NRA assayed in presence of either Mg2+ ions or EDTA showed that NR was influenced at least in part by a reversible phosphorylation/dephosphorylation reaction. Okadaic acid, a serine-threonine protein phosphatases inhibitor, strongly decreased NRA. Conversely, staurosporine, a serine-threonine protein kinases inhibitor, did not significantly change NRA in roots or leaves. Therefore, NRA was regulated at a post-translational level during the early vegetative growth by modifying the phosphorylation balance of the NR protein in chicory.


Bullying behaviors among US youth: prevalence and association with psychosocial adjustment.
Although violence among US youth is a current major concern, bullying is infrequently addressed and no national data on the prevalence of bullying are available. To measure the prevalence of bullying behaviors among US youth and to determine the association of bullying and being bullied with indicators of psychosocial adjustment, including problem behavior, school adjustment, social/emotional adjustment, and parenting. Analysis of data from a representative sample of 15 686 students in grades 6 through 10 in public and private schools throughout the United States who completed the World Health Organization's Health Behaviour in School-aged Children survey during the spring of 1998. Self-report of involvement in bullying and being bullied by others. A total of 29.9% of the sample reported moderate or frequent involvement in bullying, as a bully (13.0%), one who was bullied (10.6%), or both (6.3%). Males were more likely than females to be both perpetrators and targets of bullying. The frequency of bullying was higher among 6th- through 8th-grade students than among 9th- and 10th-grade students. Perpetrating and experiencing bullying were associated with poorer psychosocial adjustment (P<.001); however, different patterns of association occurred among bullies, those bullied, and those who both bullied others and were bullied themselves. The prevalence of bullying among US youth is substantial. Given the concurrent behavioral and emotional difficulties associated with bullying, as well as the potential long-term negative outcomes for these youth, the issue of bullying merits serious attention, both for future research and preventive intervention.


Sugarcane stem node identification algorithm based on improved YOLOv5.
Identification of sugarcane stem nodes is generally dependent on high-performance recognition equipment in sugarcane seed pre-cutting machines and inefficient. Accordingly, this study proposes a novel lightweight architecture for the detection of sugarcane stem nodes based on the YOLOv5 framework, named G-YOLOv5s-SS. Firstly, the study removes the CBS and C3 structures at the end of the backbone network to fully utilize shallow-level feature information. This enhances the detection performance of sugarcane stem nodes. Simultaneously, it eliminates the 32 times down-sampled branches in the neck structure and the 20x20 detection heads at the prediction end, reducing model complexity. Secondly, a Ghost lightweight module is introduced to replace the conventional convolution module in the BottleNeck structure, further reducing the model's complexity. Finally, the study incorporates the SimAM attention mechanism to enhance the extraction of sugarcane stem node features without introducing additional parameters. This improvement aims to enhance recognition accuracy, compensating for any loss in precision due to lightweight modifications. The experimental results showed that the average precision of the improved network for sugarcane stem node identification reached 97.6%, which was 0.6% higher than that of the YOLOv5 baseline network. Meanwhile, a model size of 2.6MB, 1,129,340 parameters, and 7.2G FLOPs, representing respective reductions of 82%, 84%, and 54.4%. Compared with mainstream one-stage target detection algorithms such as YOLOv4-tiny, YOLOv4, YOLOv5n, YOLOv6n, YOLOv6s, YOLOv7-tiny, and YOLOv7, G-YOLOv5s-SS achieved respective average precision improvements of 12.9%, 5.07%, 3.6%, 2.1%, 1.2%, 3%, and 0.4% in sugarcane stem nodes recognition. Meanwhile, the model size was compressed by 88.9%, 98.9%, 33.3%, 72%, 92.9%, 78.8% and 96.3%, respectively. Compared with similar studies, G-YOLOv5s-SS not only enhanced recognition accuracy but also considered model size, demonstrating an overall excellent performance that aligns with the requirements of sugarcane seed pre-cutting machines.


Urinary Lipid Peroxidation Byproducts: Are They Relevant for Predicting Neonatal Morbidity in Preterm Infants?
Preterm infants have an immature antioxidant system; however, they frequently require supplemental oxygen. Oxygen-free radicals cause both pulmonary and systemic inflammation, and they are associated with increased morbidity and mortality. Consequently, screening of metabolite profiles representing the amount of lipid peroxidation is considered of great relevance for the evaluation of in vivo oxidative stress and derived inflammation and damage. Ranges for total relative contents of isoprostanes (IsoPs), isofurans (IsoFs), neuroprostanes (NeuroPs), and neurofurans (NeuroFs) within targeted SpO2 ranges were determined in urine samples of 254 preterm infants<32 weeks of gestation within the frame of two randomized, controlled, and blinded clinical trials employing ultra-performance liquid chromatography-tandem mass spectrometry. A total of 536 serial urine samples collected during the first 4 weeks after birth in recruited infants who did not develop free radical associated conditions were analyzed. A reference range for lipid peroxidation byproducts, including isoprostanes, isofurans, neuroprostanes, and neurofurans, was calculated and possible correlations with neonatal conditions were investigated. Urinary elimination of isofurans in the first 4 days after birth correlated with later development of bronchopulmonary dysplasia. Our observations lead to the hypothesis that early urinary determination of lipid peroxidation byproducts, especially isofurans, is relevant to predict development of chronic lung conditions.


Catastrophizing and poor sleep quality in early adolescent females.
Catastrophizing about sleeplessness has been investigated in adults and children, but little is known about adolescents. This article aimed to (a) investigate whether early adolescent girls catastrophized about consequences of sleeplessness, (b) describe topics in catastrophizing sequences, (c) examine the association between sleep quality and catastrophizing, and (d) assess whether puberty moderated this association. Girls (n = 115) between 11 and 12 years old completed adapted versions of the Pittsburgh Sleep Quality Index, the Pubertal Developmental Scale, and the Catastrophizing Interview. Twenty-four (21%) participants produced catastrophizing sequences, including concerns about school and mood. Sleep quality was associated with catastrophizing (β = 0.19, p = .042); however, puberty did not moderate this association (β = 0.15, p = .126). Findings highlight the importance of sleep-related cognitions in adolescent girls.


Drivers of Emergency Department Use Among Oncology Patients in the Era of Novel Cancer Therapeutics: A Systematic Review.
Patients diagnosed with cancer are frequent users of the emergency department (ED). While many visits are unavoidable, a significant portion may be potentially preventable ED visits (PPEDs). Cancer treatments have greatly advanced, whereby patients may present with unique toxicities from targeted therapies and are often living longer with advanced disease. Prior work focused on patients undergoing cytotoxic chemotherapy, and often excluded those on supportive care alone. Other contributors to ED visits in oncology, such as patient-level variables, are less well-established. Finally, prior studies focused on ED diagnoses to describe trends and did not evaluate PPEDs. An updated systematic review was completed to focus on PPEDs, novel cancer therapies, and patient-level variables, including those on supportive care alone. Three online databases were used. Included publications were in English, from 2012-2022, with sample sizes of ≥50, and reported predictors of ED presentation or ED diagnoses in oncology. 45 studies were included. Six studies highlighted PPEDs with variable definitions. Common reasons for ED visits included pain (66%) or chemotherapy toxicities (69.1%). PPEDs were most frequent amongst breast cancer patients (13.4%) or patients receiving cytotoxic chemotherapy (20%). Three manuscripts included immunotherapy agents, and only one focused on end-of-life patients. This updated systematic review highlights variability in oncology ED visits during the last decade. There is limited work on the concept of PPEDs, patient-level variables and patients on supportive care alone. Overall, pain and chemotherapy toxicities remain key drivers of ED visits in cancer patients. Further work is needed in this realm.


The Impact of Acupuncture on Postoperative Nausea and Vomiting in Obese Adult Patients Undergoing Laparoscopic Sleeve Gastrectomy: A Randomized Controlled Trial.
Objectives: We wanted to research the effect of acupuncture on postoperative nausea and vomiting (PONV) in morbidly obese adult patients who were scheduled for laparoscopic sleeve gastrectomy. Design: This prospective randomized controlled study included 62 American Society of Anesthesiologists physical status I-III, 18- to 60-year-old morbidly obese patients undergoing laparoscopic sleeve gastrectomy. Patients were assigned using a closed envelope method to both groups equally. Group I consisted of acupuncture and metoclopramide; Group II consisted of metoclopramide. Setting: The study was carried out in Kecioren Educational Research Hospital, University of Health Sciences, Ankara, Turkey. Interventions: Acupuncture was performed by needling PC6, LI4 acupoints bilaterally and Yin Tang acupoint in Group I. Metoclopramide was administered as an antiemetic drug in both groups. Measurements: Demographic parameters, SAMBA PONV risk, first analgesic requirement time and PONV of the patients at the recovery 0-1, 1-6, 6-12, and 12-24 hours after operation were recorded. We used the simplified PONV impact scale to determine the intensity of nausea and its effects on the patient. Results: Nausea was observed in 37.5% of patients in Group I and 63.3% of patients in Group II at the recovery. Nausea intensity was not different between the groups at the postoperative 1-6 hours, but vomiting count was found higher in Group II at the postoperative 12-24 hours. Apfel score of the patients were similar between the groups. PONV impact scale was found higher in Group II. First analgesic requirement time was found shorter and demand for additional analgesic treatment was found significantly higher in Group II. Conclusions: Combining acupuncture with antiemetic treatment reduced nausea intensity and vomiting in the postoperative follow-up period. Also, patient's first analgesic demand time was found longer and the requirement for additional analgesic treatment was found lower in the acupuncture group.


The Krüppel-like factor 2 and Krüppel-like factor 4 genes interact to maintain endothelial integrity in mouse embryonic vasculogenesis.
Krüppel-like Factor 2 (KLF2) plays an important role in vessel maturation during embryonic development. In adult mice, KLF2 regulates expression of the tight junction protein occludin, which may allow KLF2 to maintain vascular integrity. Adult tamoxifen-inducible Krüppel-like Factor 4 (KLF4) knockout mice have thickened arterial intima following vascular injury. The role of KLF4, and the possible overlapping functions of KLF2 and KLF4, in the developing vasculature are not well-studied. Endothelial breaks are observed in a major vessel, the primary head vein (PHV), in KLF2-/-KLF4-/- embryos at E9.5. KLF2-/-KLF4-/- embryos die by E10.5, which is earlier than either single knockout. Gross hemorrhaging of multiple vessels may be the cause of death. E9.5 KLF2-/-KLF4+/- embryos do not exhibit gross hemorrhaging, but cross-sections display disruptions of the endothelial cell layer of the PHV, and these embryos generally also die by E10.5. Electron micrographs confirm that there are gaps in the PHV endothelial layer in E9.5 KLF2-/-KLF4-/- embryos, and show that the endothelial cells are abnormally bulbous compared to KLF2-/- and wild-type (WT). The amount of endothelial Nitric Oxide Synthase (eNOS) mRNA, which encodes an endothelial regulator, is reduced by 10-fold in E9.5 KLF2-/-KLF4-/- compared to KLF2-/- and WT embryos. VEGFR2, an eNOS inducer, and occludin, a tight junction protein, gene expression are also reduced in E9.5 KLF2-/-KLF4-/- compared to KLF2-/- and WT embryos. This study begins to define the roles of KLF2 and KLF4 in the embryonic development of blood vessels. It indicates that the two genes interact to maintain an intact endothelial layer. KLF2 and KLF4 positively regulate the eNOS, VEGFR2 and occludin genes. Down-regulation of these genes in KLF2-/-KLF4-/- embryos may result in the observed loss of vascular integrity.


Plasma immunoreactive N-terminal parathyroid hormone and cyclic AMP and cyclic GMP urinary levels in man after I. M. administration of two different doses of porcine calcitonin.
The effects of acute porcine calcitonin (pCT) administration were studied in 11 healthy volunteers with no metabolic disease. Each subject was given, intramuscularly, 1 MRC unit of pCT in glycine vehicle, 160 units of pCT in gelatine vehicle, and placebo, according to a crossover design. The following parameters were studied: blood calcium, phosphorus and immunoreactive parathyroid hormone (iPTH); urine calcium, phosphorus, cyclic AMP and GMP. Both the pCT preparations produced, at the same time after administration, a hypocalcemic effect (P less than 0.01) which was not dose related, without any modification of urinary calcium excretion, implying that both doses are able to inhibit completely bone destruction. Despite the blood calcium decrease, no significant modifications in plasma iPTH levels were observed. pCT administration did not modify the urinary excretion of cyclic AMP, while it increased the urinary levels of cyclic GMP, particularly at the higher dose employed. Blood phosphorus decrease and urinary phosphate excretion increase were observed only after the administration of 160 MRC units of pCT. These observations suggest that the effects on urinary cyclic GMP and on blood and urine phosphorus are not mediated by PTH but could be the result of a direct action of calcitonin seen only when high doses are employed. In conclusion, one MRC unit of pCT is sufficient to inhibit bone resorption.


[Biomechanical properties of artery in spontaneously hypertensive rats after treating with tetrahydrobiopterin].
To explore the effect of remodeling and biomechanical properties after chronic treating with tetrahydrobiopterin (BH4) in spontaneously hypertensive rats. The spontaneously hypertensive rat(SHR) were given with BH4 chronically. The opening angle in the zero-stress state , wall-to-lumen area ratios (W/L) of thoracic aorta and the relationship between pressure and diameter (P-D) of mesenteric artery were measured by computer image analysis in 4, 16, and 26 week-old respectively. Treating with BH4 chronically from 4 weeks-old in SHR, there was a significant decrease in morphometric parameters of the thoracic aorta and an increase in the zero-stress state of opening angle of elastic artery. The P-D curve of mesenteric artery moved upward. Treating with BH4 prevented the structure and function of artery from abnormal changing, including to attenuate the resistant vascular hypertrophy and recover the vascular elasticity and expansibility.


Safety, efficacy and pharmacokinetics of linezolid for treatment of resistant Gram-positive infections in cancer patients with neutropenia.
Linezolid is a recently approved oxazalidinone with extended activity against Gram-positive bacteria. We evaluated the results of linezolid therapy in neutropenic cancer patients with Gram-positive bacterial infections from a compassionate-use program. This was a prospective, multicenter, open-label, non-comparative, non-randomized compassionate-use treatment program in patients with serious Gram-positive infections. To qualify for enrollment patients were required to have an infection resistant to available antimicrobial agents, or in whom available agents had failed or to which they were intolerant. Patients with absolute neutrophil counts (ANC) <500 cells/mm(3) or <1000 cells/mm(3) and expected to decrease to <500 cells/mm(3), and who received linezolid 600 mg twice daily were included. Plasma samples for population pharmacokinetic analysis were collected. Clinical and microbiological assessments of outcomes were made at the end of therapy and at short-term follow-up. Of the patients in the compassionate-use trial, 103 were neutropenic. The mean [standard deviation (SD)] age was 50.1 (17.5) years, 47% were female, and 47.6% had a baseline ANC </=100 cells/mm(3). The mean (SD) duration of linezolid therapy was 14.6 (11.4) days. The most common site of infection was the bloodstream (90.3%), and the most commonly identified pathogen was vancomycin-resistant Enterococcus faecium (83%). A total of 83 (80.5%) and 52 (50.4%) patients were evaluable for clinical and microbiological outcomes at the end of therapy, respectively. Clinical and microbiological cure rates in the evaluable patients were 79% and 86%, respectively. Linezolid was well-tolerated in this patient population, with an overall adverse event rate of 17.5%; 5% of patients required discontinuation of the drug due to side-effects. The pharmacokinetics of linezolid in patients with neutropenia did not differ from the overall compassionate-use population. Linezolid was safe and effective in treating resistant Gram-positive infections in neutropenic cancer patients. Comparative clinical trials to evaluate further the effectiveness and safety of linezolid in this patient population are warranted.


[Age-related characteristics of antioxidant system in healthy dogs].
The data of the research of age features of oxidation system in dogs are given in the article. As a result, standards on content of lipid peroxidation products in blood in dogs of different age, as well as concentration of antioxidants and activity of enzyme antioxidants have been detected. These data give the assumption that the intensive aging starts from the age of 7 in dogs of large breeds, which indicates to possible correction of age-related changes in this very age.


Cytoprotective activities of kinetin purine isosteres.
Kinetin (N6-furfuryladenine), a plant growth substance of the cytokinin family, has been shown to modulate aging and various age-related conditions in animal models. Here we report the synthesis of kinetin isosteres with the purine ring replaced by other bicyclic heterocycles, and the biological evaluation of their activity in several in vitro models related to neurodegenerative diseases. Our findings indicate that kinetin isosteres protect Friedreich́s ataxia patient-derived fibroblasts against glutathione depletion, protect neuron-like SH-SY5Y cells from glutamate-induced oxidative damage, and correct aberrant splicing of the ELP1 gene in fibroblasts derived from a familial dysautonomia patient. Although the mechanism of action of kinetin derivatives remains unclear, our data suggest that the cytoprotective activity of some purine isosteres is mediated by their ability to reduce oxidative stress. Further, the studies of permeation across artificial membrane and model gut and blood-brain barriers indicate that the compounds are orally available and can reach central nervous system. Overall, our data demonstrate that isosteric replacement of the kinetin purine scaffold is a fruitful strategy for improving known biological activities of kinetin and discovering novel therapeutic opportunities.


Biosimilar infliximab: an expert view.
CT-P13, a biosimilar of infliximab, was the first biosimilar monoclonal antibody to be approved in both the European Union and Korea. As a monoclonal antibody, CT-P13 is a large molecule with a high molecular weight, and as such it differs from other biosimilars currently in the market. The comparability exercise for CT-P13, therefore, requires special consideration, as it was the first demonstration of biosimilarity between a biosimilar monoclonal antibody and its originator. This paper summarizes current regulations on the approval of biosimilars, describes the evidence leading to the approval of CT-P13, and discusses the potential role of this molecule in the Italian scenario on the basis of the view of a group of experts.


Irreducible supracondylar fracture of the humerus complicated by anterior interosseous nerve palsy.
Supracondylar fractures of the humerus are common injuries in childhood and constitute greater than 50% of fractures involving the elbow joint. Neurovascular compromise is not infrequent and has been variously reported as occurring in 5%-17% of displaced fractures. A seven-year-old girl with isolated involvement of the anterior interosseous branch of the median nerve, an uncommon complication, is reported, along with a review of the literature.


Severity of ineffective esophageal motility is associated with utilization of skeletal muscle relaxant medications.
Ineffective esophageal motility (IEM) is the most common finding on high-resolution esophageal manometry (HREM). The underlying mechanisms for IEM remain to be fully elucidated. The aim of this study was to determine if utilization of skeletal muscle relaxants is associated with IEM, and with more severe subtypes of the disorder. Patients with diagnosis of IEM were gender and age matched to patients with normal HREM. Demographic information, symptoms, endoscopic findings, medication usage and medical comorbidities were recorded. Patients with a diagnosis of IEM were divided into subgroups based on mean distal contractile integral (DCI) and percentage of ineffective swallows, and assessed for clinically significant differences among patients with varying severity of underlying IEM. A total of 118 patients were included in each group. There were no significant clinical differences between the group of patients with IEM and the group of patients with normal manometry. Within the group of IEM patients, those with mean DCI < 250 mm Hg/s/cm were more likely to be prescribed skeletal muscle relaxants (27.8% vs 11.0%, P = .044), and those using skeletal muscle relaxants had a larger mean percentage of ineffective swallows (81.1% vs 71.5%, P = .029). There were no significant differences across mean DCI subgroups in usage of any other medication, or in any of the demographic variables or disease comorbidities examined in this study. Use of skeletal muscle relaxants is associated with more severe IEM, which may suggest a causal association between this class of medications and weaker esophageal peristalsis.


Shape information from rotated scans.
In many proposed applications, robots are required to recognize a relatively small number of object types, each well defined by shape. In such cases, relatively simple pattern recognition methods may be adequate. This paper presents a number of exceptionally simple shape discrimination algorithms which exploit the particularly covenient data provided by the combination of a rotating camera and analog edge finder proposed by Miller and Boie.


Emerging influenza viruses and the prospect of a universal influenza virus vaccine.
Influenza viruses cause annual seasonal epidemics and pandemics at irregular intervals. Several cases of human infections with avian and swine influenza viruses have been detected recently, warranting enhanced surveillance and the development of more effective countermeasures to address the pandemic potential of these viruses. The most effective countermeasure against influenza virus infection is the use of prophylactic vaccines. However, vaccines that are currently in use for seasonal influenza viruses have to be re-formulated and re-administered in a cumbersome process every year due to the antigenic drift of the virus. Furthermore, current seasonal vaccines are ineffective against novel pandemic strains. This paper reviews zoonotic influenza viruses with pandemic potential and technological advances towards better vaccines that induce broad and long lasting protection from influenza virus infection. Recent efforts have focused on the development of broadly protective/universal influenza virus vaccines that can provide immunity against drifted seasonal influenza virus strains but also against potential pandemic viruses.


Leiomyosarcoma of the rectum: a series of twelve cases.
Leiomyosarcoma of the rectum is a rare disease without well-documented report on its management and prognosis in Taiwan. To evaluate the effectiveness and prognosis of different treatments for rectal leiomyosarcoma, we reviewed a series of 12 patients with rectal leiomyosarcoma treated at our hospital. This study is a retrospective review of 12 rectal leiomyosarcomas treated at VGH-Taipei from 1976 to 1995, with emphasis on symptoms, therapeutic procedures and prognosis. The majority of tumors occurred in men (n = 10) and the average age at presentation was 54.4 years. Bloody stool and perianal pain were the two most common symptoms. Nine tumors were found in the lower rectum, within 4 cm above the dentate line. Five patients received abdominoperineal resection, four received wide local excision, and three had diversion colostomy. The effect of adjuvant therapy, either chemo- or radiotherapy, was poor. The overall one-year and five-year survival rates were 83% and 46%, respectively. Liver was the principal metastatic site. The local recurrence rate was much higher in patients receiving wide local excision than in those receiving abdominoperineal resection (100% vs. 20%). Abdominoperineal resection is an appropriate choice of treatment for patients with operable rectal leiomyosarcoma due to its lower local recurrence rate. Wide local excision could be considered when the lesion is less than 2 cm in diameter or when patients are not suitable for radical surgery. The effect of adjuvant therapy, either radiotherapy or chemotherapy, is poor for rectal leiomyosarcoma.


Decolorization and detoxification of two textile industry effluents by the laccase/1-hydroxybenzotriazole system.
The aim of this work was to determine the optimal conditions for the decolorization and the detoxification of two effluents from a textile industry-effluent A (the reactive dye bath Bezactive) and effluent B (the direct dye bath Tubantin)-using a laccase mediator system. Response surface methodology (RSM) was applied to optimize textile effluents decolorization. A Box-Behnken design using RSM with the four variables pH, effluent concentration, 1-hydroxybenzotriazole (HBT) concentration, and enzyme (laccase) concentration was used to determine correlations between the effects of these variables on the decolorization of the two effluents. The optimum conditions for pH and concentrations of HBT, effluent and laccase were 5, 1 mM, 50 % and 0.6 U/ml, respectively, for maximum decolorization of effluent A (68 %). For effluent B, optima were 4, 1 mM, 75 %, and 0.6 U/ml, respectively, for maximum decolorization of approximately 88 %. Both effluents were treated at 30 °C for 20 h. A quadratic model was obtained for each decolorization through this design. The experimental and predicted values were in good agreement and both models were highly significant. In addition, the toxicity of the two effluents was determined before and after laccase treatment using Saccharomyces cerevisiae, Bacillus cereus, and germination of tomato seeds.


Conformational dynamics of bacteriophage T7 DNA polymerase and its processivity factor, Escherichia coli thioredoxin.
Gene 5 of bacteriophage T7 encodes a DNA polymerase (gp5) responsible for the replication of the phage DNA. Gp5 polymerizes nucleotides with low processivity, dissociating after the incorporation of 1 to 50 nucleotides. Thioredoxin (trx) of Escherichia coli binds tightly (Kd = 5 nM) to a unique segment in the thumb subdomain of gp5 and increases processivity. We have probed the molecular basis for the increase in processivity. A single-molecule experiment reveals differences in rates of enzymatic activity and processivity between gp5 and gp5/trx. Small angle X-ray scattering studies combined with nuclease footprinting reveal two conformations of gp5, one in the free state and one upon binding to trx. Comparative analysis of the DNA binding clefts of DNA polymerases and DNA binding proteins show that the binding surface contains more hydrophobic residues than other DNA binding proteins. The balanced composition between hydrophobic and charged residues of the binding site allows for efficient sliding of gp5/trx on the DNA. We propose a model for trx-induced conformational changes in gp5 that enhance the processivity by increasing the interaction of gp5 with DNA.


Intravenous lisuride corrects oscillations of motor performance in Parkinson's disease.
Seventeen lisuride infusions were given to 12 patients with Parkinson's disease who showed daily oscillations in motor performance. The mean lisuride dose given in continuous intravenous infusion was 0.59 mg (range, 0.3 to 1.0 mg) during a mean period of 9.0 hours (range, 5 to 12 hours). A significant reduction in the number of hours "off" was obtained in all patients. Additional oral levodopa was necessary to maintain normal mobility throughout the infusions. Severe hypotension occurred in 2 patients which required termination of the infusions. Five patients experienced nausea, sweating, and malaise but this did not necessitate interruption of the infusions. Lisuride appears to be one of the best available dopamine agonists for continuous dopaminergic stimulation.


Patterning of renal cGMP production by the natriuretic peptide receptor type A and blood pressure in spontaneously hypertensive rats.
Although important advances have been made over past decades in studying the mechanisms of hypertension, the nature of cellular signaling patterns involved and their relationship remain unclear. High cGMP production rates in isolated renal glomeruli have been presented as a characteristic of spontaneously hypertensive rat (SHR) even before the development of hypertension, which suggests that this event might be a cause of the increase in blood pressure. Using cross-breeding between SHR and WKY parental strains to obtain F1 and F2 hybrids, we have investigated the patterning of high blood pressure and cGMP production rates. We have found that, in the F2 population, the mean blood pressure and both basal and ANP(1-28)-stimulated cGMP production are similar to the parental SHR. In addition, we have found a positive correlation between blood pressure and high cGMP production rates in the F2 population. The higher cGMP production was not a consequence of hypertension, since in DOCA-salt hypertensive rats cGMP production was similar to that observed in normotensive WKY rats. These observations suggest that high cGMP production is a characteristic linked to hypertension. Finally, reciprocal crosses between the SHR and WKY parental strains showed that in the F1 population blood pressure but not cGMP production are associated with the Y chromosome.


Continuous Venovenous Hemodiafiltration in the Treatment of Maple Syrup Urine Disease.
The study aims to define the efficacy of continuous renal replacement therapy in acute metabolic decompensation treatment of maple syrup urine disease (MSUD). All the neonates, infants and children who have had life threatening conditions due to MSUD and were treated with continuous venovenous hemodiafiltration (CVVHDF) were analyzed retrospectively. Fourteen patients underwent 15 sessions of CVVHDF (age range 15 days to 87 months, mean 40.8 ± 31.4 months). One patient required additional CVVHDF 1 week after cessation of CVVHDF. Twenty seven percent (n = 4) of the patients were intubated and mechanically ventilated. Twelve patients responded to treatment and dramatic neurological improvement was observed within 24 h. Two of the 14 patients required 36 h of CVVHDF for neurological improvement. The mean duration of CVVHDF was 20.2 ± 8.6 (9-36) h. The mean leucine level was 1,648 ± 623.8 (714-2,768) μmol/l before and was 256.5 ± 150.6 (117-646) μmol/l at the end of treatment. No mortality was observed. Continuous hemodiafiltration is an effective and safe method in correcting metabolic disturbances in MSUD.


A novel SATB1 protein isoform with different biophysical properties.
Intra-thymic T cell development is coordinated by the regulatory actions of SATB1 genome organizer. In this report, we show that SATB1 is involved in the regulation of transcription and splicing, both of which displayed deregulation in Satb1 knockout murine thymocytes. More importantly, we characterized a novel SATB1 protein isoform and described its distinct biophysical behavior, implicating potential functional differences compared to the commonly studied isoform. SATB1 utilized its prion-like domains to transition through liquid-like states to aggregated structures. This behavior was dependent on protein concentration as well as phosphorylation and interaction with nuclear RNA. Notably, the long SATB1 isoform was more prone to aggregate following phase separation. Thus, the tight regulation of SATB1 isoforms expression levels alongside with protein post-translational modifications, are imperative for SATB1's mode of action in T cell development. Our data indicate that deregulation of these processes may also be linked to disorders such as cancer.


Selective iodine imaging using K-edge energies in computerized x-ray tomography.
Iodine is commonly used as a contrast material in computerized x-ray tomography. In some cases the determination of the iodine distribution in the image may be prevented by the presence of bone or tissue variations within the tomographic slice. This paper describes a method for quantitative selective imaging of the iodine concentration in the slice. The method employs scans using three heavily filtered x-ray beams, two having mean energies which straddle the iodine K edge (33 keV) and another at a slightly higher energy. The results are independent of tissue and bone over a broad range of projection path lengths. It is shown that, for separation of iodine from one other material, a two-beam K-edge approach requires less integral dose than a two-beam technique at conventional CT energies for slice diameters up to 30 cm. For selective iodine imaging in the presence of more than one other material, the three-spectrum K-edge technique is a necessity. Exposure requirements and beam-hardening corrections are discussed in detail and a computer-simulated CT image generated by the proposed scheme is presented.


The stroke volume/pulse pressure ratio predicts coronary heart disease mortality in a population of elderly men.
The stroke volume to pulse pressure ratio (SV/PP), a measure of total arterial compliance, predicts adverse cardiovascular events in hypertensive subjects. The relations to cardiovascular risk factors and its predictive capacity in the general population are not known. In 1970-73, all 50-year-old men living in Uppsala County, Sweden, were invited to a health survey assessing cardiovascular risk factors. At a reinvestigation 20 years later, 470 subjects underwent an echocardiographic examination, hyperinsulinaemic euglycaemic clamp, oral glucose tolerance test and measurements of blood pressure and lipids. They were thereafter followed for a median of 7.2 years. Serum triglycerides and post-load glucose and insulin levels at age 50 were predictors of SV/PP ratio measured 20 years later (P < 0.05-0.001). At age 70, SV/PP was related to serum non-esterified fatty acids, post-load glucose and insulin levels and insulin sensitivity (P < 0.05-0.001). SV/PP was reduced in subjects with concentric left ventricular hypertrophy (LVH, P < 0.01), and in subjects with a low E-wave to A-wave (E/A) ratio (P < 0.001). The SV/PP ratio predicted mortality from coronary heart disease [hazard ratio 0.54, 95% confidence interval 0.30-0.97 for a one standard deviation (1SD) increase in ln(SV/PP)] independently of left ventricular mass and other major cardiovascular risk factors. Pulse pressure or total peripheral resistance were not significant predictors for future mortality from coronary heart disease. The SV/PP ratio was related to main components of the insulin resistance syndrome, concentric LVH and a low E/A ratio. Furthermore, the SV/PP ratio was an independent predictor of mortality from coronary heart disease in a community-based sample of men aged 70.


Hedonic and Utilitarian Motivations of Home Motion-Sensing Game Play Behavior in China: An Empirical Study.
As an important branch of video games and the integration of emerging motion-sensing technology, home motion-sensing games cannot only bring hedonic entertainment but also promote utilitarian benefits including exercise and social interaction for people to improve their physical and psychological health. As one of the most populous countries in the world, China has the largest number of households in the world but quite a low home game penetration rate due to the 13 year game industry winter for international enterprises. Whether Chinese customers have the intention of using motion-sensing games to improve their health status in the home environment will directly determine the commercial potential of the relevant industry in the Chinese market. In order to understand the motives of users and explore the market possibility and prospects of the game industry, this study adopts empirical research and structural equation modeling to construct a motivation model of Chinese consumers toward motion-sensing gameplay behavior in the household environment. We distributed 515 questionnaires to conduct a survey; 427 valid responses have been received, and 203 data, which meet the inclusion criteria of the required game experience, have been analyzed by SPSS25.0 and AMOS25.0. A structural equation model for the gameplay motivation has been constructed. The result shows that the three functional motivators, exercise (Path efficient = 0.40, p < 0.01), entertainment (Path efficient = 0.27, p < 0.01), and social interaction (Path efficient = 0.36, p < 0.01) of home motion-sensing games have a significantly positive impact on the user's intention to play. Furthermore, the diversity and the time-and-place flexibility variables exert an important positive influence on the users' gameplay behavior through their effects on the three main functional motive variables. To sum up, (1) exercise, (2) entertainment, and (3) social interaction are the main functional motivations of the Chinese consumers' gameplay behaviors; (4) diversity and (5) time-and-place flexibility are the two main attribute motivators. The acceptance of Chinese users for home motion-sensing games remains positive and high. The motion-sensing game industry has broad market prospects in China through its potential in promoting consumer's wellness and health in the home environment.


CIDP Antibodies Target Junction Proteins and Identify Patient Subgroups: An Autoantigenomic Approach.
To discover systemic characteristics in the repertoires of targeted autoantigens in chronic inflammatory demyelinating polyneuropathy (CIDP), we detected the entire autoantigen repertoire of patients and controls and analyzed them systematically. We screened 43 human serum samples, of which 22 were from patients with CIDP, 12 from patients with other neuropathies, and 9 from healthy controls via HuProt Human Proteome microarrays testing about 16,000 distinct human bait proteins. Autoantigen repertoires were analyzed via bioinformatical autoantigenomic approaches: principal component analysis, analysis of the repertoire sizes in disease groups and clinical subgroups, and overrepresentation analyses using Gene Ontology and PantherDB. The autoantigen repertoires enabled the identification of a subgroup of 10/22 patients with CIDP with a younger age at onset and a higher frequency of mixed motor and sensory CIDP. IV immunoglobulin therapy responders targeted 3 times more autoantigens than nonresponders. No CIDP-specific autoantibody is present in all patients; however, anchoring junction components were significantly targeted by 86.4% of patients with CIDP. There are potential novel CIDP-specific autoantigens such as the myelination- or axo-glial structure-related proteins actin-related protein 2/3 complex subunit 1B, band 4.1-like protein 2, cadherin-15, cytohesin-1, epidermal growth factor receptor, ezrin, and radixin. The repertoire of targeted autoantigens of patients with CIDP differs in a systematic degree from those of controls. Systematic autoantigenomic approaches can help to understand the disease and to discover novel bioinformatical tools and novel autoantigen panels to improve diagnosis, treatment, prognosis, or patient stratification.


Trigeminal Neuralgia TRPM8 Mutation: Enhanced Activation, Basal [Ca2+]i and Menthol Response.
To assess the functional effects of a variant, c.89 G > A (p.Arg30Gln), in the transient receptor potential melastatin 8 (TRPM8) cold-sensing, nonselective cation channel, which we have previously identified in a patient with familial trigeminal neuralgia. We carried out Ca2+ imaging and whole-cell patch-clamp recording. The TRPM8 mutation enhances channel activation, increases basal current amplitude and intracellular [Ca2+] in cells carrying the mutant channel, and enhances the response to menthol. We propose that Arg30Gln confers gain-of-function attributes on TRPM8, which contribute to pathogenesis of trigeminal neuralgia in patients carrying this mutation.


Endotoxaemia during left ventricular assist device insertion: relationship between risk factors and outcome.
Endotoxaemia, caused by splanchnic ischaemia during surgery, is believed to trigger systemic inflammation and cause postoperative organ dysfunction. A relationship between the plasma concentration of endotoxin during surgery and known risk factors for postoperative morbidity and mortality (e.g. age, abnormal gastric tonometric variables) and adverse outcome after surgery has not been demonstrated. In a prospective study, the plasma concentration of endotoxin was measured in 12 patients undergoing implantation of a left ventricular assist device. Automated air gastric tonometry was performed in all patients. The relationship between plasma endotoxin concentration, risk factors, and postoperative outcome was explored. Carbon dioxide gap increased from 0.7 (0.3) to 3.6 (1.6) kPa at the end of surgery. Endotoxin was detected in one of 12 patients at baseline and in nine of 12 patients at the end of surgery (P=0.003). A high plasma concentration of endotoxin at the end of surgery was associated with a higher carbon dioxide gap (r=0.59, P<0.05), and a higher postoperative multiple organ dysfunction score (r=0.7, P=0.01). The finding of an association between high intraoperative plasma concentrations of endotoxin, abnormal gastric tonometric variables and adverse outcome supports the view that endotoxaemia is caused by gut hypoperfusion during surgery and is associated with postoperative organ dysfunction.


A simple photonic generation of linearly chirped microwave pulse with large time-bandwidth product and high compression ratio.
Based on the heterodyne beating between the pre-chirped optical pulse and the continuous wave (CW) light in a wideband photodetector (PD), linearly chirped microwave pulse with time duration of 3.2ns and bandwidth of 33GHz, which yields a large time-bandwidth product (TBWP) of 106 and high compression ratio of 160, is generated in our experiment. Dispersion compensation fiber (DCF) with uniform response across broad bandwidth is used for providing the original linear chirp in our method, which shows the promise to generate linearly chirped microwave pulse with bandwidth of up to THz. The flexibility of the center frequency and the stability of the time-frequency performance are demonstrated by generating different types of linearly chirped microwave pulses. The range resolution of our generated microwave pulse is also verified by off-line processing.


Thin blood. Risk of internal bleeding heightened with anticoagulant therapy.
The case detailed here is not uncommon. A day rarely passes at UMC where we don't evaluate and subsequently admit a patient from the Las Vegas valley and surrounding regions that has sustained an intracranial hemorrhage secondary to oral anticoagulants. Because of this, EMS and emergency department personnel should have an increased incidence of suspicion for the possibility of a bleeding complication in patients taking oral anticoagulants. You should always question patients who have atrial fibrillation in regard to oral anticoagulant usage. In the case discussed here, probing questions by paramedics were able to elucidate a history of atrial fibrillation and the use of an oral anticoagulant. This allowed the paramedics to stratify the patient's risk for hemorrhage and need for further medical care. Ultimately, the patient was assessed and transported to a hospital that could care for any possible complications related to the injury.


Clinical experience of 17 cases of imported malaria at a Taiwan university hospital, 1999-2005.
Malaria had been eradicated in Taiwan since 1965, but there are currently 30 to 50 imported cases annually. The management of imported malaria continues to be challenging due to evolving drug resistance of Plasmodium parasites. We retrospectively analyzed the clinical presentations, treatment, and outcomes of all 16 adult patients (17 episodes) with imported malaria diagnosed during 1999-2005. The clinical and laboratory features were obtained from the medical records. Malaria was acquired in sub-Saharan Africa in 6 cases and Southeast Asia in 11 cases. The initial presentations were nonspecific, including fever (17/17 cases), headache (11/17), nausea, vomiting or diarrhea (10/17), cough (3/17), thrombocytopenia (15/17), mild hyperbilirubinemia (13/17), leukopenia (6/17) and anemia (4/17). Careful travel history led to the correct diagnosis in 16 of 17 cases. All 17 cases survived without any recrudescence. Four cases presented with hyperparasitaemia (>5%). Two patients were admitted to an intensive care unit for complicated malaria, and both were cured by artesunate plus mefloquine. Some suboptimal practices, such as non-standard therapeutic regimen and lack of daily parasitemia counting were noted. A differential diagnosis of malaria should be made in all patients who have fever after travel to any endemic area. To further improve the management of imported malaria, timely consultation of an experienced infectious disease specialist is necessary.


Achieving 360° student feedback using SPaCE.
The use of simulated patients (SPs) in undergraduate medical curricula is now an accepted norm. SPs play an important role in the delivery of feedback to medical students. In Dundee, SPs are used in clinical skills teaching sessions from year 1 onwards. Currently SPs provide open feedback to students during communication skills sessions. Rather than giving balanced feedback, SPs can sometimes focus on the negative aspects of a student's performance. This research study developed a closed-feedback tool to be used by SPs to provide constructive feedback to final-year medical students after they have undertaken the Final Year Ward Simulation Exercise (FYWSE). The Simulated Patient Candidate Evaluation (SPaCE) tool was evaluated using a convenience sample of SPs who rated the applicability of the tool by reviewing three previous FYWSE videos. The SPs were able to engage with the SPaCE tool, agreeing that it helped them to identify differences between student's performances. Correlations were shown between the SP's assessment and the marks awarded by the assessment panel. The SPaCE tool is a structured, standardised feedback tool that SPs can complete easily and quickly. The SpaCE tool encourages SPs to provide feedback from specific interactions they have had with students during the FYWSE. In the SP's opinion, good interaction and good interpersonal skills are the determinants of good performance.