Predictive value of red blood cell distribution width for coronary artery lesions in patients with Kawasaki disease.
Recent studies have shown that elevated red blood cell distribution width is associated with poor outcome in cardiovascular diseases. In order to assess the predictive value of red blood cell distribution width, before treatment with intravenous immunoglobulins, for coronary artery lesions in patient with Kawasaki disease, we compared 83 patients with coronary artery lesions and 339 patients without coronary artery lesions before treatment with intravenous immunoglobulin. Clinical, echocardiographic, and biochemical values were evaluated along with red blood cell distribution width. A total of 422 consecutive patients with Kawasaki disease were enrolled into our study. According to receiver operating characteristic curve analysis, the optimal red blood cell distribution width cut-off value for predicting coronary artery lesions was 14.55% (area under the curve was 0.721; p=0.000); eighty-three patients (19.7%) had coronary artery lesions, and 70% of the patients with coronary artery lesions had red blood cell distribution width level >14.55%. Logistic regression analysis revealed that fever duration >14 days (odds ratio was 3.42, 95% confidence interval was 1.27-9.22; p=0.015), intravenous immunoglobulin resistance (odds ratio was 2.33, 95% confidence interval was 1.02-5.29; p=0.04), and red blood cell distribution width >14.55% (odds ratio was 3.49, 95% confidence interval was 2.01-6.05; p=0.000) were independent predictors of coronary artery lesions in patients with Kawasaki disease. In Conclusion, red blood cell distribution width may be helpful for predicting coronary artery lesions in patients with Kawasaki disease.


Cold starting temperature time-related compensation model of inertial sensors based on particle swarm optimization algorithm.
With the miniaturization of inertial instruments, sensors mounted inside are vulnerable to interference. In a complex thermal transmission environment, temperature drift is the main factor restricting the precision of high-performance inertial sensors. To solve this problem, a new method for compensating the time-related cold starting temperature drift of the inertial sensors is introduced in this paper. Based on the perspective that temperature drift can be regarded as the response curve of the sensor system to temperature and temperature gradient, temperature compensation models of first-order, second-order, and higher-order are proposed. Meanwhile, the particle swarm optimization algorithm is used to solve the model parameters. Under various practical circumstances, the method can be used to flexibly compensate the temperature drift and reduce the standard deviation of the output signal by about four times. Compared to other models or algorithms, the simulation and experimental results indicate that the proposed model is superior in adaptability, stability, and reliability.


Sedentary patients with venous or mixed leg ulcers: determinants of physical activity.
This paper is a report of a study to identify the determinants of physical activity (PA) in patients with venous leg ulcers to develop recommendations for behavioural interventions aimed at enhancing physical activity. Physical activity promotes wound healing and prevents the recurrence of wounds in venous patients with leg ulcers. Many patients with leg ulcers, however, have a sedentary lifestyle. A random sample of 25 patients from two clinics were interviewed in 2003 using a combination of prestructured and open-ended questions. All these patients were being treated at an outpatient dermatology clinic and had a leg ulcer with venous or mixed aetiology at the time of the interview or in the month prior to the interview. Only nine of the 25 patients (36%) reported sufficient levels of moderate strenuous physical activity, defined as 30 minutes a day on at least 5 days a week. The results show limited knowledge about the relationship between physical activity and leg ulceration, and low self-efficacy for increasing physical activity. In addition, multi-morbidity, pain and social support were identified as main determinants of physical activity. Suggestions for improving physical activity levels include influencing knowledge, beliefs and self-efficacy. Patient's individual physical limitations, pain, adequate footwear and social support should be taken into account. Programmes offered by specialized dermatology nurses to stimulate physical activity might fulfil patient needs and help enhance physical activity levels.


Increased pedicle screw pullout strength with vertebroplasty augmentation in osteoporotic spines.
The authors conducted a biomechanical study to evaluate pedicle screw pullout strength in osteoporotic cadaveric spines. Nonaugmented hemivertebrae were compared with pressurized polymethylmethacrylate (PMMA)-augmented hemivertebrae. Six formalin-fixed cadaveric thoracolumbar spines at least two standard deviations below the mean bone mineral density (BMD) for age were obtained. Radiographic and BMD studies were correlated to grades I, II, and III osteoporosis according to the Jekei scale. Each of the 21 vertebrae underwent fluoroscopic placement of 6-mm transpedicular screws with each hemivertebra serving as the control for the contralateral PMMA-augmented hemivertebra. Pedicle screws were then evaluated for biomechanical axial pullout resistance. Augmented hemivertebrae axial pullout forces were increased (p = 0.0005). The mean increase in pullout force was 181% for Grade I, 206% for Grade II, and 213% for Grade III osteoporotic spines. Augmented Grade I osteoporotic spines demonstrated axial pullout forces near those levels reported in the literature for nonosteoporotic specimens. Augmented Grade II osteoporotic specimens demonstrated increases to levels found in nonaugmented vertebrae with low-normal BMD. Augmented Grade III osteoporotic specimens had increases to levels equal to those found in nonaugmented Grade I vertebrae. Augmentation of osteoporotic vertebrae in PMMA-assisted vertebroplasty can significantly increase pedicle screw pullout forces to levels exceeding the strength of cortical bone. The maximum attainable force appears to be twice the pullout force of the nonaugmented pedicle screw for each osteoporotic grade.


Visual analysis of data in a multielement design.
Ninety Board Certified Behavior Analysts (BCBAs) and 19 editorial board members evaluated hypothetical data presented in a multielement design. We manipulated the variability, trend, and mean shift of the data and asked the participants to determine if the data demonstrated experimental control. The results showed that variability, trend, and mean shift interacted to affect the participants' ratings of experimental control. The level of agreement between participants was variable, but was generally lower than in previous research.


Phospholipidosis as a function of basicity, lipophilicity, and volume of distribution of compounds.
Drug-induced phospholipidosis (PLD) is an adaptive histologic alteration that is seen with various marketed drugs and often encountered during drug development. Various in silico and in vitro cell-based methods have been developed to predict the PLD-inducing potential of compounds. These methods rely on the inherent physicochemical properties of the molecule and, as such, tend to overpredict compounds as PLD inducers. Recognizing that the distribution of compounds into tissues or tissue accumulation is likely a key factor in PLD induction, in addition to key physicochemical properties, we developed a model to predict PLD in vivo using the measures of basicity (pK(a)), lipophilicity (ClogP), and volume of distribution (V(d)). Using sets of PLD inducers and noninducers, we demonstrate improved concordance with this method. Furthermore, we propose a screening paradigm that includes a combination of various methods to predict the in vivo PLD-inducing potential of compounds, which may be especially useful in lead identification and optimization processes in drug discovery.


Effect of therapy with latamoxef (moxalactam) on carriage of Clostridium difficile.
Twenty-seven patients receiving latamoxef (moxalactam) as a single antimicrobial agent were studied prospectively for Clostridium difficile carriage and development of diarrhoea or colitis. Stools were available prior to therapy from only seven patients, one of whom (14.3%) was an asymptomatic carrier. None of twelve patients studied during therapy were carriers. Seven of 27 patients (25.9%) were colonized with Cl. difficile after completion of latamoxef therapy, and three patients had cytotoxin positive stools. Two patients with cytotoxin grew Cl difficile from stools and one patient was culture negative. Only one patient, who had both culture and cytotoxin positive stools, had profuse diarrhoea. Cl. difficile clinical isolates were only moderately susceptible to latamoxef in vitro. Hamsters given moxalactam developed caecitis. Patients receiving latamoxef, or third generation cephalosporins, may be at increased risk of development of Cl. difficile associated diarrhoea and should be followed closely for this complication, especially after therapy has been discontinued.


High-density surface electromyography: A visualization method of laryngeal muscle activity.
Laryngeal muscle activation is a complex and dynamic process. Current evaluation methods include needle and surface electromyography (sEMG). Limitations of needle electromyography include patient discomfort, interpretive complexity, and limited duration of recording. sEMG demonstrates interpretive challenges given loss of spatial selectivity. Application of high-density sEMG (HD sEMG) arrays were evaluated for potential to compensate for spatial selectivity loss while retaining benefits of noninvasive monitoring. Basic science. Ten adults performed phonatory tasks while a 20-channel array recorded spatiotemporal data of the anterior neck. Data were processed to provide average spectral power of each electrode. Comparison was made between rest, low-, and high-pitch phonation. Two-dimensional (2D) spectral energy maps were created to evaluate use in gross identification of muscle location. Three phonatory tasks yielded spectral power measures across the HD sEMG array. Each electrode within the array demonstrated unique power values across all subjects (P < .001). Comparison of each electrode to itself across phonatory tasks yielded differences in all subjects during rest versus low versus high, rest versus low, and rest versus high and in 9/10 subjects (P < .001) for low versus high phonation. Symmetry of HD sEMG signal was noted. Review of 2D coronal energy maps allowed for gross identification of cricothyroid muscle amidst anterior strap musculature. HD sEMG can be used to identify differences in anterior neck muscle activity between rest, low-, and high-pitch phonation. HD sEMG of the anterior neck holds potential to enhance diagnostic and therapeutic monitoring for pathologies of laryngeal function. NA Laryngoscope, 129:2347-2353, 2019.


Plasmons in the metallic nanoparticle-film system as a tunable impurity problem.
We show that the plasmon resonances of a metallic nanoparticle interacting with the surface plasmons of a metallic film is an electromagnetic analogue of the spinless Anderson-Fano model. This is the same model used to describe the interaction of a localized electronic state with a continuous band of electronic states. The three characteristic regimes of this model are realized here, where the energy of the nanoparticle plasmon resonance lies above, within, or below the energy band of surface plasmon states. These three interaction regimes are controlled by film thickness. The latter regime is experimentally observed and identified.


SpSld3 is required for loading and maintenance of SpCdc45 on chromatin in DNA replication in fission yeast.
Initiation of DNA replication in eukaryotic cells is regulated through the ordered assembly of replication complexes at origins of replication. Association of Cdc45 with the origins is a crucial step in assembly of the replication machinery, hence can be considered a target for the regulation of origin activation. To examine the process required for SpCdc45 loading, we isolated fission yeast SpSld3, a counterpart of budding yeast Sld3 that interacts with Cdc45. SpSld3 associates with the replication origin during G1-S phases and this association depends on Dbf4-dependent (DDK) kinase activity. In the corresponding period, SpSld3 interacts with minichromosome maintenance (MCM) proteins and then with SpCdc45. A temperature-sensitive sld3-10 mutation suppressed by the multicopy of the sna41+ encoding SpCdc45 impairs loading of SpCdc45 onto chromatin. In addition, this mutation leads to dissociation of preloaded Cdc45 from chromatin in the hydroxyurea-arrested S phase, and DNA replication upon removal of hydroxyurea is retarded. Thus, we conclude that SpSld3 is required for stable association of Cdc45 with chromatin both in initiation and elongation of DNA replication. The DDK-dependent origin association suggests that SpSld3 is involved in temporal regulation of origin firing.


Diurnal variation in blood sugar and serum insulin in response to glucose and/or glucagon in healthy subjects.
The role of insulin secretion in the diurnal variation of glucose tolerance has been investigated. In ten healthy subjects, at 08.00 and at 18.00 after 10 hrs of fasting, a combination test of glucose and glucagon was performed. 1 mg glucagon was injected intravenously 40 min after the intravenous infusion of glucose (0.5 g/kg b.w.). Samples for blood sugar (BS) and serum immunoreactive insulin (IRI) were taken before and 2-5 min following the glucose and glucagon loads, and thereafter at 10 min intervals up to 85 min. In the afternoon test, the mean blood sugar values were higher, the differences in the 20-85 min values being statistically significant: the IRI values were statistically lower after glucose, while after glucagon, the increase of serum IRI was apparently similar in both morning and afternoon tests. However, the insulin/glucose ratio (I/G) was significantly lower at 18.00 at 55-85 men. Corresponding results were obtained in six additional healthy subjects when only glucagon (1 mg i.v.) was injected. In this case also, the mean insulin levels were lower in the afternoon after 5 min, while the BS values during the maximal insulin release (2-30 min) were comparable in both the morning and afternoon tests. In the 40-60 min interval, the BS levels were significantly higher in the afternoon. The existence of a diurnal variation in the blood sugar after intravenous glucose load, as well as after glucagon, seems to be correlated to a simultaneous diurnal variation in the insulin response, suggesting decreased pancreatic beta-cell activity in the afternoon.


Leukotrienes B4 and C4 in MS.
Release of leukotriene B4 (LTB4) and leukotriene C4 (LTC4) from neutrophils and platelet-neutrophil suspensions in response to ionophore A23187 was measured in 12 multiple sclerosis (MS) patients and 8 healthy volunteers. LTC4 release from neutrophils, as well as from platelet-neutrophil suspensions, was significantly decreased in MS patients compared with the controls. There was no significant difference in the release of LTB4 between MS patients and controls. The findings suggest that permanent stimulation of platelets and neutrophils e.g., by encephalitogenic peptide leads to continuous LTC4 release with subsequent depletion of intracellular substrates serving as precursors for the formation of 5-lipoxygenase products. Since the target of microvascular actions of LTC4 are postcapillary venules, the release of this sulfidopeptide leukotriene might play a pathogenetic role in the formation of MS lesions.


The Role of transanal (Ta) dissection in the management of difficult primary and recurrent rectal cancer.
The objective of this study was to review the postoperative and short-term oncological outcomes of our first cohort of patients having had a transanal (Ta) approach for primary or recurrent rectal cancer. A retrospective chart review was performed on all cases of Ta dissection occurring between 2013 and 2016. We reviewed data concerning case selection, tumour characteristics, perioperative and postoperative data and final pathology. A total of 24 males were operated for primary (92% (22/24)) or recurrent rectal cancer (8.3% (2/24)). Four patients (16.7% (4/24)) had a history of previous rectal surgery and two had a history of previous Ta total mesorectal excision (TME). A majority of patients were obese, with 58.3% (14/24) having a body mass index >30. The laparoscopic approach was used in the majority of cases (95.8% (23/24)). Most patients had a low anterior resection (95.8% (23/24)). Sixteen patients received a temporary ileostomy (66.7% (16/24)). Three patients suffered perioperative complications (including colonic ischaemia, rectal perforation and arterial bleeding). Five patients (21.7% (5/23)) had an anastomotic leak treated with Ta drainage in two patients. Final pathology revealed negative margins in 95.8% (23/24). TME was considered complete in 87.5% (21/24) overall and in 95% (21/22) when considering only primary cancer cases. According to our cohort of selected difficult cases, Ta dissection approach helped achieve complete mesorectal excision in complex primary rectal cancer but also allowed for rectal resection in patients with previous rectal surgery. This technique also helped perform a primary anastomosis in these difficult cases.


Probabilistic clustering of sequences: inferring new bacterial regulons by comparative genomics.
Genome-wide comparisons between enteric bacteria yield large sets of conserved putative regulatory sites on a gene-by-gene basis that need to be clustered into regulons. Using the assumption that regulatory sites can be represented as samples from weight matrices (WMs), we derive a unique probability distribution for assignments of sites into clusters. Our algorithm, "PROCSE" (probabilistic clustering of sequences), uses Monte Carlo sampling of this distribution to partition and align thousands of short DNA sequences into clusters. The algorithm internally determines the number of clusters from the data and assigns significance to the resulting clusters. We place theoretical limits on the ability of any algorithm to correctly cluster sequences drawn from WMs when these WMs are unknown. Our analysis suggests that the set of all putative sites for a single genome (e.g., Escherichia coli) is largely inadequate for clustering. When sites from different genomes are combined and all the homologous sites from the various species are used as a block, clustering becomes feasible. We predict 50-100 new regulons as well as many new members of existing regulons, potentially doubling the number of known regulatory sites in E. coli.


Sequential transplantation of the liver-kidney-heart from different donors: a case report.
Multi-organ transplantation has emerged as a viable treatment strategy for patients afflicted with multiple organ failure or significant organ dysfunctions. Despite the promising therapeutic outcomes, this approach also amplifies the risk of organ rejection, infection, or neoplastic growth. We present a unique case of a patient who sequentially underwent liver, kidney, and heart transplantation, all sourced from different donors. This case brings forth intriguing possibilities about the interplay between cardiovascular diseases and complications arising post-transplantation, thereby enriching our understanding of comprehensive transplant immunomodulation and cardiovascular disease prevention. A 59-year-old male with chronic alcohol misuse developed liver cirrhosis in 2012 and subsequent kidney failure in 2018 due to alcoholic liver disease, type II diabetes, hyperlipidaemia, and severe hypertension. Subsequently, an incident of extensive transmural myocardial infarction (Killip III) warranted a heart transplant in 2022. Post-transplant, the patient was maintained on a standard immunosuppression regimen with regular post-operative follow-ups. No signs of rejection were noted 1-year post-final transplantation under standard immunosuppression. The presented case exemplifies the potential and feasibility of sequential multi-organ transplantation. The multifaceted interplay between the transplanted organs and the immunosuppressive pharmaceuticals likely exert distinct influences on transplantation immune regulation, possibly diverging from the dynamics observed in single-organ transplantation. A comprehensive exploration of the mechanisms governing immune responses in the context of multi-organ transplantation could yield valuable insights for mitigating graft dysfunction. Furthermore, the rapid progression of atherosclerosis observed after liver and kidney transplantation necessitates further scrutiny to elucidate potential correlations with the post-transplantation state.


Renal failure, paraproteinemia, and lung squamous cell carcinoma.
A 66-year-old man presented with gastrointestinal symptoms and acute renal failure. He had paraproteinemia and tested positive for antinuclear antibodies. There was no evidence for autoimmune disorder or amyloidosis, and bone marrow biopsy was not consistent with multiple myeloma. Three months later he presented with diffuse lymphadenopathy and right lung mass, and lymph node histology revealed metastatic squamous cell carcinoma. This association of paraproteinemia and nonlymphatic neoplasia is unusual and still very rare. A review of the literature is presented.


Massive gastrointestinal bleeding and intestinal perforation in a renal transplant recipient: a case report.
Gastrointestinal (GI) hemorrhage is a problem, the management of which needs the right decision at the right time and close cooperation between physicians and surgeons. We herewith report a renal transplant recipient who developed severe GI bleed and intestinal perforations seven months after renal transplantation. Despite extensive investigations, the exact cause of the problem could not be identified.


Biophysical larval dispersal models of observed bonefish (Albula vulpes) spawning events in Abaco, The Bahamas: An assessment of population connectivity and ocean dynamics.
Biophysical models are a powerful tool for assessing population connectivity of marine organisms that broadcast spawn. Albula vulpes is a species of bonefish that is an economically and culturally important sportfish found throughout the Caribbean and that exhibits genetic connectivity among geographically distant populations. We created ontogenetically relevant biophysical models for bonefish larval dispersal based upon multiple observed spawning events in Abaco, The Bahamas in 2013, 2018, and 2019. Biological parameterizations were informed through active acoustic telemetry, CTD casts, captive larval rearing, and field collections of related albulids and anguillids. Ocean conditions were derived from the Regional Navy Coastal Ocean Model American Seas dataset. Each spawning event was simulated 100 times using the program Ichthyop. Ten-thousand particles were released at observed and putative spawning locations and were allowed to disperse for the full 71-day pelagic larval duration for A. vulpes. Settlement densities in defined settlement zones were assessed along with interactions with oceanographic features. The prevailing Northern dispersal paradigm exhibited strong connectivity with Grand Bahama, the Berry Islands, Andros, and self-recruitment to lower and upper Abaco. Ephemeral gyres and flow direction within Northwest and Northeast Providence Channels were shown to have important roles in larval retention to the Bahamian Archipelago. Larval development environments for larvae settling upon different islands showed few differences and dispersal was closely associated with the thermocline. Settlement patterns informed the suggestion for expansion of conservation parks in Grand Bahama, Abaco, and Andros, and the creation of a parks in Eleuthera and the Berry Islands to protect fisheries. Further observation of spawning events and the creation of biophysical models will help to maximize protection for bonefish spawning locations and nursery habitat, and may help to predict year-class strength for bonefish stocks throughout the Greater Caribbean.


Augmented Reality for Presenting Real-Time Data During Students' Laboratory Work: Comparing a Head-Mounted Display With a Separate Display.
Multimedia learning theories suggest presenting associated pieces of information in spatial and temporal contiguity. New technologies like Augmented Reality allow for realizing these principles in science laboratory courses by presenting virtual real-time information during hands-on experimentation. Spatial integration can be achieved by pinning virtual representations of measurement data to corresponding real components. In the present study, an Augmented Reality-based presentation format was realized via a head-mounted display and contrasted to a separate display, which provided a well-arranged data matrix in spatial distance to the real components and was therefore expected to result in a spatial split-attention effect. Two groups of engineering students (N = 107; Augmented Reality vs. separate display) performed six experiments exploring fundamental laws of electric circuits. Cognitive load and conceptual knowledge acquisition were assessed as main outcome variables. In contrast to our hypotheses and previous findings, the Augmented Reality group did not report lower extraneous load and the separate display group showed higher learning gains. The pre- and posttest assessing conceptual knowledge were monitored by eye tracking. Results indicate that the condition affected the visual relevancy of circuit diagrams to final problem completion. The unexpected reverse effects could be traced back to emphasizing coherence formation processes regarding multiple measurements.


A double-blind clinical study on long-term use of oxyphenbutazone and tolfenamic acid in connection with telecobalt therapy.
Thirty-one patients who suffered from various cancers in the pelvic region were treated in a double-blind clinical long-term study either with placebo, N-(2-methyl-3-chlorophenyl)-anthranilic acid (tolfenamic acid, Clotam) or oxyphenbutazone in order to diminish the local reactions after telecobalt therapy. The results were difficult to judge and no clear differences were seen between the groups. The side-effects were slight and unspecific, except gastrointestinal distresses, which occurred with both tolfenamic acid and oxyphenbutazone, but were more severe with the latter. No significant changes were seen in the blood counts, liver or kidney function tests with tolfenamic acid. In the oxyphenbutazone group S-ALAT, S-AFOS and direct bilirubin were slightly elevated. Blood in feces was more frequent in the drug-treated than in the placebo group. In the light of the present and earlier studies tolfenamic acid appears to cause less side-effects than oxyphenbutazone in prolonged treatment.


Altered saccadic targets when processing facial expressions under different attentional and stimulus conditions.
Depending on a subject's attentional bias, robust changes in emotional perception occur when facial blends (different emotions expressed on upper/lower face) are presented tachistoscopically. If no instructions are given, subjects overwhelmingly identify the lower facial expression when blends are presented to either visual field. If asked to attend to the upper face, subjects overwhelmingly identify the upper facial expression in the left visual field but remain slightly biased to the lower facial expression in the right visual field. The current investigation sought to determine whether differences in initial saccadic targets could help explain the perceptual biases described above. Ten subjects were presented with full and blend facial expressions under different attentional conditions. No saccadic differences were found for left versus right visual field presentations or for full facial versus blend stimuli. When asked to identify the presented emotion, saccades were directed to the lower face. When asked to attend to the upper face, saccades were directed to the upper face. When asked to attend to the upper face and try to identify the emotion, saccades were directed to the upper face but to a lesser degree. Thus, saccadic behavior supports the concept that there are cognitive-attentional pre-attunements when subjects visually process facial expressions. However, these pre-attunements do not fully explain the perceptual superiority of the left visual field for identifying the upper facial expression when facial blends are presented tachistoscopically. Hence other perceptual factors must be in play, such as the phenomenon of virtual scanning.


[A multi-team case-control study on the effects of psychosocial stress to overall health].
To explore the quantitative relationship between the intensity of psychosocial stress and the degree of overall health damages. A multi-group case-control study was designed and implemented. The cases included two groups of out-patients (177) and in-patients (214) in a hospital in Jianyang city, and controls (587) were from the follow-up cohort in the same city. Three groups were studied on the following contents: general demographic characteristics, psychosocial factors and the degree of health damages including mental, physical, and social status. Major statistical analyses were as follows: ranks test, ANOVA, cluster analysis, multinomial logistic regression and ordered-logit regression. Ordered-logit regression model showed that the odds ratio of negative life-events on degree of health damages was 1.335 (P < 0.01). This result showed that there was a positive dose-effect relationship between the negative life-events score and overall health damages. The utility of social support to overall health had protective effect (OR = 0.513). Negative life-events were the major risk factors to overall health, and there was a dose-effect relationship between negative events and health damages. Function of social support played a protective factor for health.


A comprehensive pelvic dissection course improves obstetrics and gynecology resident proficiency in surgical anatomy.
This study was undertaken to evaluate the impact of a pelvic dissection course on resident proficiency in surgical anatomy. Over a 1-year period, residents attended a course consisting of pretesting and posttesting, lectures, and pelvic dissection. Tests results were analyzed using paired Student t test, analysis of variance, and Kruskal-Wallis statistics. Of 42 residents, 24 completed all testing (study cohort). On written and practical examinations, resident scores improved a median of 42% and 29% (both P<.0001). Postgraduate year (PGY) 2 demonstrated the greatest improvement on the practical and PGY-3s demonstrated the greatest improvement on the written. Baseline written and practical results discriminated PGY level (construct validity): PGY-2=PGY-3<PGY-4 on written pretest, PGY-2<PGY-3=PGY-4 on practical pretest. No difference between resident cohorts was seen in either posttest. Resident surgical anatomy proficiency is measurably improved by a comprehensive course.


Localized malignant pleural mesothelioma showing a thoracic mass and metastasizing to the stomach.
Malignant mesothelioma typically shows either diffuse tumors or multiple pleura-based nodules. Localized malignant mesothelioma is rare. In this case report, a 70-year-old man with left chest wall tumor underwent tumor resection, and the lesion was pathologically diagnosed as biphasic malignant mesothelioma. Tumor recurrence was detected in the stomach due to vomiting of blood, and also spread to the mediastinal lymph node, and bone 3 months postoperatively. Total gastrectomy was performed and the histopathological diagnosis of metastasis of mesothelioma was made. In the previously reported cases, all of the localized malignant mesothelioma arose in the pleural space and there was no metastasis of localized malignant mesothelioma to the stomach. In the present case, gross and histological examinations were performed for both the primary lesion and gastric metastatic tumor. Though it was very difficult to distinguish mesothelioma from sarcoma and other chest wall tumors, immunochemical staining was able to facilitate making the diagnosis. This case suggests that localized malignant mesothelioma is capable of showing multiple forms and a variety of clinical courses. Localized malignant mesothelioma can arise primarily from the chest wall.


circRNA expression patterns and circRNA-miRNA-mRNA networks during CV-A16 infection of SH-SY5Y cells.
Coxsackievirus A16 (CV-A16) has caused worldwide epidemics of hand, foot, and mouth disease (HFMD) in infants and preschool children. Circular RNAs (circRNAs), a class of noncoding RNA molecules, participate in the progression of viral infectious diseases. Although the function of circRNAs has been a heavily researched topic, their role in CV-A16 infection is still unclear. In this study, the viral effects of CV-A16 on the cellular circRNA transcriptome were investigated using next-generation sequencing technology. The results showed that a total of 8726, 8611, and 6826 circRNAs were identified at 0, 12, and 24 h postinfection, respectively. Moreover, it was found that 1769 and 1192 circRNAs were differentially expressed in at 12 and 24 h postinfection, respectively. The common differentially expressed circRNAs were used for functional annotation analysis, and it was found that the parent genes of differentially expressed circRNAs might be associated with the viral infection process, especially the "Immune system process" in GO analysis and the "Inflammation mediated by chemokine and cytokine signaling pathway" in KEGG analysis. Subsequently, circRNA-miRNA-mRNA regulatory networks were constructed, and the hsa_circ_0004447/hsa-miR-942-5p/MMP2, hsa_circ_0078617/hsa-miR-6780b-5p/MMP2 and hsa_circ_0078617/hsa-miR-5196-5p/MMP2 regulatory axes were identified by enrichment analysis as important networks during the progression of CV-A16 infection. Finally, six dysregulated circRNAs were selected for validation and were verified to be consistent with the sequencing results. Considering all of these results, to the best of our knowledge, this study is the first to present a comprehensive overview of circRNAs induced by CV-A16 infection, and this research demonstrated that a network of enriched circRNAs and circRNA-associated competitive endogenous RNAs (ceRNAs) is involved in the regulation of CV-A16 infection, thereby helping to elucidate the mechanisms underlying CV-A16-host interactions.


Slaughter of Pregnant Cattle in Denmark: Prevalence, Gestational Age, and Reasons.
The slaughter of pregnant cattle gives rise to ethical controversy. We estimated the prevalence of pregnant cattle, elucidated the reasons for their slaughter, and in light of our findings, discussed the ethics of sending pregnant cattle for slaughter. Among 825 female cattle >353 days of age admitted to a Danish abattoir, 187 (23%) were found to be pregnant. There was no apparent difference in the proportion of pregnant animals between dairy and non-dairy cattle. "Health"-related slaughter was most frequent in dairy herds (70%), whereas "production"-related slaughter was most frequent in non-dairy herds (63%). While many farmers considered it unethical to slaughter pregnant cows without a good reason for doing so, many dairy farmers identified animal welfare as an important parameter in the decision, which was typically when the general condition of the cow or heifer would make it difficult for her to pass through calving and subsequent lactation. The many pregnant animals sent for slaughter were often the result of deliberate choices. Non-dairy farmers often kept a bull with their female cattle, and in many instances, this resulted in the mating of cattle intended for slaughter. Although considered ethically problematic by many dairy farmers, the slaughter of pregnant dairy cattle was often considered better for the cow compared to a stressful lactation period.


Photochemical Oxidation of Thioketones by Singlet Molecular Oxygen Revisited: Insights into Photoproducts, Kinetics, and Reaction Mechanism.
Photosensitized oxidation of trimethyl[2.2.1]bicycloheptane thioketones by (1)O2 can yield more photoproducts than exclusively ketones and sulfines. Moreover, the ketone/sulfine ratio can be reversed when protic conditions and high thioketone concentrations are used, conversely to earlier results reporting ketones as the main photoproducts. A new mechanistic proposal for sulfine formation is suggested following intermolecular oxygen transfer from a peroxythiocarbonyl intermediate to a second thioketone molecule. Reaction quantum yields (10(-5)-10(-2)) depend on the reaction conditions and time. Sulfine production reaches a maximum at short irradiation times, whereas decomposition to the corresponding ketone is observed at long reaction times. When the thioketone substrate has a hydrogen atom at the α position a peroxyvinylsulfenic acid intermediate can be formed by proton transfer. Reaction of this intermediate with another thioketone molecule can yield more sulfine and its tautomeric vinylsulfenic acid, which dimerizes in situ to the thiosulfinate. The hydroperoxyl group of the peroxyvinylsulfenic acid can also rearrange to the α position, and by reaction with the starting thioketone, α-hydroxy thioketone and additional sulfine can be formed, while dehydration yields the α-oxo thioketone. In situ [2 + 2] and [4 + 2] self-cycloaddition of the α-oxo thioketone yields significant amounts of the corresponding adducts at prolonged irradiation times.


Modulation of soleus H-reflexes during gait in children with cerebral palsy.
In healthy adults, soleus H-reflexes are rhythmically modulated and generally depressed during gait compared with rest. From ages 6 to 13 yr, there is a progressive increase in the tonic inhibition of H-reflexes during walking, especially during the stance phase of the step cycle. In adults, rhythmic modulation and tonic depression are severely disturbed after bilateral spinal lesions but remain partly preserved after unilateral cerebral lesions. Children with diplegic cerebral palsy (CP) suffer from a bilateral supraspinal lesion of the corticospinal tract that occurs before the maturation of the CNS is complete. If supraspinal structures are involved in the tonic, but not rhythmic, age-dependent reflex depression, it could be hypothesized that the tonic reflex depression with age is disturbed in CP, whereas the rhythmic part of the modulation remains unaffected. To test this hypothesis, soleus H-reflexes were assessed during gait in 16 CP children aged 5-11 and 15-16 and compared with 25 age-matched healthy children walking at similar velocities. Although the rhythmic part of the modulation pattern was present in CP, there was no significant tonic reflex depression with age, thus reflecting a lack of maturation of the corticospinal tract. It is argued the rhythmic part of the modulation may be generated on a spinal or brain stem level and is therefore not affected by the bilateral supraspinal lesion, whereas the tonic depression that occurs with maturation of the CNS is under supraspinal control. In conclusion, the supraspinal structures affected in CP are therefore likely involved in this age-dependent tonic depression.


Magnetophoretic continuous purification of single-walled carbon nanotubes from catalytic impurities in a microfluidic device.
A magnetophoretic continuous purification method is presented of single-walled carbon nanotubes (SWCNTs) from the superparamagnetic iron-catalyst impurities in a microfluidic device without any influence on inherent SWCNT properties. By employing microfluidics and a magnetic-field-induced saw-tooth nickel microstructure, a highly enhanced magnetic force in adjoining microchannels is exploited. The iron impurities of SWCNTs are attracted towards areas of higher magnetic-flux density in the microchannels where magnetic field was asymmetrically generated perpendicularly to the streamline. We obtained highly purified SWCNTs at a rate of 0.36 mg h(-1) and that are estimated to be about 99% purity.


FlyNap (triethylamine) increases the heart rate of mosquitoes and eliminates the cardioacceleratory effect of the neuropeptide CCAP.
FlyNap (triethylamine) is commonly used to anesthetize Drosophila melanogaster fruit flies. The purpose of this study was to determine whether triethylamine is a suitable anesthetic agent for research into circulatory physiology and immune competence in the mosquito, Anopheles gambiae (Diptera: Culicidae). Recovery experiments showed that mosquitoes awaken from traditional cold anesthesia in less than 7 minutes, but that recovery from FlyNap anesthesia does not begin for several hours. Relative to cold anesthesia, moderate exposures to FlyNap induce an increase in the heart rate, a decrease in the percentage of the time the heart contracts in the anterograde direction, and a decrease in the frequency of heartbeat directional reversals. Experiments employing various combinations of cold and FlyNap anesthesia then showed that cold exposure does not affect basal heart physiology, and that the differences seen between the cold and the FlyNap groups are due to a FlyNap-induced alteration of heart physiology. Furthermore, exposure to FlyNap eliminated the cardioacceleratory effect of crustacean cardioactive peptide (CCAP), and reduced a mosquito's ability to survive a bacterial infection. Together, these data show that FlyNap is not a suitable substitute to cold anesthesia in experiments assessing mosquito heart function or immune competence. Moreover, these data also illustrate the intricate biology of the insect heart. Specifically, they confirm that the neurohormone CCAP modulates heart rhythms and that it serves as an anterograde pacemaker.


Release of the soluble interleukin-6 receptor from human T-cells.
The soluble Interleukin-6 receptor (sIL-6R) is capable of conferring the Interleukin-6 (IL-6) signal onto cells lacking the gp80 ligand binding protein. Here we investigate the release of sIL-6R from T-cells. After 2 h stimulation with PMA, a release of sIL-6R from peripheral human T-cells was observed which was insensitive to the protein synthesis inhibitor cycloheximide. This release was accompanied by a decrease of membrane-bound (mb) IL-6R. After 24 h, however, the observed sIL6-R release did prove to be sensitive to cycloheximide. These results suggest that both shedding and denovo-synthesis may be responsible for the PMA-induced sIL-6R release. In contrast to PMA, neither anti-CD3, a positive, nor IL-10, a negative regulator of IL-6 release from T-cells affected the production of the sIL-6R. The differential regulation of sIL-6R and IL-6 production by T-cells might be relevant for the immunomodulatory potential of the sIL-6R with respect to the interaction of T- and non-T-cells.


The Evolving HIV-1 Epidemic in Warao Amerindians Is Dominated by an Extremely High Frequency of CXCR4-Utilizing Strains.
We previously reported a high prevalence of HIV-1 infection in Warao Amerindians from Venezuela due to the rapid spread of a single B subtype strain. In this study we evaluated the coreceptor use of the HIV-1 strains infecting this Amerindian community. Sequences of the HIV-1 V3 loop from 56 plasma samples were genotyped for coreceptor use. An extremely high frequency of CXCR4 strains was found among HIV-1-infecting Waraos (47/49, 96%), compared to HIV-1 strains infecting the non-Amerindian Venezuelan population (35/79, 44%, p < 0.00001). Evolutionary analysis showed that a significant number of infections occurred between 1 and 12 months before collection and that a great proportion (50-70%) of HIV-1 transmissions occurred within the very early phase of infection (≤12 months). This is consistent with an initial infection dominated by an X4 strain or a very rapid selection of X4 variants after infection. This Amerindian population also exhibits the highest prevalence of tuberculosis in Venezuela, being synergistically bad prognostic factors for the evolution of morbidity and mortality in this vulnerable population.


Lymphatic fistulas: obliteration by low-dose radiotherapy.
Lymphatic drainage from the surgical wound is an uncommon but challenging complication of surgical intervention. Protracted lymphorrhea contributes to morbidity, favors infections and results in a prolonged hospital stay. Treatment options include surgical ligation and, more conservatively, leg elevation, continuous local pressure, subatmospheric pressure dressings, and low-dose radiotherapy. This study examines the efficacy of low-dose radiotherapy. 17 patients (19 fistulas) with lymphorrhea following vena saphena harvesting (n = 7), femoropopliteal bypass (n = 3), varicose vein surgery (n = 2), hip arthroplasty (n = 3; five fistulas), shunt surgery (n = 1), and piercing (n = 1) were referred for external radiotherapy. Depending on the depth of the fistula, orthovoltage (n = 12), electrons (4-11 MeV; n = 2) or photons (8 MV; n = 3) were used. Fractions between 0.3 Gy and 2 Gy were applied; the individual total dose depended on the success of the radiotherapy, i. e., the obliteration of the lymph fistula, and varied from 1 to 12 Gy. In 13 out of 17 patients complete obliteration of the fistula was achieved. Interestingly, this was achieved in nine of the ten patients irradiated with total doses of </=3 Gy and with fraction sizes ranging from 0.3 to 0.5 Gy. In one patient with hip arthroplasty, only two out of three fistulas disappeared after 12 Gy and in a further three cases no distinct benefit was observed after 2.4 Gy, 8 Gy, and 10.5 Gy, respectively. No treatment-related side effects occurred. Radiotherapy represents an efficacious and economical treatment option in cases of persistent lymphorrhea and is able to reduce the risk of secondary infection, to decrease the duration of hospitalization, and to reduce overall costs for the individual patient. Daily scoring of treatment efficacy is recommended, because radiotherapy can be terminated as soon as lymphorrhea has stopped. Very low total doses with 0.3-0.5 Gy fraction size are recommended up to a maximum of 10-12 Gy in nonresponders.


M-score: a knowledge-based potential scoring function accounting for protein atom mobility.
A knowledge-based potential scoring function, named M-Score, has been developed based upon 2331 high-resolution crystal structures of protein-ligand complexes. M-Score considers the mobility of protein atoms, describing the location of each protein atom by a Gaussian distribution instead of a fixed position based upon the isotropic B-factors. This leads to an increase in the number of atom-pairs in the construction of knowledge-based potentials and a smoothing effect on the pairwise distribution functions. M-Score was validated using 896 complexes which were not included in the 2331 data set and whose experimentally determined binding affinities were available. The overall linear correlation coefficient (r) between the calculated scores and experimentally determined binding affinities (pKi or pKd) for these 896 complexes is -0.49. Evaluation of M-Score against 17 protein families showed that we obtained good to excellent correlations for six protein families, modest correlations for four protein families, and poor correlations for the remaining seven protein families.


Prolonged norovirus shedding in infants <or=6 months of age with gastroenteritis.
Noroviruses (NV) are one of the leading causes of gastroenteritis in young children; however, the duration of NV shedding in young children is not well known. Fecal specimens were collected from children with acute gastroenteritis at a pediatric clinic during the period from November to December 2002 and tested for NV by reverse transcription-polymerase chain reaction. Of 71 children infected with NV, 60 (84.5%) were less than 3 years old. Among children aged <2 years and those aged 2 to 5 years, the duration of illness was longer (7 days versus 3.5 days, P = 0.0069), the maximum number of stools in a 24-hour period was greater (7 versus 3, P = 0.0078) and a 20-point severity score was higher (11 versus 8, P = 0.0031) in patients aged <2 years than in patients aged 2 to 5 years. Among the 23 children whose follow-up specimens were obtained, the median duration of NV shedding was 16 days (range, 5-47 days). Virus shedding for more than 2 weeks after onset was observed in 75% (6 of 8), 71.4% (5 of 7) and 25% (2 of 8) of children aged <1 year, 1 year and 2 to 3 years, respectively. Three infants aged <or=6 months continued to excrete NV for an extremely long period (more than 42, 44 and 47 days from onset) after recovery. Long-term virus shedding after the disappearance of clinical symptoms was observed. Caution should be exercised when handling the excrement of infants and young children infected with NV.


Enhanced extraction of phenol from model oils using ionic liquids elucidated with neutron diffraction.
Aromatic cation ionic liquids (ILs) based on alkylpyridiniums are shown to be good phenol extractants from model oils (hexane/toluene). ILs with hard basic anions are found to have best extraction efficiency consistent with tetraalkylammonium salts ([NR4]X). Key extraction interactions were analysed using small angle neutron diffraction. Trifluoromethanesulphonate ([OTf]- or triflate) anions provide the synergistic effects of reduced cation-phenol centre of mass (COM) distances and increased hydrogen bonding that are linked to the improved extraction efficiency. Increases in cation electron density (methylpyridinium ([Me-Py]+) vs. methylpicolinium ([Me-3-Pic]+)) also reduce cation-phenol COM interaction lengths consistent with small increases in extraction efficiency for the same ionic liquids.


Prolonged length of hospital stay in Denmark after nephrectomy.
Implementation of the principles of a fast-track surgical programme resulted in a decrease in the length of hospital stay after open nephrectomies. The aim of this study was to describe the regional distribution of nephrectomies, postoperative hospital stay and mortality. This study was based on data extracted from the Danish National Patient Registry for the 2000-2009-period. A total of 6,790 nephrectomies were performed. The mean postoperative stay and mortality decreased from 10.1 days and 2.6% during the 2000-2004-period to 8.3 days (p > 0.05) and 1.7% (p < 0.05) during the 2005-2009-period. A significant decrease in length of postoperative stay (6.4 versus 9.0 days; p < 0.05) and mortality (0.9% versus 2.1%; p < 0.05) was found between laparoscopic and open nephrectomies, respectively, during the 2005-2009-period. Nephrectomies performed by laparoscopic technique rose from 7.6% to 30.8% (p < 0.05) and laparoscopic nephroureterectomies from 1.7% to 10.3% (p < 0.05) from the 2000-2004-period to the 2005-2009-period. We recommend the implementation of fast-track surgery programmes to further decrease postoperative stay and mortality. A further increase in the use of laparoscopy is warranted.


Infectious problems in elective non-colorectal abdominal surgery. The Norwegian Gastro-Intestinal Group (NORGAS).
The incidence of post-operative infectious complications after high-risk biliary and gastroduodenal and all cases of small bowel surgery was investigated in 965 patients included in a prospective multi-centre study. Selected types of operation where antibiotic prophylaxis was considered beneficial were defined and patients in these categories were to receive a standardized prophylactic regimen of 400 mg doxycycline plus 1600 mg tinidazole intravenously 1-hour pre-operatively or at induction of anaesthesia. Of the 965 patients, 408 did not receive prophylaxis, 547 received the standard regimen and 10 were given a different prophylaxis. The overall compliance rate with the protocol was 89%. Analysis of the results of clinical evaluation of the patients 3, 7 and 15 days after surgery showed that only 21 (2.1%) of the 965 patients had developed surgical infectious complications. Two (0.2%) patients died of septic complications. No serious side-effects of the prophylactic regimen were recorded.


Rituximab Dosing in Glomerular Diseases: A Scoping Review.
Rituximab is increasingly prescribed for glomerular diseases. However, the recently published Kidney Disease Improving Global Outcomes (KDIGO) 2021 Clinical Practice Guideline for the Management of Glomerular Diseases lacks details on recommended dosing regimens for most individual glomerular diseases. We performed this scoping review summarizing the evidence for rituximab dosing in glomerular disease. PubMed database. The PubMed search methodology was developed with a medical librarian and performed by the first, with review by a second, author. Randomized controlled trials (RCTs) and prospective cohort studies (PCSs) examining rituximab efficacy and/or safety in antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), membranous nephropathy (MN), lupus nephritis (LN), or podocytopathies (minimal change disease or focal segmental glomerulosclerosis [FSGS]) were included. Fifty-three studies (14 RCTs and 39 PCSs) were included. We identified 16 different rituximab dosing regimens studied as induction therapy for one or more of the 5 glomerular diseases of interest. The most frequently studied rituximab induction regimens were 1000 mg as 2 doses 2 weeks apart (17 studies, 32%) and 4 doses of 375 mg/m2/week (18 studies, 33.9%). Twenty-six studies (49%) examined rituximab as monotherapy or in conjunction with corticosteroids alone, while the remaining studies examined rituximab as part of combination immunosuppression. Adapting treatment to achieve B-cell depletion, with frequent evaluation of disease-specific biomarkers, might prove the optimal approach to achieving and maintaining remission. Rituximab might also enable steroid minimization or avoidance. Restriction of the search to a single database and to studies published in the English language, and with an accompanying abstract, could have led to selection bias. While the search was limited to prospective observational studies and RCTs, no formal assessment of study quality was performed.


Long-term antibiotic treatment of chronic bacterial prostatitis. Effect on bacterial flora.
The bacterial flora in patients referred with chronic bacterial prostatitis were studied. Only 13% had Gram-negative bacteria in significant numbers but 43% had Gram-positives using the same criteria. Half of the patients were symptom-free by the end of a 12-week course of antibiotics and remained so after 6 months; in one-third the symptoms were unchanged 6 months after completing treatment. The relief of symptoms correlated with the disappearance of white blood cells in the expressed prostatic secretion (EPS) and with a lowered pH in the EPS. Thus only 1 of the 14 patients without symptoms at 6 months had a significant growth of bacteria at the prostatic level, whereas 7 of 10 patients with unchanged symptoms had a significant bacterial colonisation. Although the initially infecting organism was eliminated in about half of the patients, new Gram-positive bacteria were isolated after treatment in 13 of 29 patients; 12 of these resolved spontaneously within 6 months. Five patients with Gram-positive bacteria were colonised with new Gram-negatives at the end of treatment. Two healed spontaneously but 3 remained colonised with Gram-negatives at the end of the follow-up period. These findings make it likely that many patients infected with Gram-positive bacteria benefit from antibiotic treatment. However, disturbances in the bacterial flora by antibiotic treatment may facilitate invasion by new types of bacteria.


Chemical segregation in metallic glass nanowires.
Nanowires made of metallic glass have been actively pursued recently due to the superb and unique properties over those of the crystalline materials. The amorphous nanowires are synthesized either at high temperature or via mechanical disruption using focused ion beam. These processes have potential to cause significant changes in structure and chemical concentration, as well as formation of defect or imperfection, but little is known to date about the possibilities and mechanisms. Here, we report chemical segregation to surfaces and its mechanisms in metallic glass nanowires made of binary Cu and Zr elements from molecular dynamics simulation. Strong concentration deviation are found in the nanowires under the conditions similar to these in experiment via focused ion beam processing, hot imprinting, and casting by rapid cooling from liquid state. Our analysis indicates that non-uniform internal stress distribution is a major cause for the chemical segregation, especially at low temperatures. Extension is discussed for this observation to multicomponent metallic glass nanowires as well as the potential applications and side effects of the composition modulation. The finding also points to the possibility of the mechanical-chemical process that may occur in different settings such as fracture, cavitation, and foams where strong internal stress is present in small length scales.


2-Amino-5-oxo-4-phenyl-5,6,7,8-tetra-hydro-4H-chromene-3-carbonitrile.
In the title mol-ecule, C(16)H(14)N(2)O(2), the fused cyclo-hexene and pyran rings adopt an envelope and a flattened boat conformation, respectively. In the crystal, N-H⋯N and N-H⋯O hydrogen bonds link the mol-ecules into corrugated sheets parallel to the bc plane.


[Arthroscopic treatment for calcaneal spur syndrome].
PURPOSE OF THE STUDY Arthroscopic treatment of calcaneal spur syndrome is a tissue-sparing and effective approach when conservative therapy has failed. This method, its results and our experience with the treatment of this syndrome are presented here. MATERIAL Between January 2003 and November 2007, 26 patients underwent an arthroscopic procedure for calcaneal spur syndrome; of these, 20 were women with an average age of 49 years, and six were men with an average age of 45 years. Four, three women and one man, were lost to follow-up, therefore 22 patients with 24 heels were eventually evaluated. All had conservative therapy for 3 to 6 monts. METHODS The arthroscopic method used was developed by the arthroscopic group of the Orthopaedic Service of Hospital Hermanos Ameijeiras in Havana, Cuba. The surgical technique insolves treatment of the spur and plantar fasciitis commonly found in calcaneal spur syndrome, but it also addresses adjacent calcaneal periostitis. RESULTS The results were evaluated on the scale that is part of the foot function index developed by Budiman-Mak for measuring rheumatoid arthritis pain. The patients were asked mine questions on pain intensity during various activities before and after surgery. Pain was evaluated on a scale with grades from 0 to 9. The average value was 5.9 before surgery and 1.4 after surgery. A 0-1 pain range was reported by 25 %, 1-2 by 26 % and 2-4 by 22 % of the patients. All patients reported improvement. DISCUSSION The orthopaedic group in Havana led by Carlos achieved 85 % excellent outcomes (pain range, 0-2) at one-year followup; this was 79 % in our study, in which no problems with foot arches or wound infection were recorded. CONCLUSIONS The heel spur syndrome is a result of an inflamed ligament (plantar fascia) due to repeated microtrauma. It is not a traction osteophyte,but a reaction of the tissue where it attaches to the calcaneus. Adjacent calcaneal periostitis is usually present as well. Therefore, this method treting all three causes of the syndrome appears to be more effective than mere fasciotomy.


[Colorectal cancer: classification and aspects of the proliferation kinetics].
The exact tumor classification by the pathologist is the basis of adequate therapy of colorectal carcinomas. The classification includes the determination of the histological type of the carcinoma and the grading according to the criteria of the WHO and the UICC, as well as the staging according to the TNM system of the UICC and the Dukes classification. Most colorectal carcinomas are adenocarcinomas of tubular, tubulo-papillary and papillary subtypes. Mucinous adenocarcinomas are characterized by a pronounced extracellular mucus production. Signet ring cell carcinomas with intracellular mucus production are very rare and predominantly localized in the right-sided colon. Adeno-squamous carcinomas and squamous cell carcinomas are extremely rare in the large bowel. They are only mentioned for completeness. The histological grading proposed by the WHO distinguishes carcinomas of well (G1), moderately well (G2) and poor (G3) differentiation. Well and moderately well differentiated tumors can be regarded as carcinomas with low grade of malignancy, whereas poorly differentiated ones are carcinomas with high grade of malignancy. The new grading of the UICC distinguishes in addition to the well, moderately well and poorly differentiated carcinomas the undifferentiated tumors (G4). G1 and G2 correspond to low grade, G3 and G4 to high grade of malignancy. According to the 1987 nomenclature of the UICC-TNM system pT1 denotes tumor spread to the mucosa, or mucosa and submucosa, pT2 to the muscularis propria, pT3 into the subserosa or into nonperitonealized pericolic or perirectal tissue and pT4 a perforation of the visceral peritoneum or a spread into other organs.(ABSTRACT TRUNCATED AT 250 WORDS)


Dynamic Factors for Transmitter Release at Small Presynaptic Boutons Revealed by Direct Patch-Clamp Recordings.
Small size of an axon and presynaptic structures have hindered direct functional analysis of axonal signaling and transmitter release at presynaptic boutons in the central nervous system. However, recent technical advances in subcellular patch-clamp recordings and in fluorescent imagings are shedding light on the dynamic nature of axonal and presynaptic mechanisms. Here I summarize the functional design of an axon and presynaptic boutons, such as diversity and activity-dependent changes of action potential (AP) waveforms, Ca2+ influx, and kinetics of transmitter release, revealed by the technical tour de force of direct patch-clamp recordings and the leading-edge fluorescent imagings. I highlight the critical factors for dynamic modulation of transmitter release and presynaptic short-term plasticity.


Requirement of CD4-positive T cells for cellular recruitment to the lungs of mice in response to a particulate intratracheal antigen.
To determine whether CD4+ T cells participate in the recruitment of other lymphocyte subsets to the lungs, we examined pulmonary immune responses in C57BL/6 mice treated in vivo with the MAb GK1.5, either intact (which depletes CD4+ cells) or as F(ab')2 fragments (which block CD4 molecules). After intratracheal challenge with sheep erythrocytes, antigen-primed mice treated with intact GK1.5 had marked decreases in lymphocytes and macrophages in bronchoalveolar lavage fluid and minimal parenchymal inflammation, compared to primed mice treated with an isotype-matched irrelevant antibody or with no antibody. At 7 d after challenge, flow cytometric analysis showed that numbers of Thy 1.2+ and B220+ cells, but not of CD8+ cells, were markedly decreased in lavage fluid of CD4-depleted mice. Similar suppression of the pulmonary immune response to intratracheal challenge was found in primed mice injected repeatedly with F(ab')2 fragments of GK1.5, which did not deplete CD4+ T cells, and in athymic mice. These findings indicate that, in response to a single intratracheal antigen challenge, recruitment to the lungs of leukocytes other than CD8+ T cells depends largely on CD4+ T cells, possibly because of signals requiring T cell activation via interactions with antigen-presenting cells.


The effect of oral folic acid on glutathione, glycaemia and lipids in Type 2 diabetes.
Plasma homocysteine is an established risk factor for vascular disease and precursor of the anti-oxidant glutathione. This study was designed to investigate the relationship of changes in homocysteine (Hcy) induced by oral folate to glutathione and measures of glycaemia and lipid metabolism in Type 2 diabetes (T2DM). Twenty-seven patients (26 male, 1 female, aged 48-68 years) with T2DM and microalbuminuria were treated with folic acid 10 mg daily for 3 months. During the study, diastolic blood pressure (p=0.04), HbA1c (p=0.04), serum triglycerides (p=0.04) and serum total/HDL-cholesterol ratio (p=0.004) all increased and serum HDL-cholesterol fell (p=0.006). The increased red cell folate correlated with a reduction in microalbuminuria (p=0.001). Overall, plasma glutathione increased (p=0.016) despite reduction in its precursor Hcy (p<0.001). Change in glutathione correlated inversely with change in HbA1c (p<0.02), total cholesterol (p=0.003) and triglycerides (p<0.02) and positively with HDL-cholesterol (p=0.033). Increase in glutathione correlated with levels of vitamin B6 (p<0.05). Metformin treatment protected against the rise in blood pressure (BP) (p=0.02), independently of changes in plasma glutathione. In summary, oral folic acid supplementation in T2DM reduced plasma Hcy and increased glutathione levels. HbA1c, triglycerides and HDL-cholesterol deteriorated during the trial: their levels correlated inversely with changes in glutathione. The increase in glutathione may depend on an adequate supply of B6, as changes in glutathione correlated with vitamin B6 levels. Reduced Hcy and increased glutathione may both mediate improvement in vascular function and outcome. Some aspects of the response to folate may be different in patients on metformin.


Inelastic tunneling spectroscopy of alkanethiol molecules: high-resolution spectroscopy and theoretical simulations.
We investigate inelastic electron tunneling spectroscopy (IETS) for alkanethiol self-assembled monolayers (SAM) with a scanning tunneling microscope and compare it to first-principles calculations. Using a combination of partial deuteration of the molecule and high-resolution measurements, we identify and differentiate between methyl (CH3) and methylene (CH2) groups and their symmetric and asymmetric C-H stretch modes. The calculations agree quantitatively with the measured IETS in producing the weight of the symmetric and asymmetric C-H stretch modes while the methylene stretch mode is largely underestimated. We further show that inelastic intermolecular scattering is important in the SAM by plotting the theoretical current densities.


Microbial canthaxanthin: an orange-red keto carotenoid with potential pharmaceutical applications.
Canthaxanthin is an orange-red keto-carotenoid that occurs naturally and is also manufactured by synthetic methods for regular applications. In nature, canthaxanthin mainly exists in microbes such as different bacterial species, fungi, and algae, as well as in animals such as crustaceans, certain fishes, and birds. However, the amount of canthaxanthin produced in these organisms varies significantly. Additionally, the compound can be generated from genetically modified organisms using genetic engineering techniques Canthaxanthin finds extensive application as an additive in animal feed, in the pharmaceutical industry, as a coloring agent for various food products, and in cosmetics. It has powerful antioxidant properties and plays a role in lipid metabolism, neuroprotection, and immunomodulation. This article gives an extensive insight into the structure and methods of synthesis of canthaxanthin along with its various newly discovered sources identified so far. The significant applications of canthaxanthin, particularly its role in pharmaceuticals, are critically evaluated. Furthermore, the article discusses future aspects and challenges associated with canthaxanthin production and regulation.


Standing Blood Pressure and Risk of Falls, Syncope, Coronary Heart Disease, and Mortality.
ACC/AHA guidelines caution against the use of antihypertensive therapy in the setting of low standing systolic BP (SBP) < 110 mm Hg due to unclear benefits. The Atherosclerosis Risk in Communities (ARIC) Study measured supine and standing SBP in adults aged 45-64 years between 1987 and 1989. We used Cox regression to evaluate the associations of low standing SBP (<110 mm Hg) with risk of falls, syncope, coronary heart disease (CHD), and mortality through December 31, 2019. Falls and syncope were ascertained by hospitalization and outpatient claims; CHD events were adjudicated. Associations were examined overall and in strata of hypertension stage, 10-year atherosclerotic cardiovascular disease (ASCVD) risk, age, and sex. Among 12,467 adults followed a median of 24 years (mean age at enrollment 54.1 ± 5.8 years, 55% women, 26% Black adults), 3,000 (24%) had a standing SBP < 110 mm Hg. A standing SBP < 110 mm Hg compared to standing SBP ≥ 110 mm Hg was not significantly associated with falls or syncope, and was associated with a lower risk of CHD events and mortality with HRs of 1.02 (95% CI 0.94, 1.11), 1.02 (0.93, 1.11), 0.88 (0.80, 0.97), and 0.91 (0.86, 0.97), respectively. There were no clinically meaningful differences when stratified by hypertension stage, 10-year ASCVD risk, age, and sex. In this community-based population, low standing SBP was common and not significantly associated with falls or syncope, but was associated with a lower risk of CHD and mortality. These findings do not support screening for low standing BP as a risk factor for adverse events.


Is It Correct to Consider Caustic Ingestion as a Nonviolent Method of Suicide? A Retrospective Analysis and Psychological Considerations.
Suicide methods chosen by victims are particularly critical in suicide risk research. To differentiate suicide deaths, it is usual to categorize them as violent and nonviolent depending on the detrimental method chosen by the victims. Caustic ingestion, for example, is traditionally considered as a nonviolent suicide method. It results in severe consequences for the human body and it is associated with high levels of lethality. In this study, we retrospectively analyzed suicides that occurred between 1993 and 2021 in Milan (Italy) and that underwent autopsy. We compared a sample of 40 victims that ingested caustic substances with a sample of 460 victims of other chemical ingestion, and a sample of 3962 victims from violent suicide. Univariate analyses and univariate logistic regression models were performed. Suicides from caustic poisoning were significantly older, had a higher mean number of diseases and were more affected by psychiatric diseases compared to other chemical ingestion victims. By contrast, caustic suicides, compared to violent suicides, had a more balanced gender ratio, a higher mean number of diseases, were more affected by psychiatric diseases, had a higher rate of complex suicides (more than one modality), and had victims who died more frequently inside instead of outside. In logistic regression models, age was the only feature differentiating caustic from other chemical ingestion suicides while the features differentiating caustic from violent suicides were gender, mean number of diseases and suicide place. Suicides by caustic ingestion showed substantial differences compared to violent suicides, with a higher severe profile. However, some differences were reported comparing caustic ingestion to other chemical ingestion as well. Thus, we argue whether it is more appropriate to differentiate the suicidal ingestion of caustics from both violent and nonviolent suicide methods.


Deconvoluting Lipid Nanoparticle Structure for Messenger RNA Delivery.
Lipid nanoparticle (LNP) packaged mRNA vaccines have been deployed against infectious diseases such as COVID-19, yet their structural features remain unclear. Cholesterol, a major constituent within LNPs, contributes to their morphology that influences gene delivery. Herein, we examine the structure of LNPs containing cholesterol derivatives using electron microscopy, differential scanning calorimetry, and membrane fluidity assays. LNPs formulated with C24 alkyl derivatives of cholesterol show a polymorphic shape and various degrees of multilamellarity and lipid partitioning, likely due to phase separation. The addition of methyl and ethyl groups to the C24 alkyl tail of the cholesterol backbone induces multilamellarity (>50% increase compared to cholesterol), while the addition of a double bond induces lipid partitioning (>90% increase compared to cholesterol). LNPs with multilamellar and faceted structures, as well as a lamellar lipid phase, showed higher gene transfection. Unraveling the structure of mRNA-LNPs can enable their rational design toward enhanced gene delivery.


Suicide prevention in depressed women.
This paper focuses on risk factors and clinical states associated with suicide in depressed women and the necessity for thorough clinical evaluation of family and personal histories of suicidal, impulsive, and violent behaviors. Treatment issues addressed include the importance and content of detailed communication to patients and their families, medication noncompliance, the risks associated with the recovery and other high-risk periods, and problems associated with the adjunctive use of alcohol and other drugs.


Dibenzo[a,c]phenazine: a polarity-insensitive hydrogen-bonding probe.
A derivative of phenazine, dibenzo[a,c]phenazine (DBPZ), can be used as a very good hydrogen-bonding probe unlike its parent phenazine molecule. Steady-state absorption and fluorescence studies reveal that DBPZ is completely insensitive to polarity of the medium. However, DBPZ can form a hydrogen bond very efficiently in its first excited singlet state. The extent of this excited-state hydrogen-bond formation depends both on size and on hydrogen-bond donor ability of the solvents. Time-resolved fluorescence studies and theoretical calculations also suggest that this hydrogen-bond formation is much more favorable in the excited state as compared to the ground state. In the excited state, the electron density is pushed toward the nitrogen atoms from the benzene rings, thereby increasing the dipole moment of the DBPZ molecule. Although the dipole moment of DBPZ increases upon photoexcitation, like other polarity probes, the molecule remains fully insensitive to the polarity of the interacting solvent. This unusual behavior of DBPZ as compared to simple phenazine and other polarity probes is due to the structure of the molecule. Hydrogen atoms at the 1 and 8 positions of DBPZ are sterically interacting with a lone pair of electrons on the proximate nitrogen atoms and make both of the nitrogen atoms inaccessible to solvent molecules. For this reason, DBPZ cannot sense the polarity of the medium. However, DBPZ can only sense solvents, those that have hydrogen with some electropositive nature, that is, the hydrogen-bond donating solvents. Hydrogen being the smallest among all elements can only interact with the lone pair of electrons of nitrogen atoms. Thus, DBPZ can act as a sensor for the hydrogen-bond donating solvents irrespective of their dielectrics.


Ultrasound for ovarian cancer screening: are we throwing the baby out with the bath water?
The lack of standardization in gynaecological scanning is worrying, especially with regard to the sonographic evaluation of adnexal masses. The results of ongoing trials on the use of ultrasound as a screening test for ovarian cancer are likely to be affected by this lack of standardization in terminology and classifications. The lack of high-quality gynaecological ultrasound, combined with the low prevalence of ovarian cancer, may yield to a poor performance of transvaginal ultrasound as a screening test for ovarian cancer in large trials. In order to increase the specificity of ultrasound in a screening program, thus reducing unnecessary surgeries, a uniform, reproducible and accurate method for the sonographic evaluation of ovarian masses must be implemented. This move to improve and standardize reporting in gynaecological ultrasound should negate the need to use the phrase 'complex ovarian mass'. In this paper, we will critically evaluate current terminology, newly proposed accepted morphological classification of ovarian cysts as well as the ability for ultrasound to discriminate between benign and malignant ovarian masses.


The Impact of the COVID-19 Pandemic on Health, Quality of Life and Intrafamilial Relations - A Population-Based Survey in Germany.
The occurrence of the novel severe acute respiratory syndrome coronavirus-2 (COVID-19) at the end of 2019 comes along with many challenges. Besides worry for one's own health and the well-being of the family, all measures applied to limit the spread of the coronavirus affected daily life. School closures, economic shutdown and contact restrictions have led to high levels of stress. The impact on health and families has been widely discussed. However, population-based data are scarce. Here, we have assessed health, quality of life and intrafamilial relations depending on the COVID-19 pandemic. Using a three-step random-route approach, a population-based sample of 2,515 persons (52.6% female, average age of 50.3 years) was recruited during the second COVID-19 wave in Germany in winter 2020/21. While the majority of participants reported no change in their health status and the relationship with their partner and children, more than half of participants reported a decreased quality of life since the beginning of the pandemic. Female gender, age above 60 years, a low household income, not living with a partner and the experience of childhood adversity were associated with a higher risk for a worsening of health, quality of life and intrafamilial relations. These had already been well-established risk factors ahead of the pandemic. In order to avoid further increase of inequality in our society and more devastating impact of the pandemic on health and intrafamilial relations, low-level support and intervention programs are urgently needed.


On avoided words, absent words, and their application to biological sequence analysis.
The deviation of the observed frequency of a word w from its expected frequency in a given sequence x is used to determine whether or not the word is avoided. This concept is particularly useful in DNA linguistic analysis. The value of the deviation of w, denoted by [Formula: see text], effectively characterises the extent of a word by its edge contrast in the context in which it occurs. A word w of length [Formula: see text] is a [Formula: see text]-avoided word in x if [Formula: see text], for a given threshold [Formula: see text]. Notice that such a word may be completely absent from x. Hence, computing all such words naïvely can be a very time-consuming procedure, in particular for large k. In this article, we propose an [Formula: see text]-time and [Formula: see text]-space algorithm to compute all [Formula: see text]-avoided words of length k in a given sequence of length n over a fixed-sized alphabet. We also present a time-optimal [Formula: see text]-time algorithm to compute all [Formula: see text]-avoided words (of any length) in a sequence of length n over an integer alphabet of size [Formula: see text]. In addition, we provide a tight asymptotic upper bound for the number of [Formula: see text]-avoided words over an integer alphabet and the expected length of the longest one. We make available an implementation of our algorithm. Experimental results, using both real and synthetic data, show the efficiency and applicability of our implementation in biological sequence analysis. The systematic search for avoided words is particularly useful for biological sequence analysis. We present a linear-time and linear-space algorithm for the computation of avoided words of length k in a given sequence x. We suggest a modification to this algorithm so that it computes all avoided words of x, irrespective of their length, within the same time complexity. We also present combinatorial results with regards to avoided words and absent words.


Effects of corticotropin releasing factor on the production of adrenocorticotropic hormone by leukocyte populations.
1. Corticotropin-releasing factor (CRF), a neuropeptide with immunomodulating properties, is known to stimulate avian splenic leukocytes to produce adrenocorticotropic hormone (ACTH). 2. The present study was to determine which avian splenic leukocyte subpopulation(s) produce ACTH in response to CRF stimulation. 3. Splenic leukocytes from 8-week-old male chickens were isolated on Histopaque 1077 and macrophages were separated from lymphocytes by adherence to a polystyrene surface. 4. Different concentrations of CRF (0, 5, 50, 500 or 1000 ng/m) were incubated with the different leukocyte populations, supernatants were collected and ACTH was measured using a radioimmunoassay. 5. Isolated macrophages, stimulated with CRF, produced significantly more ACTH than either unstimulated macrophages or CRF-stimulated lymphocytes, suggesting that ACTH may be produced by a particular subset of leukocytes, the macrophages (and monocytes), in response to CRF stimulation.


Urinary and Serum Metabolomics Analyses Uncover That Total Glucosides of Paeony Protect Liver against Acute Injury Potentially via Reprogramming of Multiple Metabolic Pathways.
Total glucosides of paeony (TGP) have been confirmed to be hepatoprotective. However, the underlying mechanism is largely unclear. In this study, we investigated the metabolic profiles of urine and serum in rats with carbon tetrachloride- (CCl4-) induced experimental liver injury and TGP administration by using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The vehicle or a single dose of TGP was intragastrically administered to Wistar rats once a day for 14 consecutive days. To induce ALI, 50% CCl4 was injected intraperitoneally into these rats 2 hours after the last time administration of saline of TGP at the 14th day. The results indicated that TGP administration could protect rats from CCl4-induced ALI and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation, as well as hepatocyte apoptosis and inflammation. Furthermore, metabolomics analysis showed that TGP treatment significantly attenuated CCl4-triggered deregulation of multiple metabolites in both urine and serum, including glycine, alanine, proline, and glutamine. Metabolite set enrichment and pathway analyses demonstrated that amino acid cycling and glutathione metabolism were two main pathways involved in CCl4-induced experimental liver injury and TGP administration. Taken together, these findings revealed that regulation of metabolites potentially plays a pivotal role in the protective effect of TGP on ALI.


Bioprocessing of baculovirus vectors: a review.
The baculovirus/insect cell expression system is best known, and used, as a research tool for the production of recombinant proteins often requiring post-translational modifications. Although studies on the larger scale use of the system have been reported on for three decades, the recognition of this system as an industrially relevant platform for the production of biologics has only been recently achieved with the approvals of baculovirus-derived human and veterinary vaccines for commercialization. The full utility of baculoviruses, however, does not end with the production of recombinant proteins; baculoviruses are increasingly being studied for their ability to transduce mammalian cells and use as a therapeutic themselves. There is, therefore, a need to revisit the current state of the art in the bioprocessing of baculoviruses as the product. This paper is an extensive review of what is currently known about the amplification and recovery of baculoviruses and highlights the gaps that have not been focused on in the midst of optimizing this system for protein production.


Dose relationship between GnRH antagonists and pituitary suppression.
While the clinical significance of gonadotrophin-releasing hormone (GnRH) agonists is well recognized, the potential use of GnRH antagonists in humans awaits the availability of potent analogues with no untoward side-effects. We have designed, synthesized and tested several hundred linear and cyclic analogues (agonists and antagonists) of GnRH in different rat models; some have high histamine releasing activity and others have poor solubility in aqueous buffers with a pH > 6.0. Furthermore, we have identified analogues exhibiting short (< 12 h), intermediate (12-72 h) and long (> 72 h) duration of action in the rat (50 micrograms s.c. dose/rat). We have concluded that the basis for such resistance to degradation and elimination must be specific. In order to gain further information on the optimal nature and sterical requirements of side-chains, preliminary experiments were carried out using betidamino acids. Finally, mono- and dicyclic analogues of GnRH with potencies comparable with that of the most potent linear analogues were also obtained. Our approach to the development of such analogues included the use of nuclear magnetic resonance and computational techniques as well as that of state-of-the-art synthetic approaches. We intend to use the information derived from these structure/activity relationship studies to design conformationally-similar peptido-mimetics.


Healthcare Providers' Knowledge and Attitude Towards Abortions in Thailand: A Pre-Post Evaluation of Trainings on Safe Abortion.
Although physicians in Thailand can carry out abortions legally, unsafe abortion rates remain high and have serious consequences for women's health. Training programs for healthcare providers on the 'Care of unplanned and adolescent pregnancies for the prevention of unsafe abortions' have been implemented in Thailand with the aim of providing information and challenging negative attitudes about abortions. This study investigated the participants of the training courses in order to: (i) evaluate their knowledge and attitudes towards safe abortions; and (ii) investigate the factors that determine their knowledge and attitudes. A pre-post study design was applied. Descriptive statistics were calculated to provide an overview of the data. Bivariate analysis, a Wilcoxon signed rank test and a multivariable analysis using multiple linear regression were applied to determine the changes in attitudes and assess the likelihood of behaviour change towards adolescents and women experiencing unplanned pregnancy and abortions, according to demographic and professional characteristics. Having had the training, healthcare providers' change in attitudes towards adolescents and women experiencing unplanned pregnancies and abortions were found to be 0.67 points for the nine responses of attitudes and 0.79 points for the 14 responses on various abortion scenarios. Changes in attitude were significantly different among the varying health professional types, with non-doctors increasing by 0.53 points, non-obstetricians and non-gynaecologists increasing by 0.46 points and obstetricians and gynaecologists (OBGYN) increasing by 0.32 points. Positive attitudes towards unplanned pregnancies and unsafe abortions and attitudes towards abortion scenarios significantly increased. The career type of the health professional was a significant factor in improving attitudes. The training program was more effective among non-doctor healthcare providers. Therefore, non-doctors could be the target population for training in the future.


Does metoclopramide exposure alter endometrial receptivity and decrease pregnancy rates?
The aim of this study was to investigate the effect of metoclopramide on endometrial receptivity with an immunohistochemical investigation of integrin β3 expression in pregnant rats. In the present study, the pregnant mice administrated by different doses of metoclopramide were used to explore the effect of metoclopramide on embryo implantation, especially on the endometrial receptivity. The statistical results showed that the number of implanted embryos was gradually declining along the increasing dose of metoclopramide. When the administrated dose of metoclopramide was 3 mg/kg per day, great changes were observed in the exposed uterine morphology and down-regulated integrin β3 were also found in high dose metoclopramide-exposed mice. Metoclopramide exposure, especially in high doses may alter endometrial receptivity by effecting integrin expression on decidual tissue which can decrease pregnancy rates. This drug should only be recommended for use during pregnancy when benefit outweighs the risk.


Development of a UV laser-induced fluorescence lidar for monitoring blue-green algae in Lake Suwa.
We developed a UV (355 nm) laser-induced fluorescence (LIF) lidar for monitoring the real-time status of blue-green algae. Since the fluorescence spectrum of blue-green algae excited by 355 nm showed the specific fluorescence at 650 nm, the lidar was designed to be able to detect the 650 nm fluorescence as a surveillance method for the algae. The usefulness was confirmed by observation at Lake Suwa over four years (2005-2008). The detection limit of the LIF lidar was 16.65 mg/L for the blue-green algae, which is the range of concentrations in the safe level set by the World Health Organization.


Regulation of neuropeptide release.
The demonstration of depolarization-induced release of substance P, Met- and Leu-enkephalin, somatostatin, neurotensin, vasoactive intestinal polypeptide and cholecystokinin-like material from various regions of rat brain in vitro supports the hypothesis that these and other neuropeptides may act as neurotransmitters. In each case the stimulus-evoked release, but not the basal release, of peptide was dependent on the presence of calcium ions in the external medium. The stimulus-evoked release of substance P from nerve terminals in rat substantia nigra may be regulated by presynaptic gamma-aminobutyric acid (GABA) receptors. The possible existence of presynaptic opiate receptors on substance P-containing sensory nerve terminals may offer an explanation for the analgesic effects of opiates at spinal cord level, and for the existence of enkephalin neurons in substantia gelatinosa. Capsaicin releases substance P from spinal cord nerve terminals and may impair their function, while having no effect on substance P neurons in supraspinal regions. The possibility of cosecretion of peptide and amine products from the same cells is discussed.


Comparison of mouth rinsing performance between adults and children using a contactless vital sensing camera.
Evaluating mouth rinsing skills is useful for assessing oral function, however current evaluation methods are subjective. This study compared mouth rinsing between adults and children using a contactless camera to capture lip motion. The subjects comprised 16 adults and 13 children with no oral dysfunction. A compact vital sensing camera adapted from a Microsoft Xbox One Kinect Sensor® (Kinect) was placed 100 cm from the floor and 120 cm from the subject; 5, 10 and 15 ml of water were used as samples. Participants were instructed to hold the sample in the oral cavity, close the lips and move the sample alternatively left and right for 15 s. Maximum/minimum displacement from the reference plane and rinsing cycle for each sample were analysed by one-way analysis of variance. In adults, there was no significant difference in the maximum/minimum displacement between the left and right sides of the angulus oris due to differences in sample amount. In children, the right maximum significantly differed between the 5- and 15-ml and 10- and 15-ml samples, while the left maximum significantly differed between the 5- and 10-ml and 5- and 15-ml samples. The right minimum significantly differed between the 5- and 10-ml samples, as did the duration of mouth rinsing between the 5- and 15-ml samples. In children, lip movement and mouth rinsing duration tended to decrease with increasing sample volume. Evaluating lip movement using a contactless vital sensing camera is useful for assessing children's development of oral function.


Sox9 Increases the Proliferation and Colony-forming Activity of Outer Root Sheath Cells Cultured In Vitro.
β-catenin plays a pivotal role in hair follicle development and hair growth cycle. The aim of this study was to identify β-catenin-regulated genes in cultured human hair outer root sheath (ORS) cells. Primary cultured ORS cells were transduced with recombinant adenovirus expressing N-terminal truncated β-catenin (constitutive active form), and β-catenin-regulated genes were identified. Overexpression of the constitutively active form of β-catenin led to induction of Sox9 expression at both mRNA and protein levels. To investigate the potential role of Sox9, we made the recombinant adenovirus expressing green fluorescent protein-tagged Sox9, and then transduced into cultured ORS cells. Interestingly, Sox9 induced the expression of keratin 15, increased the proliferation of ORS cells in vitro, and enhanced colony-forming activity. Our results suggest that Sox9 is a β-catenin-regulated gene in ORS cells, and has potential importance in the regulation of hair follicle homeostasis.


A commentary on the animal welfare symposium, with possible actions.
The author analyzes the common themes addressed by speakers at the AVMA/AAVMC conference on animal welfare, adding a few comments of his own. These themes can be summarized in the basic statement that "the veterinary profession has a responsibility to its members and to the public to provide and ensure a good education in animal welfare science, ethics, and public policy and law." Veterinarians have a special role as animals' advocates for several reasons: they have the knowledge base and the required skills and commitment to fulfill this role; they have earned the confidence and respect of the constituents they serve; they are the professionals to whom policy makers logically turn for guidance on animal health and welfare issues. Therefore, the veterinary profession has an opportunity to reassert itself as the advocate not only for animals' physical health but also for their mental health and welfare. To be successful, however, the profession's leadership and members must engage without delay in advancing educational programs, research projects, and outreach to solidify authority in this key component of veterinary medicine.


eIF3-f function in skeletal muscles: to stand at the crossroads of atrophy and hypertrophy.
The control of muscle cell size is a physiological process balanced by a fine tuning between protein synthesis and protein degradation. MAFbx/Atrogin-1 is a muscle specific E3 ubiquitin ligase upregulated during disuse, immobilization and fasting or systemic diseases such as diabetes, cancer, AIDS and renal failure. This response is necessary to induce a rapid and functional atrophy. To date, the targets of MAFbx/Atrogin-1 in skeletal muscle remain to be identified. We have recently presented evidence that eIF3-f, a regulatory subunit of the eukaryotic translation factor eIF3 is a key target that accounts for MAFbx/Atrogin-1 function in muscle atrophy. More importantly, we showed that eIF3-f acts as a "translational enhancer" that increases the efficiency of the structural muscle proteins synthesis leading to both in vitro and in vivo muscle hypertrophy. We propose that eIF3-f subunit, a mTOR/S6K1 scaffolding protein in the IGF-1/Akt/mTOR dependent control of protein translation, is a positive actor essential to the translation of specific mRNAs probably implicated in muscle hypertrophy. The central role of eIF3-f in both the atrophic and hypertrophic pathways will be discussed in the light of its promising potential in muscle wasting therapy.


Medical decision-making and minors: issues of consent and assent.
The physician-patient relationship has been described as an egalitarian partnership in which patients and physicians work together to make healthcare decisions. Although adults receive considerable encouragement to become active participants in medical decision-making, children and adolescents often have little voice in such decisions and are granted limited access to confidential medical care. After a brief discussion of legal perspectives on informed consent, the present review examines the developmental literature on children and adolescents' capacities to make medical decisions that are informed, voluntary, and rational. The purposes and benefits of assent are identified. Remaining questions of how to evaluate capacity and balance parental and minor autonomy are explored.


[Treatment for cervical carotid artery stenosis using evidenced-based medicine].
While cervical carotid stenosis should be essentially treated with anti-thrombotic drugs, carotid endarterectomy (CEA) or carotid artery stenting (CAS) may be performed for such lesions when definite criteria are met. These criteria have been determined through several large controlled randomized trials. The benefit of CEA has been established by NASCET, ECST, ACAS, and ACST. The SAPPHIRE trial showed the non-inferiority of CAS compared to CEA in patients with high-risk factors for CEA. However, SPACE, EVA-3S, and ICSS failed to show this non-inferiority in patients without high risk factors for CEA. CREST, the most recent trial, has demonstrated that CAS and CEA are equally effective. In conclusion, CEA is the treatment of choice for patients with severe asymptomatic or symptomatic carotid artery stenosis. CAS should be performed for patients with severe carotid artery stenosis only when they have high-risk factors for CEA.


Need for Desire Drugs Debated.
Some see a big market for medications for low libido in women. But sales of Addyi have been slow. Has a normal experience been unnecessarily medicalized? One of many factors in the debate is whether women#x02019;s sexual response tends to be more spontaneous or responsive.