A resuscitation "dilemma" theory-practice-ethics. Is there a theory-practice-ethics gap?
The theory-practice-ethics gap - a new paradigm to contemplate. Practices based on tradition, rituals and outdated information are placed into a nonscientific paradigm called the theory-practice gap. Within this paradigm there is often a gap between theoretical knowledge and its application in practice. This theory-practice gap has always existed [Allmark, P., 1995. A classical view of the theory-practice gap in nursing. J. Adv. Nurs. 22 (1), 18-23; Hewison, A. et al., 1996. The theory-practice gap in nursing: a new dimension. J. Adv. Nurs. 24 (4), 754-761]. Its creation is often sited as a culmination of theory being idealistic and impractical, even if practical and beneficial, are often ignored. Most of the evidence relating to the non integration of theory and practice makes the assumption that environmental factors are responsible and will affect learning and practice outcomes, hence the "gap". In fact, it is the author's belief, that to "bridge the gap" between theory and practice an additional component is required, called ethics. A moral duty and obligation ensuring theory and practice integrate. In order to effectively implement new practices, one must deem these practices are worthy and relevant to their role as healthcare providers. Otherwise, we fall victims to providing nothing more than a lip service. This introduces a new concept which the author refers to as the theory-practice-ethics gap. This theory-practice-ethics gap must be considered when reviewing some of the unacceptable outcomes in health care practice. The author believes that there is a crisis of ethics where theory and practice integrate, and as a consequence, malfeasance. We are failing to fulfill our duty as healthcare providers and as patient advocates. One practice of major concern, which the author will endeavor to unfold relates to adult and pediatric resuscitation.


Identification of a retina-specific Otx2 enhancer element active in immature developing photoreceptors.
The homeodomain protein, Otx2, is a critical regulator of vertebrate photoreceptor genesis. However, the genetic elements that define the expression of Otx2 during photoreceptor development are unknown. Therefore, we sought to identify an Otx2 enhancer element that functions in photoreceptor development in order to better understand this specification event. Using the technique of electroporation, we tested a number of evolutionarily conserved elements (ECRs) for expression in the developing retina, and identified ECR2 as having robust activity in the retina. We have characterized this element using a number of assays, including Cre-fate mapping experiments. We found that ECR2 recapitulates expression/function of Otx2 primarily in newly postmitotic photoreceptor cells (PRs), as well as in a subset of retinal progenitor cells (RPCs). ECR2 was also found to be expressed in a subset of horizontal cells (HCs), in keeping with the role of Otx2 in HC development. Furthermore, we determined that the ECR2 element is not active in other Otx2-positive cells such as retinal bipolar cells (BPs), retinal pigmented epithelium (RPE), or the tectum, suggesting that the transcriptional networks controlling Otx2 expression in these cells are unique from those of developing PRs and HCs. These results reveal a distinct molecular state in dividing retinal cells and their newly postmitotic progeny, and provide genetic access to an early and critical transcriptional node involved in the genesis of vertebrate PRs.


Liver damage in patients with colony-stimulating factor-producing tumors.
We have demonstrated that colony-stimulating factor (CSF)-producing tumor cell lines produce not only CSF but also interleukin-1 (IL-1) and interleukin-6 (IL-6). Clinically, we have observed that patients bearing such tumors present with liver dysfunction and fever in addition to marked leukocytosis. The purpose of this study was to determine whether or not the liver damage was specifically related to CSF-producing tumors. Clinicopathologic examinations were performed in six autopsied patients with CSF-producing tumors. We also transplanted two tumor cell lines (KHC287 and CHU-2), which produce granulocyte (G)-CSF, IL-1, and IL-6, to nude mice. Of the six patients, five had G-CSF- and one had granulocyte/macrophage (GM)-CSF-producing tumors. IL-1 and IL-6 concentrations in plasma or culture supernatant were elevated in these patients. Biochemical examinations revealed high serum enzyme levels of the biliary system in contrast to normal or slight increases in transaminase levels in all patients studied. Serum direct bilirubin was elevated in five of the six patients. Three common pathologic changes of the liver were found: (1) focal necrosis associated with neutrophil infiltration in the centrilobular zones, (2) fibrous change and enlargement of the portal area associated with neutrophil infiltration, and (3) intrahepatic cholestasis. The same pathologic changes, except for cholestasis, were reproduced in the liver of mice transplanted with KHC287 or CHU-2. These results indicate that patients with CSF-producing tumors have characteristic liver damage, and suggest a new paraneoplastic syndrome of leukocytosis and liver damage.


Gender-specific influence of the chromosome 16 chemokine gene cluster on the susceptibility to Multiple Sclerosis.
Macrophage-derived chemokine (MDC/CCL22) plays a role in Experimental Autoimmune Encephalomyelitis (EAE), the animal model of Multiple Sclerosis (MS). MDC/CCL22 gene is part of a chemokine cluster, which includes also thymus and Activation-Regulated Chemokine (TARC/CCL17). The frequency of the C/T and C/A Single Nucleotide Polymorphisms (SNPs) in the promoter and coding sequence of CCL22 as well as the C/T SNP in the promoter of CCL17 were determined in 370 patients with Multiple Sclerosis (MS) compared with 380 controls. A trend towards a decreased allelic frequency of the A allele of the CCL22 C/A SNP as well as of the T allele of the CCL17 C/T SNP was found in patients compared with controls. The frequency of the AT haplotype was significantly decreased in MS patients (P=0.017, OR: 0.49, CI: 0.28-0.87). Stratifying patients according to gender, the observed association was even more pronounced in male patients compared with male controls (P=0.004, OR=0.18, 95% CI: 0.06-0.50), whereas no significant differences were observed in females. Therefore, the presence of the AT haplotype in chromosome 16 chemokine cluster is likely to confer a decreased risk of developing MS, particularly in males.


Evaluation of second-line apatinib plus irinotecan as a treatment for advanced gastric adenocarcinoma or gastroesophageal conjunction adenocarcinoma: a prospective, multicenter phase II trial.
Apatinib and irinotecan are used as systematic therapies for advanced gastric adenocarcinoma (GAC) and gastroesophageal junction adenocarcinoma (GEJA), while the evidence for their combination as second-line therapy in these patients is limited. This study aimed to evaluate the efficacy and safety of second-line apatinib plus irinotecan for the treatment of GAC and GEJA. In this prospective, multicenter phase II clinical study, 28 patients with advanced GAC or GEJA who received second-line apatinib plus irinotecan were recruited. In total, 1 (3.6%) patient achieved complete response, 7 (25.0%) patients achieved partial response, 13 (46.4%) patients had stable disease, and 4 (14.3%) patients showed progressive disease, while clinical response was not evaluable or not assessed in 3 (10.7%) patients. The objective response rate and disease control rate were 28.6% and 75.0%, respectively. Meanwhile, the median (95% confidence interval (CI)) progression-free survival (PFS) was 4.5 (3.9-5.1) months, and the median (95% CI) overall survival (OS) was 11.3 (7.4-15.1) months. By multivariate Cox regression analysis, male sex, liver metastasis, and peritoneal metastasis were independently associated with worse PFS or OS, while treatment duration ≥5 months was independently associated with better OS. In terms of the safety profile, 89.3% of patients experienced treatment-emergent adverse events of any grade, among which 82.1% of patients had grade 1-2 adverse events and 64.3% of patients had grade 3-4 adverse events. Apatinib plus irinotecan as second-line therapy achieves a good treatment response and satisfactory survival with tolerable safety in patients with advanced GAC or GEJA.


Repeated-sprint training in hypoxia boosts up team-sport-specific repeated-sprint ability: 2-week vs 5-week training regimen.
To investigate (1) the boosting effects immediately and 4 weeks following 2-week, 6-session repeated-sprint training in hypoxia (RSH2-wk, n = 10) on the ability of team-sport players in performing repeated sprints (RSA) during a team-sport-specific intermittent exercise protocol (RSAIEP) by comparing with normoxic counterpart (CON2-wk, n = 12), and (2) the dose effects of the RSH by comparing the RSA alterations in RSH2-wk with those resulting from a 5-week, 15-session regimen (RSH5-wk, n = 10). Repeated-sprint training protocol consisted of 3 sets, 5 × 5-s all-out sprints on non-motorized treadmill interspersed with 25-s passive recovery under the hypoxia of 13.5% and normoxia, respectively. The within- (pre-, post-, 4-week post-intervention) and between- (RSH2-wk, RSH5-wk, CON2-wk) group differences in the performance of four sets of RSA tests held during the RSAIEP on the same treadmill were assessed. In comparison with pre-intervention, RSA variables, particularly the mean velocity, horizontal force, and power output during the RSAIEP enhanced significantly immediate post RSH in RSH2-wk (5.1-13.7%), while trivially in CON2-wk (2.1-6.2%). Nevertheless, the enhanced RSA in RSH2-wk diminished 4 weeks after the RSH (- 3.17-0.37%). For the RSH5-wk, the enhancement of RSA immediately following the 5-week RSH (4.2-16.3%) did not differ from that of RSH2-wk, yet the enhanced RSA was well-maintained 4-week post-RSH (0.12-1.14%). Two-week and five-week RSH regimens could comparably boost up the effects of repeated-sprint training in normoxia, while dose effect detected on the RSA enhancement was minimal. Nevertheless, superior residual effects of the RSH on RSA appear to be associated with prolonged regimen.


Use of hand-to-hand impedancemetry to predict body composition of African women as measured by air displacement plethysmography.
To test the validity of a simple, rapid, field-adapted, portable hand-held impedancemeter (HHI) for the estimation of lean body mass (LBM) and percentage body fat (%BF) in African women, and to develop specific predictive equations. Cross-sectional observational study. Dakar, the capital city of Senegal, West Africa. A total sample of 146 women volunteered. Their mean age was of 31.0 y (s.d. 9.1), weight 60.9 kg (s.d. 13.1) and BMI 22.6 kg/m(2) (s.d. 4.5). Body composition values estimated by HHI were compared to those measured by whole body densitometry performed by air displacement plethysmography (ADP). The specific density of LBM in black subjects was taken into account for the calculation of %BF from body density. : Estimations from HHI showed a large bias (mean difference) of 5.6 kg LBM (P<10(-4)) and -8.8 %BF (P<10(-4)) and errors (s.d. of the bias) of 2.6 kg LBM and 3.7 %BF. In order to correct for the bias, specific predictive equations were developed. With the HHI result as a single predictor, error values were of 1.9 kg LBM and 3.7 %BF in the prediction group (n=100), and of 2.2 kg LBM and 3.6 %BF in the cross-validation group (n=46). Addition of anthropometrical predictors was not necessary. The HHI analyser significantly overestimated LBM and underestimated %BF in African women. After correction for the bias, the body compartments could easily be estimated in African women by using the HHI result in an appropriate prediction equation with a good precision. It remains to be seen whether a combination of arm and leg impedancemetry in order to take into account lower limbs would further improve the prediction of body composition in Africans.


Effects of recruiting maneuvers in patients with acute respiratory distress syndrome ventilated with protective ventilatory strategy.
A lung-protective ventilatory strategy with low tidal volume (VT) has been proposed for use in acute respiratory distress syndrome (ARDS). Alveolar derecruitment may occur during the use of a lung-protective ventilatory strategy and may be prevented by recruiting maneuvers. This study examined the hypothesis that the effectiveness of a recruiting maneuver to improve oxygenation in patients with ARDS would be influenced by the elastic properties of the lung and chest wall. Twenty-two patients with ARDS were studied during use of the ARDSNet lung-protective ventilatory strategy: VT was set at 6 ml/kg predicted body weight and positive end-expiratory pressure (PEEP) and inspiratory oxygen fraction (Fio2) were set to obtain an arterial oxygen saturation of 90-95% and/or an arterial oxygen partial pressure (Pao2) of 60- 80 mmHg (baseline). Measurements of Pao2/Fio2, static volume-pressure curve, recruited volume (vertical shift of the volume-pressure curve), and chest wall and lung elastance (EstW and EstL: esophageal pressure) were obtained on zero end-expiratory pressure, at baseline, and at 2 and 20 min after application of a recruiting maneuver (40 cm H2O of continuous positive airway pressure for 40 s). Cardiac output (transesophageal Doppler) and mean arterial pressure were measured immediately before, during, and immediately after the recruiting maneuver. Patients were classified a priori as responders and nonresponders on the basis of the occurrence or nonoccurrence of a 50% increase in Pao2/Fio2 after the recruiting maneuver. Recruiting maneuvers increased Pao2/Fio2 by 20 +/- 3% in nonresponders (n = 11) and by 175 +/- 23% (n = 11; mean +/- standard deviation) in responders. On zero end-expiratory pressure, EstL (28.4 +/- 2.2 vs. 24.2 +/- 2.9 cm H2O/l) and EstW (10.4 +/- 1.8 vs. 5.6 +/- 0.8 cm H2O/l) were higher in nonresponders than in responders (P < 0.01). Nonresponders had been ventilated for a longer period of time than responders (7 +/- 1 vs. 1 +/- 0.3 days; P < 0.001). Cardiac output and mean arterial pressure decreased by 31 +/- 2 and 19 +/- 3% in nonresponders and by 2 +/- 1 and 2 +/- 1% in responders (P < 0.01). Application of recruiting maneuvers improves oxygenation only in patients with early ARDS who do not have impairment of chest wall mechanics and with a large potential for recruitment, as indicated by low values of EstL.


Needle-knife sphincterotomy guided by a biliary endoprosthesis in Billroth II gastrectomy patients.
All available techniques for performing endoscopic sphincterotomy in Billroth II gastrectomy patients have their limitations, and no standard technique has emerged. A new technique, needle-knife sphincterotomy guided by a thin (7 Fr) biliary endoprosthesis, is described here that overcomes some of the limitations of other techniques. The technique was attempted in 19 nonselected patients during a three-year period. The results were retrospectively assessed. The outcome variables were the achievement of an adequate sphincterotomy and complications. An adequate sphincterotomy could be performed without much technical difficulty in 18 of the 19 patients. There was one complication, a retroperitoneal leakage, that settled with conservative treatment. In patients with Billroth II anastomoses, endoprosthesis-guided sphincterotomy is a new and relatively easy procedure, which is especially attractive once selective bile duct cannulation has been achieved. This technique allows the performance of sphincterotomy as a well-controlled procedure, and may, therefore, be safer than nonguided techniques. In contrast to previously reported guided techniques using nasobiliary cannulas, the endoprosthesis technique does not necessitate withdrawing and reinserting the endoscope.


Importance of the Occipitoaxial Angle and Posterior Occipitocervical Angle in Occipitocervical Fusion.
To observe the effects of occipitoaxial angle (O-C2 angle, OC2A) and posterior occipitocervical angle (POCA) selection on postoperative clinical efficacy and lower cervical curvature in patients with acute acquired atlantoaxial dislocation after occipitocervical fusion (OCF). A total of 150 healthy subjects without cervical disease (healthy group) were randomly selected based on gender and age. Three spine surgeons measured the OC2A and POCA of the healthy group and averaged the values. A total of 30 patients with an average age of 51.0 years (range, 18-70 years; 16 male and 14 female) with trauma or rheumatoid arthritis (disease group) who underwent occipitocervical fusion (OCF) for atlantoaxial dislocation between January 2012 and June 2016 were reviewed. OC2A, POCA, and cervical spinal angle (CSA) were measured postoperative/soon after surgery and ambulation, and at the final follow-up visit. The preoperative and final follow-up visual analog scale (VAS), Japanese orthopedics association score (JOA), neck disability index (NDI), and dCSA (change of CSA from postoperative/soon after surgery and ambulation to final follow-up) were recorded. The values of OC2A and POCA in 150 healthy subjects were 14.5° ± 3.7° and 108.2° ± 8.1°, respectively, and the 95% confidence interval (CI) were 7.2°-21.8° and 92.3°-124.0°, respectively. There was a negative correlation between OC2A and POCA (r = -0.386, P < 0.001). There were 18 patients (group one) of ideal OC2A and POCA (both within 95% CI of the healthy group) postoperative/soon after surgery and ambulation with a mean follow-up time of 26.3 ± 20.9 months in disease group. The remaining patients (group two) with a mean follow-up time of 31.3 ± 21.3 months. There was no statistically significant difference in the baseline data as well as pre-operative outcomes, including VAS score, JOA score, and NDI between the two groups. Likewise, the post-operative outcomes in final follow-up, including VAS and JOA score, had no distinct difference in the two groups. However, NDI (11.0 ± 2.9) in group two at the final follow-up was significantly higher than that in group one (7.0 ± 2.3) (P < 0.001). And group two showed statistically greater dCSA (5.9 ± 7.5°) than group one (-2.3° ± 6.2°) (P = 0.003). The negative correlation between OC2A and POCA plays an important role in maintaining the biodynamic balance of the occipital-cervical region. OC2A and POCA should be controlled of a normal population in patients with acute acquired atlantoaxial dislocation during OCF, which can further improve the clinical efficacy and prevent loss of lower cervical curvature after surgery.


Isotretinoin and neuropsychiatric side effects: Continued vigilance is needed.
Isotretinoin (13-cis-retinoic acid, marketed under the names Accutane, Roaccutane, and others) is an effective treatment for acne that has been on the market for over 30 years, although reports of neuropsychiatric side effects continue to be reported. Isotretinoin is an isomer of the active form of Vitamin A, 13-trans-retinoic acid, which has known psychiatric side effects when given in excessive doses, and is part of the family of compounds called retinoids, which have multiple functions in the central nervous system. The literature was reviewed in pubmed and psychinfo for research related to isotretinoin and neuropsychiatric side effects including depression, suicidal thoughts, suicide, mania, anxiety, impulsivity, emotional lability, violence, aggression, and psychosis. Multiple case series have shown that successful treatment of acne with isotretinoin results in improvements in measures of quality of life and self esteem However, studies show individual cases of clinically significant depression and other neuropsychiatric events that, although not common, are persistent in the literature. Since the original cases of depression were reported to the United States Food and Drug Administration, numerous cases have been reported to regulatory agencies in the United Kingdom, France, Ireland, Denmark, Australia, Canada, and other countries, making isotretinoin one of the top five medications in the world associated with depression and other neuropsychiatric side effects. Clinicians are advised to warn patients of the risks of neuropsychiatric side effects with isotretinoin which may arise from the medication itself, and not just as a side effect of acne or youth.


Cross-Modal Perceptual Organization in Works of Art.
This study investigates the existence of cross-modal correspondences between a series of paintings by Kandinsky and a series of selections from Schönberg music. The experiment was conducted in two phases. In the first phase, by means of the Osgood semantic differential, the participants evaluated the perceptual characteristics first of visual stimuli (some pictures of Kandinsky's paintings, with varying perceptual characteristics and contents) and then of auditory stimuli (musical excerpts taken from the repertoire of Schönberg's piano works) relative to 11 pairs of adjectives tested on a continuous bipolar scale. In the second phase, participants were required to associate pictures and musical excerpts. The results of the semantic differential test show that certain paintings and musical excerpts were evaluated as semantically more similar, while others were evaluated as semantically more different. The results of the direct association between musical excerpts and paintings showed both attractions and repulsions among the stimuli. The overall results provide significant insights into the relationship between concrete and abstract concepts and into the process of perceptual grouping in cross-modal phenomena.


A facile and patternable method for the surface modification of carbon nanotube forests using perfluoroarylazides.
A facile patterning method for the functionalization of vertically aligned carbon nanotubes is described. Modification of the surface of nanotube forests with hydrophilic, hydrophobic, or polymerizable small molecules was achieved via UV-triggered attachment of perfluoroarylazides. Multiple functionalizations of the tube surface can be achieved. Macro- and micropatterning of forest substrates were demonstrated. Superhydrophobic surfaces containing superhydrophilic regions were prepared.


Female alcoholics: III. Patterns of consumption 3-10 years after treatment.
In a follow-up study of 55 female alcoholics, 44 women (80%) were interviewed on an average of 6.5 years after treatment. According to the reported quantity and frequency of drinking the year prior to follow-up, eight women (18%) were classified as abstainers, nine (20%) as light drinkers, ten (22%) as moderate drinkers, and 17 (39%) as heavy drinkers. In a longitudinal perspective, four main patterns of outcome could be discriminated: long-term abstinence, short-term abstinence intermingled with drinking, asymptomatic drinking and continuous heavy drinking. Most of the asymptomatic drinkers reported a consumption of very small amounts of alcohol, avoiding becoming intoxicated. Those women who reported consumption of more than 2/3 of a bottle of spirits on any single drinking day or consumed more than 7 liters of pure alcohol annually, usually satisfied the DSM-III criteria for alcohol abuse or alcohol dependence.


Mechanisms of mucus release in exposed canine gastric mucosa.
Mucus release was studied in the exposed gastric mucosa of anesthetized fasted dogs using scanning and transmission microscopy as well as histochemical and autoradiographic techniques. Under unstimulated conditions, the gastric epithelium was composed of both nonsecreting and mucus-secreting epithelial cells, with the former being predominant. Nonsecreting cells were characterized by an intact apical mucus package of granules and a continuous plasma membrane. The secreting mucus cell population was found in the foveolar (pit region) as well as interfoveolar areas. Three mechanisms of mucus release were observed: (a) exocytosis, (b) apical expulsion, and (c) cell exfoliation. Evidence for exocytosis was found in all mucus cells, especially in the sulfated glycoprotein-rich foveolar cells. Exocytosis involved only a few granules at a time; this mode of secretion is likely slow and continuous. In contrast, apical expulsion resulted in an explosive release of the entire apical mucus package followed by in situ degeneration of the cell itself. This occurred in the oldest cells forming mucosal crests in the interfoveolar area, whose mucus predominantly stains for neutral glycoproteins. Cell exfoliation, in which the entire cell was extruded into the lumen, was rarely observed and may provide, in addition to apical expulsion, a second mechanism to rid the mucosa of senescent epithelial cells. Mucus secretion is a complex function of the gastric epithelium. The mechanism of secretion and the histochemically defined type of mucus secreted are variables which are dependent on the age of the cell, its position on the foveolae, and the microenvironment within the gastric lumen. The mucus-containing surface and pit cells of gastric epithelium have been described morphologically and ultrastructurally in a number of studies. These cells are highly differentiated, forming a layer which is dynamic and responsive to conditions present in the gastric lumen. Mucus cells arise from multipotent progenitor cells which differentiate in the course of migration up the gastric pits and are involved in the complex macromolecular synthesis of glycoproteins. Although mucus release occurs throughout cell life, very little attention has been given to the cellular ultrastructural changes that deal with mucus secretion. As a result, the mucus-containing surface and pit cells have been described primarily in terms of their nonsecreting functional state. Exceptions to this are a few transmission and scanning electron microscopy studies which describe loss of intact mucus granules, cell extrusion, and in situ degeneration. These previous ultrastructural studies describe cellular patterns, in both normal and injured mucosa, which we fell are related to mucus release. Because of a paucity of knowledge concerning the normal mechanisms of mucus secretion, it was the purpose of this study to define the ultrastructural changes which result in and accompany the production of mucus in canine gastric epithelium.


Anatomy of the antennal dorsal organ in female of Neodryinus typhlocybae (Hymenoptera: Dryinidae): A peculiar sensory structure possibly involved in perception of host vibration.
Neodryinus typhlocybae (Hymenoptera: Dryinidae) is a natural enemy of the planthopper Metcalfa pruinosa, which was introduced from North America into Europe and has become established in various regions as a pest species. Vibrational signals play a crucial role in the communication of M. pruinosa, which appears to be exploited by N. typhlocybae. Scanning and transmission electron microscopy have shown that the antennae of N. typhlocybae females have peculiar and complex sensory structures: deep longitudinal grooves that house long sensilla trichodea, termed here "Antennal Dorsal Organs." Such structures were not present on male antennae. These sensilla extend for the length of the grooves, without contact with the groove cuticle. Their hair shaft is empty and aporous, and inserted into a specialized socket, underneath which there is a cuticular ampulla-like chamber. Each sensillum is associated with two sensory neurons: one terminates at the proximal end of the dendritic sheath; the other continues into the sensillum sinus and is enclosed in the dendritic sheath. This second sensory neuron then enters the ampulla-like chamber through the circular opening, and then terminates with a conspicuous tubular body at the shaft base. The possible involvement of this peculiar structure in the context of host recognition mechanism is discussed.


Accelerated Recovery Within Standardized Recovery Pathways After Esophagectomy: A Prospective Cohort Study Assessing the Effects of Early Discharge on Outcomes, Readmissions, Patient Satisfaction, and Costs.
After esophagectomy, some patients exceed targeted discharge goal within enhanced recovery after surgery programs. This study reviews the demographics, outcomes, cost, readmission rates, and patient satisfaction for the accelerated recovery (AR) group. Between 2010 and 2013, 137 consecutive esophagectomy patients were compared according to the length of hospital stay: AR 5 to 6 days, targeted recovery (TR) 7 to 8 days, and delayed recovery (DR) 9 days or more. The AR patients increased from 3% to 46% during the study period. The AR patients were younger, but all groups were comparable regarding comorbidities (Charlson, American Society of Anesthesiologists, and Eastern Cooperative Oncology Group score), cancer stage, and treatment approach. The AR patients were more likely to have neoadjuvant therapy, shorter operations, and less blood loss. The DR patients were more likely to have complications (40% AR versus 45% TR versus 90% DR, p < 0.001). Inhospital and 90-day mortality was 1.5%. All AR patients were discharged home (100% AR versus 87% TR versus 63% DR, p < 0.001), and 30-day readmission rates were comparable between groups (14% AR versus 19% TR versus 5% DR, p = 0.122). Overall mean costs ($38,385 AR versus $41,607 TR versus $61,199 DR, p < 0.001) as well as readmission costs ($7,470 AR versus $27,695 TR versus $33,398 DR, p = 0.202) were lower in the AR group. Patient satisfaction scores were comparable between groups. Accelerated recovery is achievable in a significant proportion of patients undergoing esophagectomy. Accelerated recovery is associated with decreased treatment costs but does not lead to increased readmissions or decreased patient satisfaction. Enhanced recovery after surgery programs should be designed to accommodate patients appropriate for AR.


Publication Trends of Research on Head and Neck Squamous Cell Carcinoma During 2002 to 2022: A 20-Year Bibliometric Study.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Our study attempted to analyze the research trends in HNSCC and compare contributions from different countries, institutions, journals, and authors. The authors extracted publications in this field from 2002 to 2022 from the Web of Science database. Microsoft Excel and VOSviewer were performed to collect data on publication numbers, analyze publication trends, and visualize relevant results. A total of 1903 publications were screened. In the past 20 years, the United States contributed the most publications and citations in the HNSCC research. China ranked second in the number of publications. The Ophthalmic Plastic and Reconstructive Surgery was the most productive journal concerning HNSCC. ESMAELIB of the University of Texas System and ROSENTHAL EL of Stanford University had published the most publications in this field. Keywords were categorized into 3 clusters: basic study, clinical feature study, and treatment-related study. The keywords "reflectance confocal microscopy", "raman-spectroscopy", and "confocal laser endomicroscopy" were most frequently emerged in the recent years. Management-related research has been recognized as a potential focus in the HNSCC.


[Influence of operation time point on the frequency of early complications after surgical femoral neck fracture treatment].
The current publication deals with surgically treated medial and lateral femoral neck fracture of patients aged 60 and older. All patients were evaluated who received operative treatment between day of trauma and day 14 after trauma. Therefore, 30,254 patients (77,44%) were included. All early complications observed during hospital treatment were recorded as general and special complications, and we calculated whether the day of operation influenced the occurrence of early complications. Statistically significant differences were gained for revision operations. If the primary operation was performed on days 2 to 3 or 4 to 5 after trauma, fewer revisions necessary. Similar results were gained for revisions due to seroma and haematoma or postoperative bleeding. In these cases, fewer revision operations were performed when primary treatment was achieved on day 2 or 3. From the data presented, it is postulated that early complications provide no decisive reason for treating femoral neck fracture as an emergency. However, considering late complications such as the rate of femoral head necrosis, treatment for retaining the femoral head should be performed as early as possible. German guidelines suggest early but not emergency treatment in case of operations not saving the femoral head. Emergency operation within 6 h is not mandatory.


Quantitative planar thallium-201 stress scintigraphy: a critical evaluation of the method.
The results of quantitative analysis of planar thallium-201 stress scintigraphy are superior to those of visual analysis. The increased sensitivity for detection of coronary artery disease is associated with maintenance of specificity. Consequently, we believe that quantitative analysis is the state-of-the-art for planar 201Tl stress scintigraphy. We emphasize that for reliable and reproducible results, rigorous quality control and strict adherence to a standardized imaging protocol are necessary. An important feature is clarity of display of computer data. In our experience, the most important feature for making quantitative analysis reliable and accessible for a broader user market is simultaneous display of the lower limits of normal with processed patient data. This provides a simple visual impression of the degree and extent of abnormal 201Tl distribution and kinetics relative to the lower limit of normal.


Assessing the Performance of a Real-Time Total Adenylate (ATP+ADP+AMP) Detection Assay for Surface Hygiene Monitoring in Food Manufacturing Plants and Commercial Kitchens.
Environmental hygiene monitoring in the food processing environment has become important in current food safety programs to ensure safe food production. However, conventional monitoring of surface hygiene based on visual inspection and microbial counts is slow, tedious, and thus unable to support the current risk-based management system. Therefore, this study was conducted to assess the performance of a real-time total adenylate assay that detected ATP+ADP+AMP (A3) for food contact surface hygiene in 13 food processing plants and two commercial kitchens in Malaysia. The A3 value was compared with the microbial count (aerobic plate count [APC]) on food contact surfaces. Receiver-operating characteristic (ROC) analysis was performed to assess the reliability of the data and to determine the optimal threshold value for hygiene indication of food contact surfaces. Overall, the A3 value demonstrated a weak positive relationship with APC. However, the A3 value significantly correlated with APC for food processing environments associated with raw meat and raw food ingredients such as fruit that harbor a high microbial load. ROC analysis suggested an optimal threshold for the A3 value of 500 relative light units to balance the sensitivity and specificity at 0.728 and 0.719, respectively. The A3 assay as a hygiene indicator for food contact surfaces had an efficiency of 72.1%, indicating its reliability as a general hygiene indicator.


Predictive value of XPD polymorphisms on platinum-based chemotherapy in non-small cell lung cancer: a systematic review and meta-analysis.
The correlation between xeroderma pigmentosum group D (XPD) polymorphisms (Lys751Gln and Asp312Asn) and clinical outcomes of non-small cell lung cancer (NSCLC) patients, who received platinum-based chemotherapy (Pt-chemotherapy), is still inconclusive. This meta-analysis was aimed to systematically review published evidence and ascertain the exact role of XPD polymorphisms. Databases of MEDLINE and EMBASE were searched up to April 2013 to identify eligible studies. A rigorous quality assessment of eligible studies was conducted according the Newcastle-Ottawa Quality Assessment Scales. The relationship between XPD polymorphisms and response to Pt-chemotherapy and survival was analyzed. A total of 22 eligible studies were included and analyzed in this meta-analysis. The overall analysis suggested that the XPD Lys751Gln polymorphism was not associated with response to Pt-chemotherapy or survival. However, the XPD 312Asn allele was significantly associated with poor response to Pt-chemotherapy compared with the Asp312 allele (Asn vs. Asp: OR = 0.435, 95% CI: 0.261-0.726). Additionally, the variant genotype of XPD Asp312Asn polymorphism was associated with favorable survival in Caucasian (AspAsn vs. AspAsp: HR = 0.781, 95% CI: 0.619-0.986) but unfavorable survival in Asian (AspAsn+AsnAsn vs. AspAsp: HR = 1.550, 95% CI: 1.038-2.315). These results suggest that XPD Asp312Asn polymorphism may function as a predictive biomarker on platinum-based chemotherapy in NSCLC and further studies are warranted.


Semaphorin 4D induced inhibitory synaptogenesis decreases epileptiform activity and alters progression to Status Epilepticus in mice.
Previously we demonstrated that intra-hippocampal infusion of purified, Semaphorin 4D (Sema4D) extracellular domain (ECD) into the mouse hippocampus rapidly promotes formation of GABAergic synapses and decreases seizure susceptibility in mice. Given the relatively fast action of Sema4D treatment revealed by these studies, we sought to determine the time course of Sema4D treatment on hippocampal network activity using an acute hippocampal slice preparation. We performed long-term extracellular recordings from area CA1 encompassing a 2-hour application of Sema4D and found that hippocampal excitation is suppressed for hours following treatment. We also asked if Sema4D treatment could ameliorate seizures in an acute seizure model: the kainic acid (KA) mouse model. We demonstrate that Sema4D treatment delays and suppresses ictal activity, delays the transition to Status Epilepticus (SE), and lessens the severity of SE. Lastly, we sought to explore alternative methods of Sema4D delivery to hippocampus and thus created an Adeno Associated Virus expressing the ECD of Sema4D. Our data reveal that virally delivered, chronically overexpressed Sema4D-ECD promotes GABAergic synapse formation and suppresses ictal activity and progression to SE. These results provide proof of concept that viral delivery of Sema4D is an efficacious and promising delivery method to abate epileptiform activity and progression to SE.


On the mapping of chains of first order chemical reactions on random walks.
We present the transient solution to a random walk problem which characterizes chemical kinetic processes in which a particular state may have a finite number of internal states. While there are many chemical and physical examples, we introduce the solution through models of biophysical interest.


A new high resolution radioimager for the quantitative analysis of radiolabelled molecules in tissue section.
We present a high-speed, high-resolution imager of beta particles. It is devoted to be used in autoradiography experiments such as receptor binding or in situ hybridization experiments, either instead of, or in complement with autoradiographic film and emulsions. It allows the user to locate and perform quantitative analyses of (3H, 14C, 35S, 33P, 32P, 125I) labelled molecules with a 15 microm spatial resolution on a 0.9 x 1.3 cm2 sensitive area. Combining recent techniques (specific scintillator thin sheets and intensified charge-coupled device (CCD)) this imager offers a wide dynamic range and real-time acquisition.


A waterborne tularemia outbreak.
A waterborne tularemia outbreak is described. Forty nine cases were identified in Sansepolcro, a small Medioeval town in the province of Arezzo, Tuscany, Italy. All cases had laterocervical or sub-mandibular adenitis, and occurred within a period of three weeks during March and April 1982. The study showed association between cases and the consumption of water from an unchlorinated water system. Francisella tularensis type 1 was isolated from wild hares captured in the area.


Separation of Nuclear and Cytoplasmic Fractions for Chimeric RNA Characterization.
Cellular organelle fractionation, a basic technique in molecular biology, has been devised to separate various cell components, which can then be purified and analyzed biochemically. Isolation of proteins or RNAs from these fractions provides insight into fraction-specific or even organelle-specific expression, which may indicate potential modes of functionality or likelihood for a transcript to encode a protein. These findings can be further utilized to observe differences in expression between normal and diseased cell states, such as cancer. We utilize these techniques to observe expression of chimeric RNAs in these fractions. Within this chapter we describe the most frequently used cellular fractionation technique: the separation of the cytoplasmic fraction from the nuclear fraction in a cell.


A comparison of threshold and suprathreshold appearance of gratings with components in the low and high spatial frequency range.
1. The appearance of square gratings with some of their Fourier components missing has been investigated for both threshold and suprathreshold contrasts.2. If high frequency components are removed from a square grating there is only a very small effect on the detection threshold, or suprathreshold appearance, unless the components are visible by themselves.3. If the fundamental frequency is removed from a square-wave grating which has a spatial frequency lower than 1 cycle per degree (c/d) the contrast sensitivity is not altered. This is a generalisation of the Craik-Cornsweet illusion. If the contrast is raised above the detection threshold the grating is indistinguishable from a square grating, unless the contrast is high enough to see the fundamental when it is presented alone.4. If the fundamental is removed from a square grating which has a spatial frequency higher than 1 c/d the contrast threshold and the appearance at all contrasts are changed. At threshold it appears as a sinusoidal grating of three times the fundamental frequency. The threshold is dictated solely by the amplitude of the third harmonic. If the contrast is further raised, so that the fifth harmonic also reaches threshold, the periodictiy of the fundamental is seen.5. Therefore, gratings of many different luminance profiles (including the Craik-Cornsweet profile) all produce the perception of a square grating simply because those missing components which would be required in each case to produce a perfect square are by themselves undetectable. The visual system responds as though hardwired to detect square gratings and edges by means of quasi-Fourier analysis.6. These results are analagous to the missing fundamental, or residue, effect in hearing.


Ordered Heterostructured Aerogel with Broadband Electromagnetic Wave Absorption Based on Mesoscopic Magnetic Superposition Enhancement.
Demand for lightweight and efficient electromagnetic wave (EW) absorbers continues to increase with technological advances in highly integrated electronics and military applications. Although MXene-based EW absorbers have been extensively developed, more efficient electromagnetic coupling and thinner thickness are still essential. Recently, ordered heterogeneous materials have emerged as a novel design concept to address the bottleneck faced by current material development. Herein, an ordered heterostructured engineering to assemble Ti3 CNTx MXenes/Aramid nanofibers/FeCo@SiO2 nanobundles (FS) aerogel (AMFS-O) is proposed, where the commonly disordered magnetic composition is transformed to ordered FS arrays that provide more powerful magnetic loss capacity. Experiments and simulations reveal that the anisotropy magnetic networks enhance the response to the magnetic field vector of EW, which effectively improves the impedance matching and makes the reflection loss (RL) peaks shift to lower frequencies, leading to the thinner matching thickness. Furthermore, the temperature stability and excellent compressibility of AMFS-O expand functionalized applications. The synthesized AMFS-O achieves full-wave absorption in X and Ku-band (8.2-18.0 GHz) at 3.0 mm with a RLmin of -41 dB and a low density of 0.008 g cm-3 . These results suggest that ordered heterostructured engineering is an effective strategy for designing high-performance multifunctional EW absorbers.


Feasibility of vertical force-velocity profiles to monitor changes in muscle function following different fatigue protocols.
This study aimed to explore the feasibility of vertical force-velocity (F-V) profiles to monitor changes in muscle function following different fatigue protocols. The between-day reliability of vertical F-V profiles and the acute effects of two fatigue protocols on the changes of lower limb muscle function were examined. Twelve resistance trained males completed a preliminary session to determine their back squat one-repetition maximum (1RM). Afterwards, they randomly performed two experimental sessions that only differed in the fatigue protocol applied: heavy-load traditional (HLT; five repetitions at 80% 1RM) and light-load ballistic (LLB; five repetitions at 30% 1RM) squat protocols. Participants' vertical F-V profiles (maximum theoretical force [F0], maximum theoretical velocity [v0], and maximum power output [Pmax]) were calculated before and immediately after each fatigue protocol. F0, v0, and Pmax showed acceptable to good between-day reliability (coefficient of variation ≤ 4.4%; intraclass correlation coefficient ≥ 0.84). Both fatigue protocols promoted a comparable reduction in Pmax (-10.1% for HLT and -12.2% for LLB). However, the LLB squat protocol reduced more v0 (-9.7%) than F0 (-0.4%), while the HLT squat protocol reduced F0 (-8.4%) more than v0 (-4.1%). The vertical F-V profile can be used to monitor changes in muscle function given its acceptable between-day reliability and its high sensitivity to detect the acute effect of force-oriented and velocity-oriented fatigue protocols on specific maximal neuromuscular capacities.


Quality of life of critical care nurses and impact on anxiety, depression, stress, burnout and sleep quality: A cross-sectional study.
To investigate how anxiety, depression, stress, burnout, and sleep quality impact on Quality of life of critical care nurses. Several studies reported that critical care nurses are exposed to a high risk of anxiety, depression, burnout, stress, and sleep quality, but we do not know the impact of critical care nurses. A cross-sectional study. We have included all critical care nurses working in the intensive care unit for at least six months. Data were collected from December 1, 2021, to March 18, 2022. We evaluated the critical care nurses using the Depression Anxiety Stress Scale (DASS), Maslach Burnout Inventory scale, Pittsburgh Sleep Quality Index and Nurse Quality of Life. The primary endpoint is Quality of Life. Associations were tested using multivariate modelling. A total of 140 critical care nurses were included. Multivariate regression showed the relation between emotional QoL and emotional exhaustion and DASS total score [OR = 0.14; 95% CI (0.03-0.73); p = 0.019 and OR = 3.64; 95% CI (1.07-12.32); p = 0.038, respectively]. Personal accomplishment and DASS total score have a direct relationship on quality of work-life [OR = 0.21; 95% CI (0.05-0.82); p = 0.024 and OR = 4.18; 95% CI (1.01-17.33); p = 0.049, respectively]. The physical quality of life is not optimal in critical care nurses, while burnout and the DASS score directly impact the emotional and work-life quality of life. Our research has highlighted the importance of detecting the quality of life of critical care nurses. The nurses should take proper care of their health by adopting the right health behaviours to create correct work conditions and increase the quality of care for critically ill patients.


Negative regulation of human c-fos expression by the retinoblastoma gene product.
Inactivation of the retinoblastoma susceptibility gene (RB-1) has been associated with the aetiology of many types of human cancers, leading to the classification of RB-1 as an anti-oncogene or tumour suppressor gene. Given that the protein product of RB-1 (Rb) has a nuclear localization and DNA-binding activity in vitro, it is possible that Rb regulates transcription of certain genes. The promoter of the c-fos gene might be a target for regulation by Rb, because both v-fos and RB-1 are associated with the induction of osteosarcomas in mice and humans, respectively. Also, fos expression is thought to be required for quiescent cells to enter the cell cycle, making the fos promoter an attractive target for suppressors of cell growth. Here we report that Rb can repress c-fos expression and AP-1 transcriptional activity in both serum-induced and cycling 3T3 cells. We have mapped a cis-acting element in the human c-fos promoter that can confer repression by Rb to a heterologous promoter. We have the termed the cis-acting sequence regulated by Rb the retinoblastoma control element.


Improved distribution analysis of cobalamins and cobalamin analogues in human plasma in which the use of thiol-blocking agents is a prerequisite.
In this paper the quantitative analysis of cobalamins and cobalamin analogues in human plasma by means of high performance liquid chromatography (HPLC) and radioisotope dilution assay (RIDA) is described. Current methods for the extraction of cobalamins from plasma proved impracticable due to the selective loss of hydroxo- and sulphitocobalamin, caused by concomitant reduction to the Co2+ form and tight binding to thiol groups of denatured plasma proteins. Although this process can be prevented by exchange of the hydroxyl group with sulphite, azide or nitrite ions, further separation of the respective cobalamin forms from the other endogenous cobalamins by HPLC proved to be impossible. Efficient extraction of hydroxo- and sulphitocobalamin has been obtained in the presence of the thiol-blocking agent N-ethylmaleimide, which does not interfere with the subsequent chromatographic separation of any of the plasma cobalamin forms. The use of R-binder free Intrinsic Factor and salivary R-binder separately as binding substances in RIDA made it possible to analyse the distribution of biologically active cobalamins as well as cobalamin analogues over the various HPLC fractions. Analyses are reported of 15 normal human plasma samples, in which the major components were found to be methylcobalamin (46.9 +/- 4.5%, mean +/- SD) and hydroxocobalamin (40.4 +/- 7.1%, mean +/- SD). Analyses of plasma extracts in the absence of N-ethylmaleimide showed a gross relative overestimation of the amount of methylcobalamin, due to loss of hydroxocobalamin during the extraction procedure. Cobalamin analogues appeared to be evenly distributed over the cobalamin fractions in a pattern almost similar to that of the biologically active forms.


Evaluation of physical-chemical properties and biocompatibility of a microrough and smooth bioactive glass particles.
The purpose of this study was to evaluate physical-chemical and biocompatibility characteristics of a simple synthesis and low cost experimental bioactive glass. Physical and chemical properties were analyzed using scanning electron microscopy (SEM), X-ray energy dispersive (EDX), X-ray fluorescence (XRF) and X-ray diffraction (XRD). The biomaterials were subcutaneously implanted into rats, according to the following groups: G1, PerioGlastrade mark; G2, Biograntrade mark, G3, Experimental Bioactive Glass U (BGU) and G4, Control (Sham). After 7, 15, 21, 45, and 60 days, 5 animals/group/period were sacrificed and the subcutaneous tissue was dissected for histological and histometric analysis, considering inflammatory reaction and granulation area, presence of polymorphonuclear (PMN), monuclear (MN) and fibroblast (F) cells. SEM analysis of biomaterials showed irregular particles with different surface characteristics. EDX showed calcium, oxygen, sodium, phosphorus and silicon; XRF revealed silica oxide (SiO(2)), sodium oxide (Na(2)O), calcium oxide (CaO) and phosphorus oxide (P(2)O(5)). XRD indicated non crystalline phase. Measurement of tissue reaction showed similar results among the experimental groups at 45 and 60 days. No difference was found for PMN, MN and F cell counts. All biomaterials exhibited partial resorption. In conclusion, the experimental bioactive glass analyzed showed physical and chemical characteristics similar to the commercially available biomaterials, and was considered biocompatible, being partially reabsorbed in the subcutaneous tissue.


Cardiac functions in children with growth hormone deficiency: Effects of one year of GH replacement therapy.
Children with Growth Hormone deficiency (GHD) are prone to heart dysfunction and, if left untreated, will result in marked cardiac dysfunction in adulthood. The aim was to evaluate the effect of GHD and growth hormone (GH) therapy on cardiac structure in children and adolescents, and to investigate the role of insulin like growth factor-1 (IGF-1) in this. M-mode, pulse-wave Doppler echocardiography and tissue Doppler imaging (TDI) were performed in 49 children with GHD who were divided into those with a peak GH response < 7 μg/L and 7-10 μg/L after two GH stimulation tests, aged 8-16 years at baseline and at six and 12 months after GH initiation, and 49 healthy peers. IGF-1 concentration was measured. Although the left ventricular end diastolic and systolic diameters in both GH deficient groups were significantly lower than controls (p < 0.01), both diameters increased significantly with one year of treatment and achieved normal values (p > 0.05). Using TDI in both two patients group revealed increased E/A, prolonged isovolumic relaxation time, shortened ejection time, and a significant increase in myocardial performance index compared to controls (p < 0.001). Significant improvement was observed in these parameters from the sixth month of GH treatment (p < 0.001), this improvement does not match parameters measured in healthy peers, even after one year of treatment in both patients group. (p < 0.001). No correlation was found between IGF-1 concentration and any echocardiographic parameter. Echocardiographic parameters were similar in children with a GH peak < 7 μg/L and 7-10 μg/L. In TDI, both systolic and diastolic function was impaired in GHD children compared to controls. These parameters improved after one year of GH therapy but did not recover to healthy control levels.


Intracranial oculomotor nerve paresis with anisocoria and pupillary parasympathetic hypersensitivity.
Three patients developed anisocoria as a result of third nerve palsies caused by intracranial lesions: two in the cavernous sinus and one in the mesencephalon. Pharmacologic testing using low concentration pilocarpine showed apparent preganglionic parasympathetic supersensitivity of the abnormal pupil. These findings are compatible with the existence of a proposed direct pathway from the midbrain to the eye, without synapse at the ciliary ganglion. Cholinergic hypersensitivity can occur, not only with postciliary ganglionic but also with preciliary ganglionic parasympathetic lesions.


Comparative in vitro activity of the new quinolone sparfloxacin (CI-978, AT-4140) against nosocomial gram-negative bloodstream isolates.
The in vitro activity of sparfloxacin (CI-978, AT-4140), a new quinolone which is active against gram-negative and gram-positive bacteria, and nine other broad-spectrum antibiotics was tested against 128 gram-negative nosocomial bloodstream isolates from separate patients. Sparfloxacin and ciprofloxacin were among the most potent antibiotics against Escherichia coli (n = 40), Enterobacter cloacae (n = 18), Klebsiella oxytoca (n = 13), and Klebsiella pneumoniae (n = 19), with MIC90 values of less than or equal to 0.25 microgram/ml. Ciprofloxacin was slightly more potent than sparfloxacin against Serratia marcescens (n = 14), the MIC90 values being 0.25 and 1.0 micrograms/ml respectively, although all strains were susceptible to both agents. Sparfloxacin was slightly less potent than ciprofloxacin against Pseudomonas aeruginosa (n = 24), the MIC90 values being 4.0 and 0.5 micrograms/ml respectively. Overall, the in vitro activity of sparfloxacin compared favorably with that of ciprofloxacin and the other broad spectrum agents tested against nosocomial gram-negative bloodstream isolates.


Role of ischemia-modified albumin and total homocysteine in estimating symptomatic lacunar infarction in type 2 diabetic patients.
To investigate whether ischemia-modified albumin (IMA) is reliable for early diagnosing symptomatic lacunar infarction (SLI) in type 2 diabetics. Ninety-seven consecutive diabetic patients, 47 with SLI, and 45 healthy controls were enrolled. Serum IMA and plasma total homocysteine (tHcy) were measured on an autoanalyzer and evaluated in distinguishing SLI. Serum IMA levels were 97.35 ± 5.25 U/L in the healthy control group, 103.26 ± 7.43 U/L in the non-SLI group, and 139.84 ± 20.00 U/L in the SLI group. Plasma tHcy levels were 8.08 ± 1.82 μmol/L, 11.31 ± 3.03 μmol/L, and 13.10 ± 3.67 μmol/L, respectively. The differences in IMA and tHcy levels were statistically significant for all groups (p<0.05). Receiver operating characteristic curve analyses revealed the areas under curve were 0.866 for IMA and 0.352 for tHcy. This study indicates that IMA was significantly elevated in the acute phase of SLI and more sensitive than tHcy in distinguishing SLI.


Nonpolar interactions in the modification of an essential sulfhydryl of sorbitol dehydrogenase by N-alkylmaleimides.
A series of N-alkylmaleimides varying in chainlength from N-methyl- to N-octylmaleimide inclusive was shown to effectively inactivate sheep liver sorbitol dehydrogenase at pH 7.5 and 25 degrees C. The apparent second-order rate constants for inactivation increased with increasing chainlength of the N-alkylmaleimide used. Positive chainlength effects were also indicated by the Kd values for the N-ethyl and N-heptyl derivatives obtained from studies of the saturation kinetics observed for inactivation of the enzyme at high concentrations of these maleimides. The complete inactivation of sorbitol dehydrogenase was demonstrated to occur through the selective covalent modification of one cysteine residue per subunit of enzyme. The stoichiometry of enzyme inactivation was supported on the one hand by fluorescence titration with fluorescein mercuric acetate of the native and the inactivated enzyme, and, on the other hand, by the simultaneous inactivation of the enzyme with selective modification of one sulfhydryl per subunit by N-[p-(2-benzoxazolyl)phenyl]maleimide. Protection of the enzyme from N-alkylmaleimide inactivation was observed with the binding of NADH, whereas both NAD and sorbitol were ineffective as protecting ligands. Diazotized 3-aminopyridine adenine dinucleotide, in contrast to previous studies of this reagent with yeast alcohol dehydrogenase and rabbit muscle glycerophosphate dehydrogenase, did not function as a site-labeling reagent for sorbitol dehydrogenase.


Income Generation Programs for Persons with Mental Health Challenges: Practices from 13 Indian Mental Health Rehabilitation Centers.
In India, mental health rehabilitation centers run income generation programs (IGP) for therapeutic engagement, skills training, and income generation of clients. The centers have evolved IGP models relevant to their settings. There is a paucity of published literature on practices employed by the centers. This paper compiles data gathered from visits to 13 centers between November 2018 and April 2019. Information was collected through observation and interviews with staff involved in IGP, using a semi-structured pro forma designed for study. Most centers were based in south India (n = 11) and urban areas (n = 12). Each center ran two to seven IGP. Each center involved 20-50 clients in IGP. Clients involved in IGP were aged 20-60 years. The centers ran a range of IGP, including the manufacturing of household consumables, paper products, textile products, handicraft products, food products, and jute products; animal husbandry and horticulture initiatives; and running cafeterias and petty shops. IGP were mostly selected based on market demand and sales value of products (n = 11); ease of doing (n = 5); interests, abilities, exposure, and experience of clients (n = 5); and availability of resources (n = 3). Products were priced primarily to cover input and labor costs (n = 8), and many centers sold products below the market rates (n = 5). Running stalls during public events was a common strategy for the sale of products (n = 9). Personal contacts and "word of mouth" publicity were used for advertisement (n = 6). Four centers involved family members in IGP. The nature of IGP varied in terms of setting, available resources, and profile of clients availing the services. Marketing and sales were a challenge. A supportive framework of policies and schemes is essential to promote IGP at mental health rehabilitation centers. This report may be helpful for professionals and centers planning to set up an IGP.


Kaposi sarcoma-associated herpesvirus latency-associated nuclear antigen: more than a key mediator of viral persistence.
Kaposi sarcoma-associated herpesvirus (KSHV), or human herpesvirus-8, is an oncogenic herpesvirus. Its latency-associated nuclear antigen (LANA) is essential for the persistence of KSHV in latently infected cells. LANA mediates replication of the latent viral genome during the S phase of a dividing cell and partitions episomes to daughter cells by attaching them to mitotic chromosomes. It also mediates the establishment of latency in newly infected cells through epigenetic mechanisms and suppresses the activation of the productive replication cycle. Furthermore, LANA promotes the proliferation of infected cell by acting as a transcriptional regulator and by modulating the cellular proteome through the recruitment of several cellular ubiquitin ligases. Finally, LANA interferes with the innate and adaptive immune system to facilitate the immune escape of infected cells.


Anti-idiotypes against anti-H-2 antibodies VI. Detection of shared idiotypes among monoclonal anti-H-2 antibodies.
Anti-idiotypes produced against monoclonal anti-H-2 antibodies have been used to examine idiotope sharing among a panel of anti-major histocompatibility complex (MHC) antibodies detecting the same and different specificities. Both xenogeneic anti-100-30 and anti-3-83, which did not react with predominant idiotypes in conventional alloantisera, detected idiotopes on 3-83 and 100-30 as well as on 2 other monoclonal anti-H-2Kk antibodies. All 4 monoclonal antibodies recognized the same epitope cluster on the Kk molecule and detected the same serological specificity. H-2.5. In contrast, syngeneic and allogeneic anti-idiotype produced against the same monoclonal antibodies did not detect these cross-reactive determinants. In several instances, xenogeneic anti-idiotype reacted with anti-MHC antibodies which recognized distinct H-2 determinants, suggesting that anti-MHC antibodies detecting the same or different specificities may share idiotypic determinants. These reagents may be useful probes of the anti-MHC immune repertoire.


Lymph drainage and cervical fascia anatomy-oriented differential nodal CTV delineation at the supraclavicular region for esophageal cancer and nasopharyngeal cancer.
To determine the differences in supraclavicular lymph node metastasis between esophageal cancer (EC) and nasopharyngeal cancer (NPC) and explore the feasibility of differential supraclavicular clinical target volume (CTV) contouring between these two diseases based on the involvement of different fascial spaces. One hundred patients with supraclavicular nodes positive for EC or NPC were enrolled, and their pre-treatment images were reviewed. The distribution patterns of nodes between the two diseases were compared in the context of node levels defined by the 2017 Japanese Esophageal Society and 2013 International Consensus on Cervical Lymph Node Level Classification. Grouping supraclavicular nodes based on sub-compartments formed by the cervical fascia was discussed, and the feasibility of differential CTV contouring based on the differences in the involvement of these sub-compartments between EC and NPC was explored. The 2013 Consensus on cervical node levels and 2017 Japanese Esophageal Society node station could not practically guide supraclavicular CTV contouring. We divided the supraclavicular space into six sub-compartments: the para-esophageal space (PES), carotid sheath space (CSS), sub-thyroid pre-trachea space (STPTS), pre-vascular space (PVS), and vascular lateral space (VLS) I and II. EC mainly spread to the PES, STPTS, CSS, and VLS I, whereas NPC tended to spread to the CSS, VLS I, and VLS II. These combinations of sub-compartments may help constitute the supraclavicular CTVs for EC and NPC. The fascia anatomy-based sub-compartments sufficiently distinguished metastasis to the supraclavicular space between EC and NPC, thus facilitating differential CTV contouring between these two diseases.


(L)-(Trimethylsilyl)alanine synthesis exploiting hydroxypinanone-induced diastereoselective alkylation.
A new and efficient synthesis of (L)-(trimethylsilyl)alanine (TMSAla) with suitable protection for use in Solid Phase Peptide Synthesis (SPPS) has been accomplished starting from glycine tert-butyl ester and using hydroxypinanone as chiral inductor. The silylated side chain was introduced by alkylation of the Schiff base intermediate with iodomethyl(trimethylsilane) at -78 °C. Among the different synthetic routes that were tested including several chiral inductors and different Schiff bases, this strategy was selected and afforded (L)-TMSAla in good chemical overall yield with 98 % ee.


[Transgenic mice model of human hepatitis B virus x gene].
To set up a human hepatitis B virus x (HBx) gene transgenic model. The model was set up by microinjection, the integration and expression of the founders were identified by molecular hybridization. A 1,800 bp DNA fragment containing the human HBx promoter and genomic DNA was microinjected into the male pronucleus of the fertilized eggs of mice. Three hundred and thirty-eight eggs survived from microinjection were transplanted into the oviduct of 16 pseudopregnant female, 12 pseudopregnant mice got pregnant and gave birth to 74 pups. Genomic DNA were extracted from the tails of the pups, Southern blot hybridization was used for determination of the integration of human HBx gene. The 1,800 bp microinjected fragment was used as the probe, 17 mice (founders) were identified of the integration of human HBx gene. Total RNA were extracted from the livers of the founders, all 17 founders were identified of the expression of human HBx gene by using Northern blot hybridization. These results may provide animal models for studying on the correlation between chronic HBV infection and the development of hepatocellular carcinoma.


Distributed synthesis of sarcolemmal and sarcoplasmic reticulum membrane proteins in cardiac myocytes.
It is widely assumed that synthesis of membrane proteins, particularly in the heart, follows the classical secretory pathway with mRNA translation occurring in perinuclear regions followed by protein trafficking to sites of deployment. However, this view is based on studies conducted in less-specialized cells, and has not been experimentally addressed in cardiac myocytes. Therefore, we undertook direct experimental investigation of protein synthesis in cardiac tissue and isolated myocytes using single-molecule visualization techniques and a novel proximity-ligated in situ hybridization approach for visualizing ribosome-associated mRNA molecules for a specific protein species, indicative of translation sites. We identify here, for the first time, that the molecular machinery for membrane protein synthesis occurs throughout the cardiac myocyte, and enables distributed synthesis of membrane proteins within sub-cellular niches where the synthesized protein functions using local mRNA pools trafficked, in part, by microtubules. We also observed cell-wide distribution of membrane protein mRNA in myocardial tissue from both non-failing and hypertrophied (failing) human hearts, demonstrating an evolutionarily conserved distributed mechanism from mouse to human. Our results identify previously unanticipated aspects of local control of cardiac myocyte biology and highlight local protein synthesis in cardiac myocytes as an important potential determinant of the heart's biology in health and disease.


Amino-functionalized hierarchical porous SiO2-AlOOH composite nanosheets with enhanced adsorption performance.
Hierarchical porous SiO2-AlOOH composite nanosheets (HPSA) with a three-dimensional (3D) structure were prepared from two-dimensional (2D) layered mineral kaolinite (A12Si2O5(OH)4) via a template-free structural reorganization method. The obtained material was subjected to homogeneous and effective amino-functionalization by grafting it with (3-aminopropyl) triethoxysilane. Owing to the enhanced 3D hierarchical meso-macroporous structure containing highly dispersed protonated amino groups (NH3+), the as-prepared amino-functionalized HPSA (NH2-HPSA) showed unique adsorption performance towards the congo red anionic dye. It provides feasibilities to fabricate other functional hierarchical porous materials from clay minerals, which can offer potential applications in adsorption, separation, catalysis and other environmental remediation fields.


Acute kidney injury in advanced lung cancer patients treated with PD-1 inhibitors: a single center observational study.
Immune checkpoint inhibitor (ICI) therapy is now the stand of care for lung cancer. Due to the low incidence, the study of acute kidney injury (AKI) in lung cancer patients treated with ICIs was hardly reported. We focused on the incidence, characteristics, risk factors, and mortality of AKI in advanced lung cancer patients receiving PD-1 inhibitors. We reviewed advanced lung cancer patients receiving PD-1 inhibitors between January 2018 to August 2020 at Jiangsu Province Hospital. Patients were followed up for 6 months. We used the logistic regression model to evaluate risk factors for AKI, and Kaplan-Meier method to assess the association between AKI and mortality. A total of 305 advanced lung cancer patients treated with PD-1 inhibitors. The median age was 64 years and 80.6% of patients were male. The incidence of AKI was 10.2%, and the incidence of ICI-AKI was 4.6%. Multivariate analysis showed that concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) (OR 2.509; 95% CI 1.053-5.974) and renin-angiotensin-aldosterone system (RAAS) inhibitors (OR 2.656; 95% CI 1.091-6.466) were risk factors for AKI. In addition, concomitant use of NSAIDs (OR 5.170; 95% CI 1.087-24.595) and RAAS inhibitors (OR 5.921; 95% CI 1.871-18.737), and the occurrence of extra-renal immune-related adverse events (OR 4.726; 95% CI 1.462-15.280) were significantly associated with ICI-AKI. ICI-AKI was not associated with mortality while severe AKI was associated with higher risk of mortality. AKI is common in advanced lung cancer patients treated with PD-1 inhibitors. The characteristics and risk factors of ICI-AKI were similar to those previously reported in other solid organ malignancies treated with ICIs. Severe AKI may indicate higher mortality.


Role of L1CAM for axon sprouting and branching.
The central nervous system (CNS) has been traditionally considered as an organ that fails to regenerate in response to injury. Indeed, the lesioned CNS faces a number of obstacles during regeneration, including an overall non-permissive environment for axonal regeneration. However, research during the last few decades has identified axon sprouting as an anatomical correlate for the regenerative capability of the CNS to establish new connections. The immunoglobulin superfamily member L1CAM has been shown to promote the capability of neurons for regenerative axon sprouting and to improve behavioral outcomes after CNS injury. Here, we discuss the cell-autonomous role of L1CAM for axon sprouting in experimental rodent injury models and highlight the molecular interactions of L1CAM with ankyrins, ezrin-radixin-moesin proteins and the Sema3A/Neuropilin ligand-receptor complex in the context of axonal branching.


Surgical anatomy of the atrioventricular conduction bundle in tetralogy of Fallot. New findings relevant to the position of the sutures.
To avoid three of the causes of right ventricular end-diastolic pressure elevation, complete heart block, residual leakage, and fixing of tricuspid septal leaflet, we studied detailed anatomy of the posteroinferior corner of the ventricular septal defect of tetralogy of Fallot in 81 specimens. A new stitching method was applied in 79 patients with tetralogy of Fallot. Sixty-eight specimens (84%) had perimembranous outlet ventricular septal defect with a membranous flap 4.5 +/- 2.6 mm long. Thirteen (16%) had a muscle bar separating the defect from the central fibrous body area. The width was 5.8 +/- 1.7 mm. Microscopic study revealed that the membranous flap is a safe structure for suturing because of the thick posterior extension of the trabecular septomarginalis. In the clinical application of a new stitching method that uses the membranous flap, all patients showed sinus rhythm and no patient had complete heart block. We conclude that a membranous flap can be used safely as a suture line to avoid conduction tissue damage without using the tricuspid septal leaflet.


Effect of streptozotocin-induced diabetes on the metabolism of ADP, AMP and adenosine in the pulmonary circulation of rat isolated lung.
The uptake and metabolism of radioactive ADP, AMP and adenosine was investigated in the pulmonary circulation of lungs taken from rats with streptozotocin-induced diabetes. Between 0.26 and 500 mumol/l ADP was extensively hydrolysed to AMP equally in control and diabetic lungs. At 1 mmol/l there was less ADP breakdown in diabetic lungs. Hydrolysis of AMP to adenosine was also less in diabetic lungs at 10 mumol/l and 1 mmol/l substrate concentration, but adenosine metabolism and uptake at these concentrations was not affected by diabetes. The results indicate that formation of the anti-aggregatory adenosine and, to a lesser extent, breakdown of the pro-aggregatory ADP were decreased in diabetic lungs and may contribute to the platelet hyperreactivity associated with diabetes.


Effect of staurosporine-induced apoptosis on endothelial nitric oxide synthase in transfected COS-7 cells and primary endothelial cells.
Nitric oxide (NO) may block apoptosis by inhibiting caspases via S-nitrosylation of cysteines. Here, we investigated whether effector caspases might cleave and thereby inhibit endothelial nitric oxide synthase (eNOS). Exposure of eNOS-transfected COS-7 cells and bovine aortic endothelial cells to staurosporine resulted in significant loss of 135-kDa eNOS protein and activity, and appearance of a 60-kDa eNOS fragment; effects were inhibited by the general caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp[OMe]-fluoromethyl ketone (zVAD-fmk). In eNOS-transfected COS-7 cells, staurosporine-induced activation of caspase-3 and poly(ADP-ribose) polymerase (PARP) cleavage coincided with increased eNOS degradation and decreased activity. Loss of eNOS activity was greater than the degree of proteolysis. Incubation of immunoprecipitated eNOS with caspase-3, caspase-6 or caspase-7 resulted in eNOS cleavage. Staurosporine, a general protein kinase inhibitor, also reduced phosphorylation and decreased calmodulin binding, an effect that may explain the reduction in activity. eNOS, therefore, is both an inhibitor of apoptosis and a target of apoptosis-associated proteolysis.


Incidence of cleft lip and palate in Sri Lanka.
In a prospective study that surveyed 51,542 live births and 5,263 still births in central Sri Lanka, cleft lip with or without cleft palate (CL +/- P) was found to have an incidence of 0.83 per 1,000 births, and isolated cleft palate (CP) an incidence of 0.19 per 1,000 births. Distribution by sex, type of cleft, and site was similar to that in whites. Family history was positive in 19.6% of CL +/- P and in 9.1% of CP subjects. Furthermore, the frequency of CL +/- P in relatives of subjects with CL +/- P was significantly greater than that of CP. Of the three major ethnic groups that inhabit Sri Lanka, the incidence was significantly greater in the Moors than in the Sinhalese and the Tamils. Social status was found to have no association with the occurrence of clefts.


Meta-analysis on shift work and risks of specific obesity types.
This systematic review and meta-analysis evaluated the associations between shift work patterns and risks of specific types of obesity. PubMed was searched until March 2017 for observational studies that examined the relationships between shift work patterns and obesity. Odds ratio for obesity was extracted using a fixed-effects or random-effects model. Subgroup meta-analyses were carried out for study design, specific obesity types and characteristics of shift work pattern. A total of 28 studies were included in this meta-analysis. The overall odds ratio of night shift work was 1.23 (95% confidence interval = 1.17-1.29) for risk of obesity/overweight. Cross-sectional studies showed a higher risk of 1.26 than those with the cohort design (risk ratio = 1.10). Shift workers had a higher frequency of developing abdominal obesity (odds ratio = 1.35) than other obesity types. Permanent night workers demonstrated a 29% higher risk than rotating shift workers (odds ratio 1.43 vs. 1.14). This meta-analysis confirmed the risks of night shift work for the development of overweight and obesity with a potential gradient association suggested, especially for abdominal obesity. Modification of working schedules is recommended, particularly for prolonged permanent night work. More accurate and detailed measurements on shift work patterns should be conducted in future research.


Removal of humic acid using TiO2 photocatalytic process--fractionation and molecular weight characterisation studies.
The photocatalytic removal of humic acid (HA) using TiO2 under UVA irradiation was examined by monitoring changes in the UV(254) absorbance, dissolved organic carbon (DOC) concentration, apparent molecular weight distribution, and trihalomethane formation potentials (THMFPs) over treatment time. A resin fractionation technique in which the samples were fractionated into four components: very hydrophobic acids (VHA), slightly hydrophobic acids, hydrophilic charged (CHA) and hydrophilic neutral (NEU) was also employed to elucidate the changes in the chemical nature of the HA components during treatment. The UVA/TiO2 process was found to be effective in removing more than 80% DOC and 90% UV(254) absorbance. The THMFPs of samples were decreased to below 20 microg l(-1) after treatments, which demonstrate the potential to meet increasingly stringent regulatory level of trihalomethanes in water. Resin fractionation analysis showed that the VHA fraction was decreased considerably as a result of photocatalytic treatments, forming CHA intermediates which were further degraded with increased irradiation time. The NEU fraction, which comprised of non-UV-absorbing low molecular weight compounds, was found to be the most persistent component.


Analysis of flagellar protein ubiquitination.
Flagella/cilia are conserved organelles existing in unicellular protists and multicellular animals, where they perform essential motile and sensory functions. Their assembly and disassembly are coordinated with the cell cycle, and recent evidence shows that posttranslational modifications such as phosphorylation, methylation, and ubiquitination are involved in these two processes, perhaps through interacting with intraflagellar transport (IFT), a specialized intracellular transport that is required for the assembly and maintenance of flagella/cilia. In this chapter, we summarize the components of the ubiquitination system published in proteomic databases of flagella/cilia. Furthermore, we describe procedures to analyze the ubiquitin-conjugating system in Chlamydomonas flagella and to analyze flagellar protein ubiquitination during flagellar shortening and the mating process. These results and tools will be valuable for the characterization of substrates of ubiquitination and their roles in flagellar disassembly and in regulating signal transduction pathways in flagella/cilia.