The hippocampal-prefrontal pathway: the weak link in psychiatric disorders?
While the hippocampal formation and the prefrontal cortex each have a well-established role in cognitive and mnemonic processes, the extent and manner in which these structures interact to achieve these functions has not been fully delineated. Recent research in rodents compellingly supports the idea that the projection of neurons extending from the CA1 region of the hippocampus and from the subiculum to the prefrontal cortex, referred to here as the H-PFC pathway, is critically involved in aspects of cognition related to executive function and to emotional regulation. Concurrently, it is becoming evident that persons suffering from schizophrenia, depression, and post-traumatic stress disorder display structural anomalies and aberrant functional coupling within the hippocampal-prefrontal circuit. Considering that these disorders involve varying degrees of cognitive impairment and emotional dysregulation, dysfunction in the H-PFC pathway might therefore be the common element of their pathophysiology. This overlap might also be intertwined with the pathway's evident susceptibility to stress and with its relationship to the amygdala. In consequence, the H-PFC pathway is a potentially crucial element of the pathophysiology of several psychiatric diseases, and it offers a specific target for therapeutic intervention, which is consistent with the recent emphasis on reframing psychiatric diseases in terms of brain circuits.


Genetic microsurgery by laser: establishment of a clonal population of rat kangaroo cells (PTK2) with a directed deficiency in a chromosomal nucleolar organizer.
An ultraviolet laser beam was focused to a submicron spot on one of the nucleolar organizer regions of mitotic chromosomes of rat kangaroo cells in tissue culture. The daughter cells were isolated and cloned into a viable population that maintained the directed nucleolar deficiency. It is concluded that the laser can be used to delete preselected genetic regions and the genetic deletion is maintained as a heritable deficiency in subsequent daughter cells.


Characterization and overexpression of a glycosyl hydrolase family 16 beta-agarase YM01-1 from marine bacterium Catenovulum agarivorans YM01T.
Agar, usually extracted from seaweed, has a wide variety of industrial applications due to its gelling and stabilizing characteristics. Agarases are the enzymes which hydrolyze agar into agar oligosaccharides. The produced agar oligosaccharides have been widely used in cosmetic, food, and medical fields due to their biological functions. A beta-agarase gene, YM01-1, was cloned and expressed from a marine bacterium Catenovulum agarivorans YM01T. The encoding agarase of YM01-1 consisted of 331 amino acids with an apparent molecular mass of 37.7 kDa and a 23-amino-acids signal peptide. YM01-1 belongs to glycoside hydrolase 16 (GH16) family based on the amino acid sequence homology. The optimum pH and temperature for its activity was 7.0 and 50 °C, respectively. YM01-1 was stable at a pH of pH 6.0-9.0 and temperatures below 45 °C. Thin layer chromatography (TLC) and ion trap mass spectrometer of the YM01-1 hydrolysis products displayed that YM01-1 was an endo-type β-agarase and degrades agarose, neoagarohexaose, neoagarotetraose into neoagarobiose. The Km, Vmax, Kcat and Kcat/Km values of the YM01-1 for agarose were 8.69 mg/ml, 4.35 × 103 U/mg, 2.4 × 103 s-1 and 2.7 × 106 s-1 M-1, respectively. Hence, the enzyme with high agarolytic activity and single end product was different from other GH16 agarases, which has potential applications for the production of oligosaccharides with remarkable activities.


Contributions of cellular and paracellular pathways to transepithelial intestinal calcium transport.
The small intestine may supply adequate levels of nutritionally required calcium in the absence of stimulated (1,25(OH)2-D3) cell-mediated mechanism of absorption if dietary calcium levels are sufficiently high. This same route may also account for net loss of systemic calcium due to asymmetrical paracellular calcium secretion in the absence of sufficient dietary calcium. Fine adjustments in net calcium balance may occur in the large intestine where inefficiencies of paracellular leaks are significantly reduced and larger calcium gradients can be sustained.


A novel wavelet decomposition and transformation convolutional neural network with data augmentation for breast cancer detection using digital mammogram.
Research in deep learning (DL) has continued to provide significant solutions to the challenges of detecting breast cancer in digital images. Image preprocessing methods and architecture enhancement techniques have been proposed to improve the performance of DL models such as convolutional neural networks (CNNs). For instance, the wavelet decomposition function has been used for image feature extraction in CNNs due to its strong compactness. Additionally, CNN architectures have been optimized to improve the process of feature detection to support the classification process. However, these approaches still lack completeness, as no mechanism exists to discriminate features to be enhanced and features to be eliminated for feature enhancement. More so, no studies have approached the use of wavelet transform to restructure CNN architectures to improve the detection of discriminant features in digital mammography for increased classification accuracy. Therefore, this study addresses these problems through wavelet-CNN-wavelet architecture. The approach presented in this paper combines seam carving and wavelet decomposition algorithms for image preprocessing to find discriminative features. These features are passed as input to a CNN-wavelet structure that uses the new wavelet transformation function proposed in this paper. The CNN-wavelet architecture applied layers of wavelet transform and reduced feature maps to obtain features suggestive of abnormalities that support the classification process. Meanwhile, we synthesized image samples with architectural distortion using a generative adversarial network (GAN) model to argue for their training datasets' insufficiency. Experimentation of the proposed method was carried out using DDSM + CBIS and MIAS datasets. The results obtained showed that the new method improved the classification accuracy and lowered the loss function values. The study's findings demonstrate the usefulness of the wavelet transform function in restructuring CNN architectures for performance enhancement in detecting abnormalities leading to breast cancer in digital mammography.


Testing for collective choices in the two-spotted spider mite.
Silk is a vector for collective behaviour in many spinning arthropods, including social spiders, social caterpillars, and some spider mites. In this study, the potential for silk-mediated collective choices is evaluated for the two-spotted spider mite Tetranychus urticae. This subsocial mite lives in large colonies on plants, sheltered under a collectively spun silk web. The silk has an attractive and arresting effect. We test whether the silk trails left by the spider mites can give rise to the collective choice of a path. The experiment consists in offering two identical paths to a group of migrating mites. Our results show that the presence of a silk trail influences the mites, but not sufficiently to systematically provoke a collective choice. In order to determine the trail following potential of T. urticae, we parameterise a theoretical trail following model to fit our experiments and those found in the literature. Our prediction is that even after a large number of mites have passed (200), a systematic collective choice of path should not be expected under the tested conditions. Our results, combined with what is known from the literature, allow us to propose a general scenario for the dispersal behaviour of T. urticae.


Patch testing with the European baseline series fragrance markers: a 2016 update.
Fragrance contact allergy is common and is currently screened for using the following European baseline series fragrance markers: fragrance mix (FM)I, FMII, Myroxylon pereirae and hydroxyisohexyl 3-cyclohexene carboxaldehyde. To investigate the validity of patch testing using these fragrance markers in detecting fragrance allergy to 26 individual fragrance substances for which cosmetic ingredient labelling is mandatory within the European Union. We conducted a retrospective review of the patch test records of all patients with eczema who underwent testing using the European baseline series, extended with the individual fragrance substances during the period from 2015 to 2016. Overall, 359 patients (17·2%) reacted to one or more allergens from the labelled fragrance substance series and/or a fragrance marker from the European baseline series. The allergens that were positive with the greatest frequencies were oxidized linalool [n = 154; 7·4%, 95% confidence interval (CI) 6·3-8·6], oxidized limonene (n = 89; 4·3%, 95% CI 3·4-5·2) and Evernia furfuracea (n = 44; 2·1%, 95% CI 1·5-2·8). Of the 319 patients who reacted to any of the labelled fragrance substances, only 130 (40·8%) also reacted to a baseline series fragrance marker. The sensitivity of our history-taking for detecting fragrance allergy was 25·7%. Given the evolving trends in fragrance allergy, patch testing with FMI, FMII, M. pereirae and hydroxyisohexyl 3-cyclohexene carboxaldehyde is no longer sufficient for screening for fragrance allergy.


Short-term outcomes of laparoscopic approach to colonic obstruction for colon cancer.
We speculated that a laparoscopic approach to emergent/urgent partial colectomy for colonic obstruction would be associated with less morbidity and shorter length of stay with similar mortality to open colectomy. We compared the outcomes of laparoscopic and open approaches to emergent/urgent partial colectomy for colonic obstruction from colonic cancer using data from the National Surgical Quality Improvement Program (NSQIP) database for the period of 2012-2017. Multivariate analysis compared NSQIP data points following laparoscopic, laparoscopic converted to open, and open colectomy for emergent/urgent colectomy for colonic obstruction from colon cancer from 2012 to 2017. A total of 1293 patients who underwent emergent colectomy for colon obstruction from colon cancer during 2012-2017 were identified within the NSQIP database. Laparoscopic approach was used for colonic obstruction in 19.3% of operations with a conversion rate of 28.5%. A laparoscopic approach to obstructing colonic cancers was associated with lower morbidity (50% vs. 61.8%, AOR: 0.67, P = 0.01) and shorter hospitalization length (10 days vs. 13 days, mean difference: 3 days, P < 0.01) compared with an open approach. However, the mean operation duration was longer in laparoscopic operations than open operations (159 min vs. 137 min, P < 0.01). A laparoscopic approach to malignant colonic obstruction is associated with decreased morbidity. This suggests that efforts should be directed towards increasing the utilization of laparoscopic approaches for the surgical treatment of colonic obstruction.


Perianesthesia Nurses Pain Management Practices: Findings and Recommendations From a National Descriptive Study of Members of the American Society of Perianesthesia Nurses.
The purpose of this study was to identify current individual practice of perianesthesia nurses regarding assessment and documentation of pain. Descriptive cross-sectional design using vignette technique. Vignettes with questions available via electronic survey offered to attendees of the 2017 American Society of PeriAnesthesia Nurses National Conference. Total of 1,680 perianesthesia nurses participated; 41.4% reported assessment of pain compared with 36.7% who reported documentation of pain assessment. The numeric (0 to 10) pain intensity score was the most commonly used assessment method. Only 16.4% assessed for and documented pain location, 14.4% assessed for and documented quality of pain. Pain assessment should include intensity, location, quality, and functional impact. The gap between nurses' practices in assessment and documention of pain may be related to system barriers. Embedding evidence-based best practice within electronic health records may improve both. Prior literature, as well as our findings, indicate these trends (missed documentation and assessment) are more global than only perianesthesia nursing.


Synaptic excitation produces a long-lasting rebound potentiation of inhibitory synaptic signals in cerebellar Purkinje cells.
Persistent changes in synaptic efficacy are thought to underlie the formation of learning and memory in the brain. High-frequency activation of an afferent excitatory fibre system can induce long-term potentiation, and conjunctive activation of two distinct excitatory synaptic inputs to the cerebellar Purkinje cells can lead to long-term depression of the synaptic activity of one of the inputs. Here we report a new form of neural plasticity in which activation of an excitatory synaptic input can induce a potentiation of inhibitory synaptic signals to the same cell. In cerebellar Purkinje cells stimulation of the excitatory climbing fibre synapses is followed by a long-lasting (up to 75 min) potentiation of gamma-aminobutyric acid A (GABAA) receptor-mediated inhibitory postsynaptic currents (i.p.s.cs), a phenomenon that we term rebound potentiation. Using whole-cell patch-clamp recordings in combination with fluorometric video imaging of intracellular calcium ion concentration, we find that a climbing fibre-induced transient increase in postsynaptic calcium concentration triggers the induction of rebound potentiation. Because the response of Purkinje cells to bath-applied exogenous GABA is also potentiated after climbing fibre-stimulation with a time course similar to that of the rebound potentiation of i.p.s.cs, we conclude that the potentiation is caused by a calcium-dependent upregulation of postsynaptic GABAA receptor function. We propose that rebound potentiation is a mechanism by which in vivo block of climbing fibre activity induces an increase in excitability in Purkinje cells. Moreover, rebound potentiation of i.p.s.cs is a cellular mechanism which, in addition to the long-term depression of parallel fibre synaptic activity, may have an important role for motor learning in the cerebellum.


Comparative study on conformational stability and subunit interactions of two bacterial asparaginases.
The denaturation and reconstitution of Erwinia carotovora and Escherichia coli L-asparaginases has been followed by optical rotatory dispersion, circular dichroism and analytical ultracentrifugation. Denaturation in urea results in dissociation of the native enzyme (mol. wt. 140 000 approx.) to produce unfolded subunits (mol. wt. 35 000 approx.); the Erwinia L-asparaginase subunits can be refolded by dilution or dialysis in alkaline conditions, pH 10.5, without aggregation to the active tetramer, to give a rather unstable solution of a monomer possibly in equilibrium with dimer. These alkaline-reconstituted subunits undergo a conformational change to a more ordered state in the presence of sodium dodecylsulphate, similar to those produced by the action of sodium dodecylsulphate on the native enzyme. If the denatured subunits are reconstituted in the pH range 5.0-7.5, the enzymically active tetramer is reformed in up to 80% yield, depending upon the conditions of temperature and concentration. Kinetic data for these various transitions suggest that dissociation is a rate-limiting step while conformational changes of the polypeptide chains are relatively much more rapid. The possible significance of these different rates of change to therapeutic considerations is discussed.


Phospholipase activity in human tumors: localization by cytochemical staining.
Phospholipase activity was localized for the first time by cytochemical staining at the plasma membrane of malignant cells in gastric adenocarcinomas by electron microscopy. This activity was not found in benign cells of the same tumor, e.g., in components of the connective tissue underlying the glandular epithelium, or in cells beyond the margin of the same tumor. Neither benign nor malignant cells of colorectal tumors, nor those in malignant melanoma, had any phospholipase activity that could be demonstrated by the method.


Pulmonary Rehabilitation in a Patient With Bronchiectasis and Underlying Cerebral Palsy: A Case Presentation.
Bronchiectasis is a chronic pulmonary disease characterized by the permanent dilatation of the airways, with recurrent infections. As the disease progresses, extrapulmonary symptoms manifest. If the patient with bronchiectasis has an underlying central nervous system disease such as cerebral palsy (CP), extrapulmonary functions decline faster. The co-occurrence of these 2 diseases may make care more complex, and there have been no reports about pulmonary rehabilitation (PR) in this class of patients. Here, we present a patient with bronchiectasis and underlying CP who showed marked improvement of pulmonary function and clinical symptoms after 6 weeks of a patient-specific intensive PR program. IV.


Alterations of diffusion tensor MRI parameters in the brains of patients with Parkinson's disease compared with normal brains: possible diagnostic use.
To investigate the diagnostic performance of diffusion tensor imaging in patients with Parkinson's disease (PD). We examined a total of 126 PD patients (68 males/58 females, mean age: 62.0 ±7.6 years) and 91 healthy controls (43 males/48 females, mean age: 59.8 ±7.2 years). Images were acquired on a 3 Tesla magnetic resonance scanner. The Camino software was used to normalize and parcellate diffusion-weighted images into 90 cerebral regions based on the automatic anatomical labelling template. The minimum, median, and maximum values of the mean/radial/axial diffusivity/fractional anisotropy were determined. The diagnostic performance was assessed by receiver operating characteristic analysis. The associations of imaging parameters with disease severity were tested using Pearson's correlation coefficients after adjustment for disease duration. Compared with healthy controls, PD patients showed increased diffusivity in multiple cortical regions that extended beyond the basal ganglia. An area under curve of 85 % was identified for the maximum values of mean diffusivity in the ipsilateral middle temporal gyrus. The most significant intergroup difference was 26.8 % for the ipsilateral inferior parietal gyrus. The measurement of water diffusion from the parcellated cortex may be clinically useful for the assessment of PD patients. • Increased diffusivity was identified in multiple cortical regions of Parkinson's disease patients. • The area under the receiver operating curve was 85 % in the middle temporal gyrus. • The ipsilateral inferior parietal gyrus showed the most significant change.


Cancer combination therapies by angiogenesis inhibitors; a comprehensive review.
Abnormal vasculature is one of the most conspicuous traits of tumor tissue, largely contributing to tumor immune evasion. The deregulation mainly arises from the potentiated pro-angiogenic factors secretion and can also target immune cells' biological events, such as migration and activation. Owing to this fact, angiogenesis blockade therapy was established to fight cancer by eliminating the nutrient and oxygen supply to the malignant cells by impairing the vascular network. Given the dominant role of vascular-endothelium growth factor (VEGF) in the angiogenesis process, the well-known anti-angiogenic agents mainly depend on the targeting of its actions. However, cancer cells mainly show resistance to anti-angiogenic agents by several mechanisms, and also potentiated local invasiveness and also distant metastasis have been observed following their administration. Herein, we will focus on clinical developments of angiogenesis blockade therapy, more particular, in combination with other conventional treatments, such as immunotherapy, chemoradiotherapy, targeted therapy, and also cancer vaccines. Video abstract.


TRAP-induced platelet aggregation is enhanced in cardiovascular patients receiving dabigatran.
Novel (or non-vitamin K antagonist) oral anti-coagulants (NOACs) are antagonists of coagulation factors (F) Xa (rivaroxaban) or IIa (dabigatran), and their non-inferiority compared with vitamin K antagonists has been demonstrated in patients with non-valvular atrial fibrillation. However, it is still not fully understood if and how dabigatran and rivaroxaban impact platelet function. This observational study aimed to assess platelet function in patients receiving dabigatran or rivaroxaban. This was a single centre, observational study quantifying platelet aggregation in 90 patients treated with NOACs by multiple electrode aggregometry. The thrombin receptor activating peptide (TRAP)-induced platelet aggregation was significantly higher in 35 patients receiving dabigatran (d) compared with control (c) patients (d 108±31 vs. c 85±30arbitrary units [AU]∗min, p<0.001). Patients receiving rivaroxaban (r) showed no differences compared with the control group (r 88±32 vs. c 85±30AU∗min, p=0.335). In intraindividual time courses of 16 patients, a significantly higher aggregation was found after the administration of dabigatran (before vs. after; 83±29 vs. 100±31AU∗min, p=0.009). In this observational study, the TRAP-induced platelet aggregation was enhanced in cardiovascular patients receiving dabigatran. This might be explained by a change in the expression profile of thrombin receptors on the surface of platelets. Rivaroxaban had no influence on platelet aggregation.


Evening types as determined by subjective and objective measures are more emotional eaters.
This study aimed to determine the association between being an evening type (ET; defined subjectively by the Morning-Evening Questionnaire or objectively by the dim-light melatonin onset [DLMO] timing) and reporting emotional eating (EE) behaviors. Cross-sectional analyses were conducted in 3964 participants (four international cohorts: ONTIME and ONTIME-MT [both Spain], SHIFT [the US], and DICACEM [Mexico]), in which chronotype (Morning-Evening Questionnaire), EE behaviors (Emotional Eating Questionnaire), and dietary habits (dietary records or food-frequency questionnaire) were assessed. Among 162 participants (ONTIME-MT subsample), additional measures of DLMO (physiological gold standard of circadian phase) were available. In three populations, ETs presented with a higher EE score than morning types (p < 0.02); and they made up a higher proportion of emotional eaters (p < 0.01). ETs presented with higher scores on disinhibition/overeating as well as food craving factors and experienced these behaviors more frequently than morning types (p < 0.05). Furthermore, a meta-analysis showed that being an ET was associated with a higher EE score by 1.52 points of a total of 30 points (95% CI: 0.89-2.14). The timing of DLMO in the early, intermediate, and late objective chronotypes occurred at 21:02 h, 22:12 h, and 23:37 h, with late types showing a higher EE score (p = 0.043). Eveningness associated with EE in populations with different cultural, environmental, and genetic backgrounds. Individuals with late DLMO also showed more EE.


Chemical exposure levels in printing and coating workers with cholangiocarcinoma (third report).
This study aimed to identify the chemicals used by five printing workers and one coating worker who developed cholangiocarcinoma and estimate the workers' levels of chemical exposure. We obtained information on chemicals from the Ministry of Health, Labour and Welfare, Japan, and estimated working environment concentrations of the chemicals in printing and coating rooms and exposure concentrations during the ink and dirt removal processes. We also calculated shift time-weighted averages of exposure concentrations. All five printing workers were exposed to both 1,2-dichloropropane (1,2-DCP) and dichloromethane (DCM). The estimated maximum exposure concentrations for each of the five workers were 190 to 560 ppm for 1,2-DCP and 300 to 980 ppm for DCM, and the estimated shift average exposure concentrations were 0 to 230 ppm for 1,2-DCP and 20 to 470 ppm for DCM. The coating worker was exposed to 1,2-DCP, but not DCM. He did not use ink, and thus was subjected to different conditions than the printing workers. The estimated maximum exposure concentration of 1,2-DCP was 150 ppm, and the estimated shift time-weighted average exposure concentration was 5 to 19 ppm. Our findings support the notion that 1,2-DCP contributes to the development of cholangiocarcinoma in humans and the notion that DCM may also be a contributing factor. The finding that the coating worker was exposed to 1,2-DCP at a lower exposure concentration is important for determining the occupational exposure limit. Furthermore, the subject did not use ink, which suggests that ink did not contribute to the development of cholangiocarcinoma.


A nursing intervention to enhance the self-care capacity of nondisclosed persons living with HIV in Thailand.
Significant numbers of nondisclosed persons living with HIV (NPLWH) who are aware of their status do not enter care and must rely on their own abilities to maintain their health. This study shows how these individuals can be reached through nongovernmental organizations and assisted to improve their self-care capacity through an intensive nursing intervention. NPLWH in Chiang Mai, Thailand, were assessed using a 31-item self-care capacity questionnaire (range = 0-62) at baseline and monthly for 6 months. The nursing intervention used reflective questioning to assist PLWH to find ways to improve their self-care capacity. At baseline, the mean self-care capacity score was 31.4. After 3 months of intervention, the score increased to 54 and was maintained at this level for the next 3 months. This study demonstrates that nurses can reach out to NPLWH who are not in care and help to improve self-care capacity.


Prevalence, correlates, comorbidities, and suicidal tendencies of premenstrual dysphoric disorder in a nationwide sample of Korean women.
We examined the prevalence, correlates, comorbidities, and suicidal tendencies of premenstrual dysphoric disorder (PMDD) according to the DSM-IV criteria in a nationwide sample of Korean women. A total of 2,499 women aged 18-64 years participated in this study. Diagnostic assessments were based on the Korean version of the Composite International Diagnostic Interview (CIDI) 2.1 and its 12-month PMDD diagnostic module, which were administered by lay interviewers. The frequencies of DSM-IV psychiatric disorders, insomnia, and suicidal tendency were analyzed among PMDD cases and compared with non-PMDD cases, and both odds ratios and significance levels were calculated. The 12-month prevalence rate of DSM-IV-diagnosed PMDD was 2.4 %. Among subjects with PMDD, 59.3 % had at least one psychiatric illness; in comparison, the control frequency was 21.8 %. Associations between PMDD and alcohol abuse/dependence, major depressive disorder, post-traumatic stress disorder, social phobia, specific phobia, somatoform disorder, insomnia, and suicidality were overwhelmingly positive and significant (p < 0.05), after controlling for age. Physical illness and being underweight were associated with increased risks of PMDD (p < 0.05). PMDD was prevalent in the nationwide sample of Korean women and was frequently associated with other psychiatric disorders, insomnia, and suicidality, suggesting the need to detect and treat women who experience PMDD.


Postconditioning the human heart.
In animal models, brief periods of ischemia performed just at the time of reperfusion can reduce infarct size, a phenomenon called postconditioning. In this prospective, randomized, controlled, multicenter study, we investigated whether postconditioning may protect the human heart during coronary angioplasty for acute myocardial infarction. Thirty patients, submitted to coronary angioplasty for ongoing acute myocardial infarction, contributed to the study. Patients were randomly assigned to either a control or a postconditioning group. After reperfusion by direct stenting, control subjects underwent no further intervention, whereas postconditioning was performed within 1 minute of reflow by 4 episodes of 1-minute inflation and 1-minute deflation of the angioplasty balloon. Infarct size was assessed by measuring total creatine kinase release over 72 hours. Area at risk and collateral blood flow were estimated on left ventricular and coronary angiograms. No adverse events occurred in the postconditioning group. Determinants of infarct size, including ischemia time, size of the area at risk, and collateral flow, were comparable between the 2 groups. Area under the curve of creatine kinase release was significantly reduced in the postconditioning compared with the control group, averaging 208 984+/-26 576 compared with 326,095+/-48,779 (arbitrary units) in control subjects, ie, a 36% reduction in infarct size. Blush grade, a marker of myocardial reperfusion, was significantly increased in postconditioned compared with control subjects: 2.44+/-0.17 versus 1.95+/-0.27, respectively (P<0.05). This study suggests that postconditioning by coronary angioplasty protects the human heart during acute myocardial infarction.


Death risk factor analysis in primary hyperparathyroidism.
Patients treated for primary hyperparathyroidism run an increased risk of death. The aim of this study was to analyse several factors that may influence their risk of death. General, laboratory, physical and clinical variables, altogether 34 variables, were defined as possible risk factors for death and were studied in a patient series of 845 patients operated on during the period 1953-82. Mean follow-up time was 10.5 years (SD 5.9); 253 patients were deceased at follow-up. Cox's proportional hazard model was used. We found seven variables with independent influence on the risk of death: age, sex, diabetes, cardiovascular disease, glomerular filtration rate, renal tubular concentration capacity and amount of diseased parathyroid tissue. The remaining 27 variables were separately tested, one at a time, using the same method and with the influence of age and sex eliminated. In this test situation, the year of surgery, peak serum calcium, serum creatinine level, body mass index, hypertension, psychiatric symptoms and a history of crisis were all significantly related to the risk of death. The analyses also gave information on the direction and magnitude of the effect of the variables on the risk of death. Primary hyperparathyroidism itself is a risk factor for death, but it was concluded that well-preserved renal function at surgery seems to have a protective role. We also found that the greater the amount of diseased parathyroid tissue the lesser the renal function and, furthermore, that hyperparathyroidism of substantial degree or long duration may bring about renal impairment that is not necessarily disclosed by the creatinine value alone.


The Effect of Chronic Preoperative Opioid Use on Surgical Site Infections, Length of Stay, and Readmissions.
Chronic opioid use in the United States is a well-recognized public health concern with many negative downstream consequences. Few data exist regarding the use of preoperative opioids in relation to outcomes after elective colorectal surgery. The purpose of this study was to determine if chronic opioid use before colorectal surgery is associated with a detriment in postoperative outcomes. This is a retrospective review of administrative data supplemented by individual chart review. This study was conducted in a single-institution, multisurgeon, community colorectal training practice. All patients undergoing elective colorectal surgery over a 3-year time frame (2011-2014) were selected. Opioid use was stratified based on total dose of morphine milligram equivalents (naive, sporadic use (>0-15 mg/day), regular use (>15-45 mg/day), and frequent use (>45 mg/day)). Primary outcomes were surgical site infections, length of hospital stay, and readmissions. Of the 923 patients, 23% (n = 213) were using opioids preoperatively. The preoperative opioid group contained more women (p = 0.047), underwent more open surgery (p = 0.003), had more nonmalignant indications (p = 0.013), and had a higher ASA classification (p = 0.003). Although median hospital stay was longer (4.7 days vs 4.0, p < 0.001), there was no difference in any surgical site infections (10.3% vs 7.1%, p = 0.123) or readmissions (14.2% vs 14.1%, p=0.954). Multivariable analysis identified preoperative opioid use (17.0% longer length of stay; 95% CI, 6.8%-28.2%) and ASA 3 or 4 (27.2% longer length of stay; 95% CI, 17.1-38.3) to be associated with an increase in length of stay. Retrospectively abstracted opioid use and small numbers limit the conclusions regarding any dose-related responses on outcomes. Although preoperative opioid use was not associated with an increased rate of surgical site infections or readmissions, it was independently associated with an increased hospital length of stay. Innovative perioperative strategies will be necessary to eliminate these differences for patients on chronic opioids. See Video Abstract at http://links.lww.com/DCR/B280. EFECTOS DEL CONSUMO CRÓNICO DE OPIOIDES EN EL PREOPERATORIO CON RELACIÓN A LAS INFECCIONES DE LA HERIDA QUIRÚRGICA, LA DURACIÓN DE LA ESTADÍA Y LA READMISIÓN: El consumo crónico de opioides en los Estados Unidos es un problema de salud pública bien reconocido a causa de sus multiples consecuencias negativas ulteriores. Existen pocos datos sobre el consumo de opioides en el preoperatorio relacionado con los resultados consecuentes a una cirugía colorrectal electiva.El propósito es determinar si el consumo crónico de opioides antes de la cirugía colorrectal se asocia con un detrimento en los resultados postoperatorios.Revisión retrospectiva de datos administrativos complementada por la revisión de un gráfico individual.Ejercicio durante la formación de multiples residentes en cirugía colorrectal enTodos los pacientes de cirugía colorrectal electiva durante un período de 3 años (2011-2014).El uso de opioides se estratificó en función de la dosis total de equivalentes de miligramos de morfínicos (uso previo, uso esporádico [> 0-15 mg / día], uso regular (> 15-45 mg / día) y uso frecuente (> 45 mg / día)). Los resultados primarios fueron las infecciones de la herida quirúrgica, la duración de la estadía hospitalaria y la readmisión.De los 923 pacientes, el 23% (n = 213) consumían opioides antes de la operación. El grupo con opioides preoperatorios tenía más mujeres (p = 0.047), se sometió a una cirugía abierta (p = 0.003), tenía mas indicaciones no malignas (p = 0.013) y tenía una clasificación ASA más alta (p = 0.003). Aunque la mediana de la estadía hospitalaria fue más larga (4,7 días frente a 4,0; p <0,001), no hubo diferencia en ninguna infección de la herida quirúrgica (10,3% frente a 7,1%, p = 0,123) o las readmisiones (14,2% frente a 14,1%, p = 0,954). El análisis multivariable identificó que el uso de opioides preoperatorios (17.0% más larga LOS; IC 95%: 6.8%, 28.2%) y ASA 3 o 4 (27.2% más larga LOS; IC 95%: 17.1, 38.3) se asocia con un aumento en LOS.La evaluación retrospectiva poco precisa del consumo de opioides y el pequeño número de casos limitan las conclusiones sobre cualquier respuesta relacionada con la dosis - resultado.Si bien el consumo de opioides preoperatorios no se asoció con un aumento en la tasa de infecciones de la herida quirúrgica o las readmisiones, ella se asoció de forma independiente con un aumento de la LOS hospitalaria. Serán necesarias estrategias perioperatorias innovadoras para eliminar estas diferencias en los pacientes consumidores cronicos de opioides. Consulte Video Resumen en http://links.lww.com/DCR/B280.


Biobleach boosting effect of recombinant xylanase B from the hyperthermophilic Thermotoga maritima on wheat straw pulp.
The recombinant xylanase B (XynB) of Thermotoga maritima MSB8 was found to be highly specific towards xylans and exhibit very low activity towards carboxymethylcellulose in previous study. XynB was thermostable at neutral to alkaline pH region at 90 degrees C and retained more than 90% activity after 1 h over the pH range of pH 6.1 to 11.1. The suitability of XynB for use in the biobleaching of wheat straw pulp was investigated. Pretreatment of the pulp with XynB resulted in a substantial improvement in the bleachability of wheat straw pulp. When XynB at 10 U g(-1) was used to treat wheat straw pulp, it reduced pulp kappa number by 1.1 point, enhanced pulp brightness by 5.5% (% ISO) and improved other pulp properties, such as tensile index and breaking length. Biobleaching of wheat straw pulp with XynB saved active chlorine up to 34.5% while still maintaining the brightness at the control level. Besides, pretreatment of pulp with XynB was also effective at an alkaline pH as high as pH 10.1. This is the first report on the potential application of XynB from T. maritima MSB8 in the pulp and paper sector.


How effective is advanced training concerning depression and suicidality among the elderly? Results of a pilot study.
Three Hundred and Seventy Four geriatric caregivers in Nuremberg and Munich participated in a four-hour advanced in-house training addressing the topic. "depression and suicidality in old age." Geriatric caregivers are key persons in early diagnosis of depressive symptoms and suicidality. The training focused on qualifying and sensitizing caregivers for these topics. A 12-item questionnaire was applied to measure the outcome parameters "knowledge and attitudes towards depression and suicidality in old age" within a pre-, post-, Three-months-follow-up design (rate of return = 58%). Short-term effectiveness of the advanced training "depression in old age" could be shown for most of the items. Significant long-term effects could be found concerning increase of knowledge about pharmacotherapy with antidepressants. Attitude towards "suicide in old age" also changed significantly. The training program was effective in improving knowledge and attitudes of geriatric caregivers concerning depression and suicidality.


Anti-D and anti-i activities are inseparable in V4-34-encoded monoclonal anti-D: the same framework 1 residues are required for both reactivities.
The heavy-chain V4-34 germline gene segment is mandatory for pathologic cold-reacting autoantibodies with anti-I/i specificity (cold agglutinins) and is also preferentially used by monoclonal immunoglobulin M alloantibodies against D and other Rh antigens. The use of the V4-34 segment by monoclonal anti-D has previously been shown to also confer anti-I/i reactivity (cold agglutinin activity), which has implications for the use of such antibodies for Rh blood typing. V4-34 framework 1 (FR1) sequence is believed to be critical for cold agglutinin activity of cold agglutinins. The aim of this investigation was to use site-directed mutagenesis of a recombinant V4-34-encoded anti-D to determine the contribution of V4-34 FR1 sequence to anti-D activity and whether mutational modifications in the FR1 region could separately alter anti-D and anti-i activities. The results show that amino acid changes in V4-34 FR1 at W7, A23, and Y25 have a profound effect on anti-D activity as well as on anti-i activity. It was not possible to substantially reduce or remove anti-i activity without reducing anti-D activity to a comparable extent. The same nonpolar hydrophobic amino acids in FR1 are critical for maintaining both anti-D and anti-i activity. It is proposed that these residues influence the conformation of the antigen-binding site.


CT of intracerebral haemorrhage due to mycotic aneurysms--case report.
The CT findings in a case of intracerebral haematoma due to rupture of a mycotic aneurysm are presented. In addition to the haematoma, CT demonstrated small focal areas of cortical enhancement, which corresponded to the peripheral aneurysms seen on angiography. Such findings are thought to be characteristic; a brief differential diagnosis is discussed.


Fetal lung growth: influence of maternal exposure to cold and exercise in rats.
The consequences of maternal exposure to low ambient temperature and exercise on maternal and fetal lung growth and in particular on the relationship between the three gas exchange organs (lungs and placenta) were studied in albino rats. Pregnant rats were subjected to 10 degrees C ambient temperature or to daily 10 min swimming exercise beginning at day 3 or day 11 of pregnancy till day 21 when they were sacrificed. Maternal lung growth was assessed by measuring the lung weight, lung air volume and lung DNA content, and the fetal lung growth by lung DNA content. Comparisons were made in rats with litter sizes of 9-14. The major findings were as follows. Cold increased: (1) the maternal lung, liver, kidney and heart size, and fetal body weight, in both groups, but to a greater degree in rats exposed to cold at day 3; and (2) fetal lung DNA content in rats subjected to cold at late gestation. It abolished the relationship between maternal and fetal lung DNA content which exists in large litter size pregnancies. Exercise did not enlarge the maternal lungs; it decreased the placental weight and fetal lung DNA content and abolished the relationship between maternal and fetal lung DNA content in rats subjected to exercise at early gestation. Neither cold nor exercise had an effect on fetal lung maturation. It is postulated that reduction in fetal lung DNA content with maternal exercise may result from the effects of hypoxemia which may be the consequence of reduced uterine blood flow; and that abolition of normally existing direct relationship between maternal and fetal lung DNA content may be the outcome of the effects of alterations in metabolic and endocrine functions, in both the mother and the fetus, in response to cold temperature and exercise, offsetting the influence the growing maternal lung may have on fetal lung growth.


Erratum: Bilateral patellar fractures and increased cortical bone thickness associated with long-term oral alendronate treatment in a cat.
[This corrects the article DOI: 10.1177/2055116917727137.].


Distributed treatment systems.
This section presents a review of the scientific literature published in 2019 on topics relating to distributed treatment systems. This review is divided into the following sections: constituent removal, treatment technologies, planning and treatment management, and other topics. PRACTITIONER POINTS: Highlights changes and innovation in removal techniques and technologies in water treatment. Reviews management systems of distributed treatment systems. Discusses point-of-use treatment systems.


Bioceramics utilization for the repair of internal resorption of the root: A case report.
The objective of this work is displaying a successful treatment for an internal resorption case under operating microscope using bioceramic material. Periapical radiograph showed radiolucent lesion representing large internal resorption of the root. The respective defect was obturated using endoscquence bioceramic material follow up at the month 18 after treatment revealed no abnormal finings clinically and radiographically. New generations bioceramics have many advantages that internal root resorption cases can benefit from. The use of operating microscope helps to apply obturating materials with precision. However, long term study on a large sample is required in future studies.


Phorbol ester stimulates macrophage invasion of fibrin matrices.
Macrophages migrate through a fibrin-rich extracellular matrix in chronic inflammation, wound healing, and other pathophysiological processes. To investigate the factors that might influence the ability of mononuclear phagocytes to invade fibrin matrices, we cultured macrophage-like P388D1 cells as well as resident and thioglycollate-elicited mouse peritoneal macrophages on three-dimensional fibrin gels, and we examined the effect of agents known to stimulate a variety of macrophage functions, including the production of fibrinolytic enzymes. Cells grown on fibrin gels under control conditions, as well as cells treated with either bacterial lipopolysaccharide or concanavalin A, remained confined to the gel surface. In contrast, the tumor promoter 4 beta-phorbol 12-myristate 13-acetate (PMA) induced both P388D1 cells and peritoneal macrophages to invade the underlying fibrin matrix. The invasive behavior of PMA-treated P388D1 cells was not affected by protease inhibitors of various specificities. These results demonstrate that certain exogenous signals can profoundly modify the ability of macrophages to migrate through fibrin matrices.


Cardiovascular and behavioral actions of centrally administered cimetidine.
The cardiovascular and behavioral actions of cimetidine, injected into the lateral ventricle, were studied in conscious, freely moving rats. Cimetidine produced a dose-dependent pressor response accompanied by decreases in heart rate and increases in pulse pressure. At doses of 25-100 micrograms, cimetidine produced sedation; however, when 200 micrograms was injected, tremor was observed in all animals. If cimetidine was administered twice within 30 min to the same animal, tachyphylaxis in response to any of these actions was never evident. Although histamine produced similar pressor actions when administered intraventricularly, these effects were always subject to tachyphylaxis. The actions of cimetidine were not altered by central pretreatment with the H1 antagonist chlorpheniramine. A possible hypothesis of the central mechanism by which cimetidine produces these effects is discussed.


An Interleukin-1 beta (IL1B) haplotype linked with psychosis transition is associated with IL1B gene expression and brain structure.
We investigated IL1B genetic variation previously associated with risk for transition to psychosis for its association with gene expression in human post-mortem dorsolateral prefrontal cortex (DLPFC) from 74 (37 schizophrenia, 37 control) individuals and brain structure in 92 (44 schizophrenia, 48 control) living individuals. The IL1B A-G-T 'risk for psychosis transition' haplotype (rs16944|rs4848306|rs12621220) was associated with upregulation of IL1B mRNA expression in the DLPFC as well as reduced total grey matter and left middle frontal volumes and enlarged left lateral ventricular volume. Our results suggest IL1B genetic variation may confer psychosis risk via elevated mRNA expression and/or brain structure abnormalities.


Characterization of benign and metastatic vertebral compression fractures with quantitative diffusion MR imaging.
Conventional imaging techniques cannot be used to unambiguously and reliably differentiate malignant from benign vertebral compression fractures. Our hypothesis is that these malignant and benign vertebral lesions can be better distinguished on the basis of tissue apparent diffusion coefficients (ADCs). The purpose of this study was to test this hypothesis by using a quantitative diffusion imaging technique. Twenty-seven patients with known cancer and suspected metastatic vertebral lesions underwent 1.5-T conventional T1-weighted, T2-weighted, and contrast-enhanced T1-weighted imaging to identify the lesions. Diffusion-weighted images of the areas of interest were acquired by using a fast spin-echo diffusion pulse sequence with b values of 0-250 s/mm(2). The abnormal regions on the diffusion-weighted images were outlined by using the conventional images as guides, and the ADC values were calculated. On the basis of pathologic results and clinical findings, the cases were divided into two categories: benign compression fractures and metastatic lesions. The ADC values for each category were combined and plotted as histograms; this procedure was followed by statistical analysis. The patient group had 12 benign fractures and 15 metastases. The mean ADC values, as obtained from the histograms, were (1.9 +/- 0.3) x 10(-4) mm(2)/s and (3.2 +/- 0.5) x 10(-4) mm(2)/s for metastases and benign fractures, respectively. Our results indicate that quantitative ADC mapping, instead of qualitative diffusion-weighted imaging, can provide valuable information in differentiating benign vertebral fractures from metastatic lesions.


Induction of micronuclei in rat bone marrow and peripheral blood following acute and subchronic administration of azathioprine.
The frequency of micronuclei was assessed in polychromatic erythrocytes of bone marrow and in polychromatic and normochromatic erythrocytes in peripheral blood of rats following exposure to azathioprine for 28 days. This was compared with the incidence of micronuclei in bone-marrow following exposure to a single dose of azathioprine. The incidence of micronuclei in bone-marrow polychromatic erythrocytes at the maximum tolerated dose (10 mg/kg) following exposure for 28 days was 29.5/1000. The incidence of micronucleated polychromatic erythrocytes in the peripheral blood at this dose was 4.4/1000. At the maximum tolerated dose in the single-dose study (40 mg/kg) the incidence obtained at 48 h post-treatment was 15.7/1000. This supports the view that the use of animals in a subchronic toxicity study is at least as sensitive for assessing in vivo clastogenic activity as an acute study and could reduce animal usage in toxicology assessments.


Long-term effects of tripeptide Ile-Pro-Pro on osteoblast differentiation in vitro.
Bone mineralization is a result of the function of bone-forming osteoblasts. Osteoblast differentiation from their precursors is a carefully controlled process that is affected by many signaling molecules. Protein-rich food-derived bioactive peptides are reported to express a variety of functions in vivo. We studied the long-term in vitro effect of bioactive tripeptide Ile-Pro-Pro (IPP) on osteoblasts differentiated from human mesenchymal stem cells. Osteoblast bone alkaline phosphatase activity (bALP), bone-forming capacity and gene expression were investigated. Treatment with 50 microM IPP had no effect on bALP activity, but osteoblast mineralization was increased. Gene expression of beta-catenin, Cbfa1/Runx2, PTHrP, CREB-5, osteoglycin, osteocalcin, caspase-8, osteoprotegerin (OPG) and RANKL was analyzed by quantitative real-time PCR on Days 13, 17 and 20 of culture. The results indicate that IPP increased mineral formation due to enhanced cell survival and matrix formation. In addition, IPP reduced the RANKL/OPG ratio. Bioactive peptides, such as IPP, could be one method by which a protein-rich diet promotes bone integrity.


Intracranial in situ side-to-side microvascular anastomosis: principles, operative technique, and applications.
Side-to-Side microvascular anastomosis is a revascularization technique used to create an artificial conduit between two similar adjacent vessels. This technique is used for microsurgical clipping of aneurysms, when indicated. It is important to study the angiographic results, both immediate and long term, along with the clinical outcomes and indications of the procedure. Fifteen patients who had this procedure over a fourteen-year period were reviewed for patency of bypass by intra-arterial digital subtraction angiography (DSA) and computed tomographic arteriograms (CTA) and their clinical outcomes were studied. The mean age of the study group was 53.4 years and mean angiographic follow up period was 14 months. All surviving patients (14 patients) had patent anastomosis with good clinical outcomes. None of the patients developed a clinically manifested stroke due to the procedure, while one had a small asymptomatic infarct detected post operatively. This technique is a useful and durable solution for correcting critical stenosis or complete occlusion of the vessels, while clipping intracranial aneurysms.


The MdABI5 transcription factor interacts with the MdNRT1.5/MdNPF7.3 promoter to fine-tune nitrate transport from roots to shoots in apple.
Nitrate is a major nitrogen resource for plant growth and development and acts as both a crucial nutrient and a signaling molecule for plants; hence, understanding nitrate signaling is important for crop production. Abscisic acid (ABA) has been demonstrated to be involved in nitrate signaling, but the underlying mechanism is largely unknown in apple. In this study, we found that exogenous ABA inhibited the transport of nitrate from roots to shoots in apple, and the transcription of the nitrate transporter MdNRT1.5/MdNPF7.3 was noticeably reduced at the transcriptional level by ABA, which inhibited the transport of nitrate from roots to shoots. Then, it was found that the ABA-responsive transcription factor MdABI5 bound directly to the ABRE recognition site of the MdNRT1.5 promoter and suppressed its expression. Overexpression of MdABI5 inhibited ABA-mediated transport of nitrate from roots to shoots. Overall, these results demonstrate that MdABI5 regulates the transport of nitrate from roots to shoots partially by mediating the expression of MdNRT1.5, illuminating the molecular mechanism by which ABA regulates nitrate transport in apple.


Gender Facial Affirmation Surgery: Cheek Augmentation.
Cheek augmentation is frequently used in facial feminization surgery. Options for augmentation include both surgical and nonsurgical techniques, such as autologous and non-autologous injections, implants, and osteotomies. Cheek augmentation can be combined with other facial procedures. Complications of cheek augmentation include malposition, resorption, asymmetry, and unfavorable cosmetic results. Cheek augmentation should be considered as part of an overall facial feminizing plan.


Use of calcium antagonists in ventricular dysfunction.
Calcium antagonists are now widely used in a variety of cardiocirculatory disorders, many of which are associated with varying levels of depressed myocardial function. Thus, the hemodynamic effects of calcium antagonists in patients with normal as well as depressed ventricular function are clinically relevant. None of the 3 agents verapamil, nifedipine or diltiazem exerts significant negative inotropic effects in patients with relatively normal myocardial function, although increases in left ventricular end-diastolic pressure may occur with verapamil and possibly diltiazem. In a setting in which ischemia, hypertension or arrhythmias contribute to cardiac failure, all 3 agents may ameliorate myocardial decompensation if they reverse the precipitating causes. In patients with depressed myocardial function, the effects of diltiazem are not known; verapamil may depress myocardial function, especially if the ventricular filling pressure is increased. Nifedipine generally has little depressant action in this setting and usually improves cardiac function, especially if the sympathetic reflexes are intact. However, hemodynamic deterioration after nifedipine administration has been reported. Thus, the available data do not support the use of calcium antagonists as afterload-reducing agents in heart failure and suggest caution in the use of these agents in patients with impaired ventricular performance.


Treatment of vaginal agenesis with vulvoperineal fasciocutaneous flaps.
A simple surgical technique is reported for the treatment of vaginal agenesis utilizing vulvoperineal fasciocutaneous flaps based on the terminal vessels of the internal pudendal artery. Two vulvoperineal axial flaps are sutured together, skin surface opposed, then rotated posteriorly into rectovesical space. The operation has been performed on one patient, with good anatomic and functional results and without complications.


Extracranial CSF shunting for infantile non tumoral hydrocephalus--a retrospective analysis of 360 cases.
A series of 360 consecutive extracranial CSF shunts performed between June 1960 and June 1976 for infantile non tumoral hydrocephalus is reviewed. The surgical methods used, the reasons for re-operation, the time distribution of post-operative complications, the causes of death and the long term results are analysed and discussed for each of the four groups: tetraventricular communicating hydrocephalus, triventricular hydrocephalus, obstructive hydrocephalus with a ventriculo-cisternal block and post-meningocele or post-myelomeningocele hydrocephalus.


Overexpression of the glucocorticoid receptor represses transcription from hormone responsive and non-responsive promoters.
The glucocorticoid receptor (GR) is a regulable transcription factor which can bind to DNA response elements in the vicinity of inducible gene promoters and enhance the rate of transcription initiation. The concentration of endogenously expressed GR has been shown to limit the magnitude of the transcriptional induction response in cultured cells. We have investigated the consequence of increased GR expression on the transcriptional activity of a hormone responsive promoter, the MMTV LTR, and on three non-responsive promoters, the RSV LTR, the SV40 early promoter and the c-fos promoter in transiently transfected cells. Low receptor concentrations allow a slight hormonal induction of the MMTV LTR while maximal inducibility can be observed at intermediate GR concentrations. High GR expression reduces the hormonal induction on the MMTV LTR and also adversely effects transcription from the RSV LTR, the SV40 and c-fos promoters. This repression effect is dependent on GR activation. These experiments suggest that the GR interacts with a nuclear factor that is required for the activation of all four promoters. It is probable that "squelching", i.e. protein-protein complex formation in the nucleus leads to the sequestration of interacting proteins(s) essential for the transcription machinery, causing a limitation for the initiation events.


Cesarean Scar Pregnancy: Patient Counseling and Management.
There is no universally agreed upon and adopted management protocol supported by professional societies in the United States or around the world for the treatment of cesarean scar pregnancy. There is a wide range of management options in the literature, and many of them can to lead to severe bleeding complications, which can result in loss of fertility or even maternal death. If inadequately managed, it can lead to untoward complications throughout all 3 trimesters of the pregnancy. Early detection of CSP has a paramount clinical importance.


Inhibition of hepatic Na +, K + -adenosinetriphosphatase in taurolithocholate-induced cholestasis in the rat.
Na +, K + -adenosinetriphosphatase (Na +, K + -ATPase) activity was decreased in liver plasma membranes from rats in which cholestasis had been induced by i.v. administration of sodium taurolithocholate (5 mumoles/100 g b. wt). Incubation of liver plasma membranes with taurolithocholate (10--1300 muM) caused significant and dose dependent reductions of Na +, K + -ATPase activity at taurolithocholate concentrations above 100 muM. These findings lend support to the hypothesis that cholestasis induced by monohydroxy bile acids is at least partially the result of an inhibition of hepatic Na +, K + -ATPase activity.


Corrigendum: Flurbiprofen used in one-lung ventilation improves intraoperative regional cerebral oxygen saturation and reduces the incidence of postoperative delirium.
[This corrects the article DOI: 10.3389/fpsyt.2022.889637.].


Identification of CSF biomarkers for frontotemporal dementia using SELDI-TOF.
This investigation describes the discovery of novel possible cerebrospinal fluid (CSF) biomarkers for frontotemporal dementia (FTD) using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS). Sixteen clinically diagnosed FTD patients and 12 non-demented controls were included in the study. CSF was collected and analyzed for protein expression by SELDI-TOF MS. The samples were analyzed on four different array surfaces using two different energy-absorbing molecules as matrices. In total each sample was subjected to eight different surface/matrix conditions. About 2000 protein peaks (mass/charge ratios) were detected. Forty-two peaks were differentially expressed in FTD (P < 0.01). After exclusion of peaks with low signal-to-noise ratio and/or poor resolution and peaks representing differentially charged proteins, 10 peaks remained, five of which were increased and five decreased in FTD cases compared to controls. Using partial least square discriminant analysis (PLS-DA), the combination of these biomarkers discriminated FTD from non-demented controls with a sensitivity of 94%, a specificity of 83% and an accuracy of 89%. Five of the peaks were purified further and identified by tandem MS as a fragment of neurosecretory protein VGF, transthyretin, S-cysteinylated transthyretin, truncated cystatin C and a fragment of chromogranin B. With use of these potential biomarkers, FTD can be distinguished from control subjects with high accuracy in this pilot study.


Parg deficiency confers radio-sensitization through enhanced cell death in mouse ES cells exposed to various forms of ionizing radiation.
Poly(ADP-ribose) glycohydrolase (Parg) is the main enzyme involved in poly(ADP-ribose) degradation. Here, the effects of Parg deficiency on sensitivity to low and high linear-energy-transfer (LET) radiation were investigated in mouse embryonic stem (ES) cells. Mouse Parg(-/-) and poly(ADP-ribose) polymerase-1 deficient (Parp-1(-/-)) ES cells were used and responses to low and high LET radiation were assessed by clonogenic survival and biochemical and biological analysis methods. Parg(-/-) cells were more sensitive to γ-irradiation than Parp-1(-/-) cells. Transient accumulation of poly(ADP-ribose) was enhanced in Parg(-/-) cells. Augmented levels of phosphorylated H2AX (γ-H2AX) from early phase were observed in Parg(-/-) ES cells. The induction level of p53 phophorylation at ser18 was similar in wild-type and Parp-1(-/-) cells and apoptotic cell death process was mainly observed in the both genotypes. These results suggested that the enhanced sensitivity of Parg(-/-) ES cells to γ-irradiation involved defective repair of DNA double strand breaks. The effects of Parg and Parp-1 deficiency on the ES cell response to carbon-ion irradiation (LET13 and 70 keV/μm) and Fe-ion irradiation (200 keV/μm) were also examined. Parg(-/-) cells were more sensitive to LET 70 keV/μm carbon-ion irradiation than Parp-1(-/-) cells. Enhanced apoptotic cell death also accompanied augmented levels of γ-H2AX in a biphasic manner peaked at 1 and 24h. The induction level of p53 phophorylation at ser18 was not different between wild-type and Parg(-/-) cells. The augmented level of poly(ADP-ribose) accumulation was noted after carbon-ion irradiation compared to γ-irradiation even in the wild-type cells. An enhanced poly(ADP-ribose) accumulation was further observed in Parg(-/-) cells. Both Parg(-/-) cells and Parp-1(-/-) cells did not show sensitization to Fe-ion irradiation. Parg deficiency sensitizes mouse ES cells to a wide therapeutic range of LET radiation through the effects on DNA double strand break repair responses and enhanced cell death.


Performance of Cerebrospinal Fluid Biomarkers of Alzheimer Disease in a Memory Clinic in Norway.
Although Alzheimer disease (AD) remains a clinical diagnosis, biomarkers are in use to support the diagnosis. Three cerebrospinal biomarkers, amyloid-β (Aβ), total tau (T-tau), and phospho tau (P-tau), reflect neuropathologic changes observed in AD patients. The aim of this study was to explore the performance of the cerebrospinal fluid biomarkers used in a memory clinic setting. We included 205 patients who had been through a standardized examination including lumbar puncture. Diagnoses were made blind to the results of the spinal fluid analyses. By combining low Aβ and high T-tau or P-tau values, the sensitivity was 31.9% and the specificity was 92.5% when comparing patients with AD with other patients. In receiver operating characteristic analyses, the AUC for the Aβ was 0.78 (SE=0.04; 95% CI, 0.7-0.85), for T-tau 0.80 (SE=0.03; 95% CI, 0.73-0.86), and for P-tau 0.76 (SE=0.04; 95% CI, 0.69-0.83). A significant difference was found between the sexes, with higher values of Aβ among younger men (under 65 y of age) with AD [799.8 (SD=317.2) vs. 558.9 (SD=123.5) for women, P-value=0.003]. The present study found a lower performance of the biomarkers than reported previously.


Reconstruction of a digitless hand.
A digitless left hand was reconstructed by transplanting a big toe skin-nail flap and the adjacent second and third toes taken from the left foot and the second and third toes taken from the right foot. Five months follow-up showed satisfactory functional recovery and cosmetic results. The digits have regained normal sensibility and possess independent motor ability.


Tolerance, uptake and removal of nitrobenzene by a newly-found remediation species Mirabilis jalapa L.
The growth, photosynthesis rate, and ultrastructure of Mirabilis jalapa L. as a newly-found remediation species under stress of nitrobenzene (NB) and its uptake and removal of NB by the plants were investigated. The results showed that M. jalapa plants could endure contaminated soils by lower than 10.0 mg NB kg(-1) because there was no decrease in the total length of the plant roots, the maximum length of the hypocotyle, the length of the first seminal root, the height of the shoots and the dry biomass of the seedlings as well as the photosynthesis rate of the plants compared with those in the control. In particular, the growth of the plants could be significantly (P<0.01) enhanced by 0.1 mg NB kg(-1) under unautoclaved and autoclaved soils. Ultrastructural observations on leaf cells of the plants found that these cells had smooth, clean and continuous cell membranes and cell walls, indicating that there was no obvious damage by NB in comparison with those in the control. Although the absorption of NB in shoots and roots of M. jalapa was weak, plant-promoted biodegradation of NB was considerable and the dominant contribution in the removal of NB from contaminated soils, suggesting the feasibility of M. jalapa applied to phytoremediation of NB contaminated soils.


Effects of topically potent glucocorticoids on human diploid fibroblasts in vitro.
A wide range of concentrations of both cortisol and a topically more potent synthetic derivative, fluocinolone acetonide, was found not to inhibit the growth of cultured human skin fibroblasts; fluocinolone acetonide produced a slight increase in the growth rate. Both steroids had a transient stimulatory effect on fibroblasts, promoting an earlier entry into the period DNA synthesis (S) which was also accompanied by a substantial increase in the length of S.


Mapping Aboveground Biomass of Four Typical Vegetation Types in the Poyang Lake Wetlands Based on Random Forest Modelling and Landsat Images.
Wetland biomass is an important indicator of wetland ecosystem health. In this study, four dominant vegetation communities (Carex cinerascens, Phalaris arundinacea, Artemisia selengensis, and Miscanthus sacchariflorus) in the Poyang Lake wetland from 2010 to 2016 were classified from Landsat images using spectral information divergence (SID). We combined aboveground biomass (AGB) field measurements and remote sensing data to establish a suitable model for estimating wetland AGB in Poyang Lake, which is on the Ramsar Convention's list of Wetlands of International Importance. The results showed that (1) overall, the classification accuracy for vegetation pixels across 5 years ranged from 59.1% to 73.7% and (2) the inter-annual and spatial variations in the AGB of the four vegetation types were clear. C. cinerascens had an average AGB density value of 1.28 kg m-2 in Poyang Lake from 2010 to 2016; M. sacchariflorus had the highest AGB density with an average value of 1.39 kg m-2; A. selengensis had almost the same level at 1.26 kg m-2; and P. arundinacea had the lowest AGB density at 0.64 kg m-2. This study provides useful experience for estimating carbon sequestration of vegetation in freshwater wetlands.


Likelihood ratios for glaucoma diagnosis using spectral-domain optical coherence tomography.
To present a methodology for calculating likelihood ratios for glaucoma diagnosis for continuous retinal nerve fiber layer (RNFL) thickness measurements from spectral-domain optical coherence tomography (spectral-domain OCT). Observational cohort study. A total of 262 eyes of 187 patients with glaucoma and 190 eyes of 100 control subjects were included in the study. Subjects were recruited from the Diagnostic Innovations Glaucoma Study. Eyes with preperimetric and perimetric glaucomatous damage were included in the glaucoma group. The control group was composed of healthy eyes with normal visual fields from subjects recruited from the general population. All eyes underwent RNFL imaging with Spectralis spectral-domain OCT. Likelihood ratios for glaucoma diagnosis were estimated for specific global RNFL thickness measurements using a methodology based on estimating the tangents to the receiver operating characteristic (ROC) curve. Likelihood ratios could be determined for continuous values of average RNFL thickness. Average RNFL thickness values lower than 86 μm were associated with positive likelihood ratios (ie, likelihood ratios greater than 1), whereas RNFL thickness values higher than 86 μm were associated with negative likelihood ratios (ie, likelihood ratios smaller than 1). A modified Fagan nomogram was provided to assist calculation of posttest probability of disease from the calculated likelihood ratios and pretest probability of disease. The methodology allowed calculation of likelihood ratios for specific RNFL thickness values. By avoiding arbitrary categorization of test results, it potentially allows for an improved integration of test results into diagnostic clinical decision making.


Magnetic resonance imaging of mesial temporal sclerosis: case reports.
Two patients with uncontrollable complex partial seizures had normal findings on pre- and postinfusion computed tomography scans. Magnetic resonance imaging demonstrated, in both patients, a lesion in the temporal lobe suggestive of mesial temporal sclerosis. One patient underwent temporal lobectomy, and the radiologic diagnosis was verified. In patients with complex partial seizures, magnetic resonance imaging appears to be able to noninvasively localize temporal lobe lesions in preparation for surgical intervention.


Pulmonary transvascular fluid filtration response to hypoproteinemia and Hespan infusion.
Management of major blood loss utilizing protein-free fluids for volume replacement frequently results in plasma protein depletion and plasma volume expansion. These factors can increase pulmonary transvascular fluid filtration which may lead to life-threatening pulmonary edema. We studied the combined effects of plasma protein depletion and plasma volume expansion on lung lymph flow (QL) in awake sheep prepared with chronic lung lymph fistulae. Animals were first chronically protein-depleted by batch plasmapheresis and then infused for 2 hr with either lactated Ringer's (Hypo/LR; n = 7) or 6% hydroxyethyl starch (Hespan) (Hypo/HES; n = 6). Control normoproteinemic animals (Norm/LR; n = 13) only received lactated Ringer's. Hypoproteinemia alone resulted in an average 2-fold increase in QL over normoproteinemic baseline levels (P less than or equal to 0.05). Infusion of LR into hypoproteinemic animals caused a 7.9-fold increase in QL (P less than or equal to 0.05). By comparison, HES infusion under similar hypoproteinemic conditions limited the increase in QL to 3.2-fold over baseline. We attributed this reduced rise in QL to Hespan's high oncotic pressure, which dramatically widened (by 4-5 mm Hg) the pulmonary-to-lymph oncotic pressure gradient. We did not observe this with LR infusion, or in previous studies employing intravenous infusion of plasma protein. Thus, the oncotic pressure of Hespan appears to significantly limit pulmonary fluid filtration during hypoproteinemia compared to LR. We do not believe that these effects are the results of any changes in microvascular porosity.


Challenges and Strategies to Enhance the Systemic Absorption of Inhaled Peptides and Proteins.
Proteins and peptides-based therapeutics are making substantial access to the market due to their obvious advantages of strong potency, high specificity and desirable safety profile. However, most clinical products are mainly delivered via parenteral route with inferior convenience. Lung is an attractive non-invasive alternative passage for systemic administration of biologics with numerous outstanding features, as examples of large absorptive surface area, extensive vascularization and mild local microenvironment. Even so, mucociliary clearance, alveolar macrophage phagocytosis, enzymatic metabolism, pulmonary surfactant adsorption and limited epithelium permeability constitute major obstacles affecting the systemic absorption of inhaled proteins and peptides. This article begins by giving a brief overview of challenges for the systemic absorption of inhaled proteins and peptides, and then goes on to a comprehensive review of possible strategies for enhanced pulmonary absorption, including chemical modification, addition of protease inhibitors, incorporation of absorption enhancers, modification with fusion proteins and development of particulate-based drug delivery systems. These strategies can provide enhanced transmembrane absorption capacity while avoiding pulmonary clearance, offering a valuable reference for designing pulmonary delivery systems of protein and peptide drugs.


Tocilizumab as a Therapeutic Agent for Critically Ill Patients Infected with SARS-CoV-2.
Tocilizumab is an IL-6 receptor antagonist with the ability to suppress the cytokine storm in critically ill patients infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). We evaluated patients treated with tocilizumab for a SARS-CoV-2 infection who were admitted between March 13, 2020, and April 16, 2020. This was a multicenter study with data collected by chart review both retrospectively and concurrently. Parameters evaluated included age, sex, race, use of mechanical ventilation (MV), usage of steroids and vasopressors, inflammatory markers, and comorbidities. Early dosing was defined as a tocilizumab dose administered prior to or within 1 day of intubation. Late dosing was defined as a dose administered > 1 day after intubation. In the absence of MV, the timing of the dose was related to the patient's date of admission only. We evaluated 145 patients. The average age was 58.1 years, 64% were men, 68.3% had comorbidities, and 60% received steroid therapy. Disposition of patients was 48.3% discharged and 29.3% died, of which 43.9% were African American. MV was required in 55.9%, of which 34.5% died. Avoidance of MV (P = 0.002) and increased survival (P < 0.001) was statistically associated with early dosing. Tocilizumab therapy was effective at decreasing mortality and should be instituted early in the management of critically ill patients with coronavirus disease 2019) COVID-19).


Mathematical Model of Self-Oscillations of Activity of Kai Proteins.
A non-autocatalytic mathematical model of self-oscillations in vitro in solutions of cyanobacterial Kai proteins (KaiA, KaiB, KaiC) and ATP is suggested. This model describes the process of phosphorylation/dephosphorylation of KaiC protein, which is accelerated by KaiA and inhibited by KaiB. The method of metabolic control analysis is used to show that frequency (period) as well as amplitude of self-oscillations of components of Kai proteins are temperature-compensated.


Plastic and nonplastic pyramidal cells perform unique roles in a network capable of adaptive redundancy reduction.
Pyramidal cells show marked variation in their morphology, including dendritic structure, which is correlated with physiological diversity; however, it is not known how this variation is related to a cell's role within neural networks. In this report, we describe correlations among electrosensory lateral line lobe (ELL) pyramidal cells' highly variable dendritic morphology and their ability to adaptively cancel redundant inputs via an anti-Hebbian form of synaptic plasticity. A subset of cells, those with the largest apical dendrites, are plastic, but those with the smallest dendrites are not. A model of the network's connectivity predicts that efficient redundancy reduction requires that nonplastic cells provide feedback input to those that are plastic. Anatomical results confirm the model's prediction of optimal network architecture. These results provide a demonstration of different roles for morphological/physiological variants of a single cell type within a neural network performing a well-defined function.


Artificial intelligence-assisted repurposing of lubiprostone alleviates tubulointerstitial fibrosis.
Tubulointerstitial fibrosis (TIF) is the most prominent cause which leads to chronic kidney disease (CKD) and end-stage renal failure. Despite extensive research, there have been many clinical trial failures, and there is currently no effective treatment to cure renal fibrosis. This demonstrates the necessity of more effective therapies and better preclinical models to screen potential drugs for TIF. In this study, we investigated the antifibrotic effect of the machine learning-based repurposed drug, lubiprostone, validated through an advanced proximal tubule on a chip system and in vivo UUO mice model. Lubiprostone significantly downregulated TIF biomarkers including connective tissue growth factor (CTGF), extracellular matrix deposition (Fibronectin and collagen), transforming growth factor (TGF-β) downstream signaling markers especially, Smad-2/3, matrix metalloproteinase (MMP2/9), plasminogen activator inhibitor-1 (PAI-1), EMT and JAK/STAT-3 pathway expression in the proximal tubule on a chip model and UUO model compared to the conventional 2D culture. These findings suggest that the proximal tubule on a chip model is a more physiologically relevant model for studying and identifying potential biomarkers for fibrosis compared to conventional in vitro 2D culture and alternative of an animal model. In conclusion, the high throughput Proximal tubule-on-chip system shows improved in vivo-like function and indicates the potential utility for renal fibrosis drug screening. Additionally, repurposed Lubiprostone shows an effective potency to treat TIF via inhibiting 3 major profibrotic signaling pathways such as TGFβ/Smad, JAK/STAT, and epithelial-mesenchymal transition (EMT), and restores kidney function.


[A modification of the skin reaction of the delayed type in guinea pigs].
A provocation of the delayed-type hypersensitivity in the ear of guinea pigs and the measurement of an always identical piece of skin allows a better quantification of this test. By histological studies is demonstrated that the skin thickness is the result of a characteristic infiltration with mononuclear cells 24 hours after antigen application.


Forget Forgotten Stents: Review of Ureteral Stent Tracking Systems.
Our objective was to assess existing systems for tracking ureteral stents after urological surgery and determine if these systems impact the rate of retained and forgotten stents. We performed a scoping review using the search terms ("ureteral stents" "ureteral catheters" "nephroureteral stents" "nephroureteral catheters" or "double J stents") and ("tracking" or "lost stents" or "forgotten stents"). Two of the authors individually selected relevant articles based on title and abstract and performed full review of manuscripts and references. Nine different studies focusing on forgotten ureteral stents were identified. Tracking mechanisms included electronic medical records algorithms, cellphone, chat or computer-based applications. Rates of lost or delayed removal of stents in hospitals prior to using a tracking system were 0%-13%. With a tracking mechanism, the rate of lost or delayed removal was reduced to 1% or less in the studies we identified. Stent tracking systems successfully reduced delayed removal of ureteral stents and reduced the rates of retained stents; however, these systems are institution specific, and no universal solution is readily available. Such a solution would be beneficial for the urological community to investigate further and for industry partners to invest in.


Low profile vascular plug for transarterial occlusion of patent ductus arteriosus in small dogs.
Minimally invasive transcatheter occlusion using Amplatz canine duct occluder (ACDO) is the treatment of choice for dogs with left-to-right shunting patent ductus arteriosus (PDA). However, in small dogs the femoral artery diameter is often too small to accommodate the guiding catheter required for ACDO deployment. Describe the effectiveness of transarterial implantation of Amplatzer Vascular Plug 4 (AVP-4), the only self-expandable nitinol mesh occlusion device which can be implanted through a 4 French diagnostic catheter, in small dogs with left-to-right shunting PDA. Seven client-owned dogs. Descriptive case series. Dogs with hemodynamically relevant left-to-right shunting PDA and a femoral artery diameter less than 2.0 mm measured preoperatively with ultrasonography were prospectively enrolled. Angiography after releasing the device showed complete immediate PDA closure in 5 dogs, where the manufacturers' recommendation were strictly followed (30%-50% device oversizing of the ductal ampulla's diameter). Trivial residual flow on angiography in the 6th dog, whose device was slightly undersized, had resolved on echocardiography within 2 hours after placement. Marked device undersizing in the 7th dog resulted in severe residual shunting, which necessitated the addition of a coil. In this dog, the AVP-4 embolized into the pulmonary artery within 2 weeks after placement. Transarterial implantation of AVP-4 is a safe, effective and technically easy procedure for PDA occlusion in small dogs and offers a valuable alternative to coil implantation. Accurate PDA measurement and device sizing is essential to prevent residual shunting, inadvertent device embolization, and protrusion of the device into the aorta.


Combined effects of X rays, Ro 03-8799, and hyperthermia on growth, necrosis, and cell proliferation in a mouse tumor.
A mouse adenocarcinoma was treated with 20 Gy X rays, hyperthermia (30 minutes at 43 degrees C), Ro-03-8799, or a combination of two or three of these agents. Combined treatments increase growth delay in the tumor and this was greatest with the combination of all three modalities. Extensive amounts of necrosis were observed after the combined treatments. This effect was most pronounced after treatment modalities including hyperthermia. On the other hand, the radiation-induced micronucleus formation was more enhanced by the sensitizer than by hyperthermia. After X irradiation and combined treatments with X rays a G2-block was observed in DNA-histograms. Tetraploid cells appeared in large amounts that started DNA synthesis followed by necrosis. From these tumors it was impossible to obtain regular DNA-histograms. Tumor regression is a combined result of reduced cell renewal, increased cytogenetic damage, and development of necrosis.


Role of filamentous microorganisms in activated sludge foaming: relationship of mycolata levels to foaming initiation and stability.
The relationship between the levels of mycolic acid-containing actinomycetes (mycolata), Gordonia spp. and Gordonia amarae, and foam initiation and stability was characterized using: (1) batch tests involving addition of G. amarace cells to activated sludge, (2) analysis of a full-scale activated sludge plant that experienced seasonal foaming, and (3) a study of lab-scale activated sludge reactors augmented with G. amarae. Using batch tests, threshold Gordonia levels for foam formation and foam stability were determined to be approximately 2 x 10(8) microm ml(-1) and 1 x 10(9) microm ml(-1), respectively. In the full-scale plant, the levels of Gordonia spp. and G. amarae increased during the course of foaming, and the foam formation threshold of 2 x 10 microm ml(-1) corresponded to the onset of foaming. This value was also verified in lab-scale reactor washout experiments, where decreasing mycolata levels were observed during the course of foam dissipation. The foam stability threshold of 1 x 10(9) micorm ml(-1) was verified in lab-scale reactor studies. The increase in the levels of Gordonia spp. and G. amarae in the full-scale plant corresponded to an increase in temperature, suggesting that the growth of Gordonia spp. was favored during warmer periods.


The utility of electromyography and mechanomyography for assessing neuromuscular function: a noninvasive approach.
This article introduces the utility of electromyography (EMG) and mechanomyography (MMG) for the assessment of neuromuscular function, and discusses the interpretation of the EMG and MMG signals for various exercise perturbations. The results of these studies suggest that the use of EMG and MMG to determine muscle fatigue is robust. Future studies with clinical populations are needed, however, to determine the optimal use of EMG and/or MMG for assessing muscle function in rehabilitative settings.


Clinical comparison of two suspensory fixation devices for anatomic double-bundle anterior cruciate ligament reconstruction.
The aim of this study was to compare the operation time required and the clinical outcome 2 years postoperatively, after anatomic double-bundle ACL reconstructions using hamstring tendon grafts fixed with either the EndoButton-CL-BTB(®) (ECL-BTB) or the EndoButton-CL(®) (ECL). Forty-six patients, who underwent anatomic double-bundle ACL reconstruction, were non-randomly divided into 2 groups. Patients with a combined ligament injury or complete meniscal tear were excluded from this study. In group I, an ECL was used with 23 patients. In group II, an ECL-BTB was used with the remaining 23 patients. In groups I and II, the ECL or ECL-BTB was attached to the femoral ends of the hamstring tendon autografts. In both groups, a polyester tape was connected in series with the tibial ends of the grafts. The patients were examined with standard clinical evaluations at 2 years after surgery. The operation time in group II was significantly shorter than that in group I (P = 0.0459). Concerning the intra- and postoperative complications, there were no serious complications in either group. No significant differences were found between the 2 groups in terms of knee laxity measurements, the peak muscle torque of quadriceps and hamstrings, the Lysholm score and the IKDC evaluation. This study demonstrated that the usage of the ECL-BTB for graft preparation significantly shortens the total operation time in comparison with the ECL and that there were no significant differences in the 2-year clinical outcome and the intra- and postoperative complications between the 2 graft preparation procedures of the anatomic double-bundle ACL reconstruction. The ECL-BTB can be an alternative device for the hamstring tendon graft in double-bundle ACL reconstruction. Prospective comparative cohort study, Level II.


Examination of micro-tip reversed-phase liquid chromatographic extraction of peptide pools for mass spectrometric analysis.
Mass spectrometry occupies a central position in most current protein identification schemes. So-called 'mass fingerprinting' techniques rely on composite mass patterns of proteolytic fragments, or dissociation products thereof, to query databases. Keys to successful analysis of ever smaller amounts are sensitivity and complete spectral information, both of which depend for a large part on proper sample preparation. Clean-up and concentration of peptide mixtures over eppendorf gel loading tips filled with chromatographic media (i.e. 'micro-tips') are believed to be quite useful in this regard. We have studied quantitative and qualitative aspects of polypeptide extraction using these small manual devices. Optimization of sample volume and additives, micro-tip bed volume, and eluent composition and volume, all contribute to effective recovery (approximately 65-70%, on average). Improper digest conditions can, in fact, lead to far bigger losses, suggesting the need for at least trace amounts of Zwittergent 3-16. Of particular interest is our finding that partial fractionation, obtained by two-step micro-tip elution, generally results in more and better signals during subsequent mass analysis. Thus, by using optimized micro-tips, in combination with adequate sample handling and instrumentation, direct mass spectrometric identification can be routinely and successfully done in any resource facility type setting.


Identification of putative crustacean neuropeptides using in silico analyses of publicly accessible expressed sequence tags.
The development of expressed sequence tags (ESTs) for crustacean cDNA libraries and their deposition in publicly accessible databases has generated a rich resource for peptide discovery in this commercially and ecologically important arthropod subphylum. Here, we have conducted in silico searches of these databases for unannotated ESTs encoding putative neuropeptide precursors using the BLAST program tblastn, and have predicted the mature forms of the peptides encoded by them. The primary strategy used was to query the database with known decapod prepro-hormone sequences or, in some instances, insect precursor protein sequences. For neuropeptides for which no prepro-hormones are known, the peptides themselves were used as queries. For those peptides expected to originate from a common precursor, the individual sequences were combined, with each peptide flanked by a dibasic processing site and, if amidated, a glycine residue. Using these approaches, 13 unannotated ESTs encoding putative neuropeptide precursors were found. For example, using the first strategy, putative Marsupenaeus japonicus prepro-hormones encoding B-type allatostatins, neuropeptide F (NPF), and orcokinins were identified. Similarly, several Homarus americanus ESTs encoding putative orcokinin precursors were found. In addition to the decapod prepro-hormones, ESTs putatively encoding a NPF isoform and a red pigment concentrating hormone-like peptide were identified from the cladoceran Daphnia magna, as was one EST putatively encoding multiple tachykinin-related peptides from the isopod Eurydice pulchra. Using the second strategy, we identified a Carcinus maenas EST encoding HIGSLYRamide, a peptide recently discovered via mass spectrometry from Cancer productus. Using mass spectral methods we confirmed that this peptide is also present in Carcinus maenas. Collectively over 50 novel crustacean peptides were predicted from the identified ESTs, providing a strong foundation for future investigations of the evolution, regulation and function of these and related molecules in this arthropod taxon.


Enzymatic hydrolysis optimization to ethanol production by simultaneous saccharification and fermentation.
There is tremendous interest in using agro-industrial wastes, such as cellulignin, as starting materials for the production of fuels and chemicals. Cellulignin are the solids, which result from the acid hydrolysis of the sugarcane bagasse. The objective of this work was to optimize the enzymatic hydrolysis of the cellulose fraction of cellulignin, and to study its fermentation to ethanol using Saccharomyces cerevisiae. Cellulose conversion was optimized using response surface methods with pH, enzyme loading, solid percentage, and temperature as factor variables. The optimum conditions that maximized the conversion of cellulose to glucose, calculated from the initial dried weight of pretreated cellulignin, (43 degrees C, 2%, and 24.4 FPU/g of pretreated cellulignin) such as the glucose concentration (47 degrees C, 10%, and 25.6 FPU/g of pretreated cellulignin) were found. The desirability function was used to find conditions that optimize both, conversion to glucose and glucose concentration (47 degrees C, 10%, and 25.9 FPU/g of pretreated cellulignin). The resulting enzymatic hydrolyzate was fermented yielding a final ethanol concentration of 30.0 g/L, in only 10 h, and reaching a volumetric productivity of 3.0 g/L x h, which is close to the values obtained in the conventional ethanol fermentation of sugar cane juice (5.0-8.0 g/L x h) in Brazil.


Association of beta-thalassemia and Hb Q-Thailand resulting in a normal Hb A2 value.
We describe a Chinese woman who was assumed to be a Hb Q-Thailand heterozygote, but was later also shown to have beta-thalassemia (beta-thal) with a normal amount of Hb A(2).


Binocular vision and abnormal head posture in children when watching television.
To determine the association between the binocular vision and an abnormal head posture (AHP) when watching television (TV) in children 7-14y of age. Fifty normal children in the normal group and 52 children with an AHP when watching TV in the AHP group were tested for spherical equivalents, far and near fusional convergence (FC) and fusional divergence (FD) amplitudes, near point of convergence, far and near heterophoria, accommodative convergence/ accommodation ratio and stereoacuity. The values of these tests were compared between the two groups. The independent t test was applied at a confidence level of 95%. The far and near FC amplitudes and far FD amplitudes were lower in the AHP group (the far FC amplitudes: break point 13.6±5.4(Δ), recovery point 8.7±5.4(Δ). The near FC amplitudes: break point 14.5±7.3(Δ), recovery point 10.3±5.1(Δ). The far FD amplitudes: break point 3.9±2.7(Δ), recovery point 2.6±2.3(Δ)) compared with those in the normal group (the far FC amplitudes: break point 19.1±6.2(Δ), recovery point 12.4±4.5(Δ). The near FC amplitudes: break point 22.3±8.0(Δ), recovery point 16.1±5.7(Δ). The far FD amplitudes: break point 7.0±2.1(Δ), recovery point 4.6±1.9(Δ)). Other tests presented no statistically significant differences. An association between the reduced FC and FD amplitudes and the AHP in children when watching TV is proposed in the study. This kind of AHP is considered to be an anomalous manifestation which appears in a part of puerile patients of fusional vergence dysfunction.


Lack of impact of early antibiotic therapy for streptococcal pharyngitis on recurrence rates.
To determine whether recurrence rates for group A beta-hemolytic streptococcal (GABHS) pharyngitis are related to the time of initiation of antibiotic therapy, we randomly assigned 113 patients with GABHS pharyngitis either to a group that began a 10-day course of penicillin V at the time of diagnosis or to a group that began the same antibiotic regimen after a dealy of 48 hours. Follow-up throat culture specimens were obtained 4 days, 2 months, and 4 months after the completion of antibiotic therapy, as well as during any interim episodes of acute pharyngitis. Serotyping of all GABHS isolates was performed to distinguish between recurrences with homologous serotypes and new acquisitions with heterologous serotypes. There was no significant difference between the two treatment groups in age, gender, duration of illness before enrollment in the study, initial clinical presentation, or compliance. Of the 50 patients in the immediate-treatment group, 6 (12%) had homologous serotypes of GABHS isolated on one of the follow-up throat cultures. Of the 63 patients in the delayed-treatment group, 9 (14%) had homologous serotypes of GABHS isolated on one of the follow-up throat cultures. These data indicate that a 48-hour delay in the initiation of penicillin therapy for GABHS pharyngitis does not reduce the recurrence rate.


Pretreatment Microvessel Density for Predicting of Tumor Responsiveness to Neoadjuvant Chemoradiotherapy of Locally Advanced Rectal Cancer.
This study aimed to assess whether pretreatment tumor tissue microvessel density (MVD) could be a potential predictive marker for Mandard response in LARC treated with nCRT. A retrospective analysis was performed in pretreatment paraffin-embedded specimens of 31 pathologically confirmed rectal adenocarcinoma. All patients received nCRT and subsequent total mesorectal resection. Tumor MVD was determined by an average number of counted CD34-stained endothelial cells from two selected fields at 200x magnification in each slide and categorized into two groups: low MVD (</=60) and high MVD (> 60). The tumor response was determined using the Mandard tumor regression grading system. The subjects were grouped according to their TRG into responder (TRG 1-3) and non-responder (TRG 4-5). Twenty out of thirty-one patients (64.5%) were defined as responders. Eleven patients (35.5%) were defined as non-responders. MVD was significantly associated with tumor responsiveness to nCRT (p < 0.05). High MVD was shown to be an independent risk factor associated with tumor resistance to nCRT (OR, 22.58; 95% CI, 1.943-262.34; p = 0.013). A strong correlation was found between MVD and TRG (correlation coefficient value of 0.642, p <0.01), between MVD and vascular invasion (correlation coefficient value of 0.618, p <0.01), and between nodal involvement and vascular invasion (correlation coefficient value of 0.521, p <0.01). A moderate correlation was found between nodal involvement and vascular invasion (correlation coefficient value of 0.406, p <0.05). High MVD in pretreatment tumor tissue was significantly associated with the tumor resistance to nCRT.