Utilization of N,S-doped carbon dots as a fluorescent nanosensor for determination of cromolyn based on inner filter effect: application to aqueous humour.
A simple and eco-friendly hydrothermal technique is used to prepare water soluble N- and S-co-doped carbon quantum dots probes (N,S-CQDs) from thiosemicarbazide and citric acid. Several characterization techniques were performed to ensure the successful synthesis of highly luminescent N,S-CQDs. The prepared probe exhibited analytical potential as an optical nanosensor for the spectrofluorimetric determination of cromolyn sodium (CRO) in its pharmaceutical dosage forms and aqueous humour. The emission intensity of the synthesized N,S-CQDs was measured at 411 nm after excitation at 345 nm. Addition of increasing concentrations of CRO to N,S-CQDs led to quenching of its fluorescence intensity. CRO was investigated within a wide concentration range 10.0-150.0 μM with a limit of detection of 2.0 μM and a limit of quantification of 6.0 μM. The quenching of fluorescent N,S-CQDs occurred through the inner filter effect (IFE). The developed spectrofluorimetric method was successfully optimized and validated according to the International Council of Harmonisation guidelines (ICH). The method greenness is proved through using both Eco-Scale and AGREE approaches.


Non-N-methyl-D-aspartate receptors may mediate the transmission of emetic signals between visceral vagal afferents and the solitary nucleus in dogs.
The effects of the N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists MK-801 and NBQX, respectively, on salivary secretion and retching induced by vagal stimulation were studied in decerebrate dogs. Vagal stimulation induced an increase in salivary secretion and fictive retching. Intra-4th ventricular application of vehicle or MK-801 did not change either response, while NBQX completely abolished both responses. These results suggest that non-NMDA receptors mediate both responses in the solitary nucleus.


Do behavioral pharmacology findings predict clinical trial outcomes? A proof-of-concept in medication development for alcohol use disorder.
Behavioral pharmacology paradigms have been used for early efficacy testing of novel compounds for alcohol use disorder (AUD). However, the degree to which early efficacy in the human laboratory predicts clinical efficacy remains unclear. To address this gap in the literature we employed a novel meta-analytic approach. We searched the literature for medications tested for AUD using both behavioral pharmacology (i.e., alcohol administration) and randomized clinical trials (RCTs). For behavioral pharmacology, we computed medication effects on alcohol-induced stimulation, sedation, and craving during the alcohol administration (k = 51 studies, 24 medications). For RCTs, we computed medication effects on any drinking and heavy drinking (k = 118 studies, 17 medications). We used medication as the unit of analysis and applied the Williamson-York bivariate weighted least squares estimation to preserve the errors in both the independent and dependent variables. Results, with correction for publication bias, revealed a significant and positive relationship between medication effects on alcohol-induced stimulation (β = 1.18 p < 0.05), sedation (β = 2.38, p < 0.05), and craving (β = 3.28, p < 0.001) in the laboratory, and drinking outcomes in RCTs, such that medications that reduced stimulation, sedation, and craving during the alcohol administration were associated with better clinical outcomes. A leave-one-out Monte Carlo analysis examined the predictive utility of these laboratory endpoints for each medication. The observed clinical effect size was within one standard deviation of the mean predicted effect size for all but three pharmacotherapies. This proof-of-concept study demonstrates that behavioral pharmacology endpoints of alcohol-induced stimulation, sedation, and craving track medication effects from the human laboratory to clinical trial outcomes. These results apply to alcohol administration phenotypes and may be especially useful to medications for which the mechanisms of action involve alterations in subjective responses to alcohol (e.g., antagonist medication). These methods and results can be applied to a host of clinical questions and can streamline the process of screening novel compounds for AUD. For instance, this approach can be used to quantify the predictive utility of cue-reactivity screening models and even preclinical models of medication development.


Evaluation of a two-dimensional diode array for patient-specific quality assurance of HyperArc.
To evaluate a two-dimensional diode array for patient-specific quality assurance of VMAT stereotactic radiosurgery (SRS) plans. The diode array, an SRS MapCHECK (SRSMC), was composed of a 77 mm ×77 mm face-centered array having a spacing of 2.47 mm. Sixty SRS plans were selected from our clinical database, 30 for treatment of a single target and 30 for multiple targets. The target sizes ranged from 2.4 mm to 44.7 mm equivalent diameter (median 8.7 mm). The plans were delivered to the diode array. For multiple target plans, two measurements were obtained at two locations, one corresponding to the largest target and the other to the smallest target. Gamma using a 3%/1 mm criteria and the dose to the center diode were compared with radiochromic film (RCF). Dose to selected regions of the detector electronics was calculated. The mean difference between the center diode and RCF was -1.2%. For a threshold of at least 95% of detectors/pixels having gamma < 1 for a 3%/1 mm criteria, SRSMC and RCF gave consistent results for 79 of the 90 measurements. For plans with an arc having a patient support angle of 90° or 270°, the median dose to the electronics was 0.65% of the prescription dose. SRSMC is an efficient tool for accurate patient-specific quality assurance of VMAT single and multiple target radiosurgery, yielding similar clinical decisions as radiochromic film.


Differential effects of α-tocopherol and N-acetyl-cysteine on advanced glycation end product-induced oxidative damage and neurite degeneration in SH-SY5Y cells.
Advanced glycation end products (AGEs) result from non-enzymatic glycation of proteins and cause cellular oxidative stress in a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent manner. Due to these effects, AGEs are implicated as a causal factor in diabetic complications. Several antioxidants, including vitamin E, improve cell viability and diminish markers of oxidative damage in cells exposed to AGEs. However, vitamin E has been studied in cell culture systems with primary focus on apoptosis and lipid peroxidation, while its influences on AGE-induced protein and DNA oxidation, intracellular antioxidant status and cell morphology remain largely unknown. Here, we verify the suppression of AGE-induced cell death and lipid peroxidation by 200μM α-tocopherol in SH-SY5Y cells. We report the partial inhibition of DNA oxidation and a decrease in protein carbonyl formation by α-tocopherol with no effects on intracellular GSH concentrations. We observed that 2mM N-acetyl cysteine (NAC) also had a suppressive effect on DNA and protein oxidation, but unlike α-tocopherol, it caused a marked increase in intracellular GSH. Finally, we compared the ability of both antioxidants to maintain neurites in SH-SY5Y cells and found that α-tocopherol had no effect on neurite loss due to AGEs, while NAC fully maintained cell morphology. Thus, while α-tocopherol suppressed AGE-induced macromolecule damage, it was ineffective against neurite degeneration. These results may implicate thiol oxidation and maintenance as a major regulator of neurite degeneration in this model.


Are children with asthma overconfident that they are using their inhalers correctly?
The objectives of this study were to quantify the extent to which children with asthma are overconfident that they are using their inhalers correctly and determine whether demographic and clinical characteristics are associated with children being overconfident. Children (n = 91) ages 7-17 with persistent asthma were recruited at two pediatric practices in North Carolina and demonstrated their inhaler technique for metered dose inhalers during an office visit. Children were dichotomized into two groups based on how confident they were that they were using their inhalers correctly: "completely confident" or "not completely confident". The mean number of inhaler steps (out of 8) children performed incorrectly was examined. We applied linear regression models for children in the "completely confident" group to determine whether demographic and clinical factors predicted their overconfidence, defined as the number of inhaler steps performed incorrectly. Children were primarily male (56%) and non-Hispanic White (60%). Sixty-eight (75%) children were "completely confident" that they were using their inhalers correctly. The "completely confident" group missed an average of 1.5 steps. In the "completely confident" group, males (p < 0.04) missed significantly more steps than females. The two most common errors were forgetting to shake the inhaler and holding their breath for 10 s. Regardless of their confidence level, children in our sample missed an average of 1-2 steps on an inhaler technique assessment. Findings from this study provide new evidence that it is insufficient to ask children if they are using their inhalers correctly. Therefore, it is vital that providers ask children to demonstrate their inhaler technique during health encounters.


Rates of Reconstruction Failure in Patients Undergoing Immediate Reconstruction With Tissue Expanders and/or Implants and Postmastectomy Radiation Therapy.
Mastectomy rates for breast cancer have increased, with a parallel increase in immediate reconstruction. For some women, tissue expander and implant (TE/I) reconstruction is the preferred or sole option. This retrospective study examined the rate of TE/I reconstruction failure (ie, removal of the TE or I with the inability to replace it resulting in no final reconstruction or autologous tissue reconstruction) in patients receiving postmastectomy radiation therapy (PMRT). Between 2004 and 2012, 99 women had skin-sparing mastectomies (SSM) or total nipple/areolar skin-sparing mastectomies (TSSM) with immediate TE/I reconstruction and PMRT for pathologic stage II to III breast cancer. Ninety-seven percent had chemotherapy (doxorubicin and taxane-based), 22% underwent targeted therapies, and 78% had endocrine therapy. Radiation consisted of 5000 cGy given in 180 to 200 cGy to the reconstructed breast with or without treatment to the supraclavicular nodes. Median follow-up was 3.8 years. Total TE/I failure was 18% (12% without final reconstruction, 6% converted to autologous reconstruction). In univariate analysis, the strongest predictor of reconstruction failure (RF) was absence of total TE/I coverage (acellular dermal matrix and/or serratus muscle) at the time of radiation. RF occurred in 32.5% of patients without total coverage compared to 9% with coverage (P=.0069). For women with total coverage, the location of the mastectomy scar in the inframammary fold region was associated with higher RF (19% vs 0%, P=.0189). In multivariate analysis, weight was a significant factor for RF, with lower weight associated with a higher RF. Weight appeared to be a surrogate for the interaction of total coverage, thin skin flaps, interval to exchange, and location of the mastectomy scar. RFs in patients receiving PMRT were lowered with total TE/I coverage at the time of radiation by avoiding inframammary fold incisions and with a preferred interval of 6 months to exchange.


Diabetic ketoacidosis at diagnosis in Austrian children: a population-based analysis, 1989-2011.
To analyze the effect of a community-based, poster-focused prevention program on the frequency of diabetic ketoacidosis (DKA) at diabetes onset in Austria. All newly diagnosed patients with diabetes ≤ 15 years of age were registered prospectively by the Austrian Diabetes Incidence Study Group. Registered data included initial blood glucose, pH, and ketonuria. DKA was defined as pH < 7.3 and severe DKA as pH < 7.1. Data between 1989 and 2011 were available. In autumn, 2009, a community-based prevention program similar to the Parma Campaign, in which posters were dispensed broadly, was initiated. The frequency of DKA at the onset of diabetes in the years 2005-2009 and 2010-2011 was compared. During the study period, 4038 children were registered. A total of 37.2% presented with DKA; 26% had a mild and 11.2% a severe form. The frequency of DKA was negatively associated with age at onset. In the years before the intervention program, 26% had mild DKA compared with 27% after the intervention (not significant). The prevalence of severe DKA in the years before the campaign was 12% compared with 9.5% thereafter (not significant). No significant change in the DKA rate at onset by the prevention program could be found when we compared age groups <5, 5 to <10, and 10 to <15 years, neither for mild nor for severe DKA. The frequency of DKA in children with newly diagnosed type 1 diabetes in Austria is high and did not change despite the efforts of a community-based information program.


Heavy metals bioaccumulation and histopathological changes in Auchenoglanis occidentalis fish from Tiga dam, Nigeria.
The assessment of heavy metals concentration in Tiga dam, Nigeria vis-à-vis their bioaccumulation and histopathological alterations in Auchenoglanis occidentalis from it were carried out. The water of the dam and the liver of the fish were analyzed for zinc (Zn), cadmium (Cd), lead (Pb) and iron (Fe) concentrations and their bioaccumulation factors. At the same time, the gills, liver and kidney of the exposed fish were also examined for histopathological alterations. The results revealed that concentrations of the metals differs significantly (p < 0.05) between the dam's water and the liver of the sampled fish. Liver bioaccumulations of the metals were in the order of Zn > Fe > Cd > Pb. However, the degree of tissue alterations in the gills showed their normal functioning despite the observed alterations while liver and kidney were mildly and moderately damaged, respectively. This indicated that Zn, Cd, Pb and Fe polluted the dam.


The clinical significance of pathological findings in surgically resected margins of the primary tumor in head and neck carcinoma.
Two hundred seventy (270) consecutive surgical patients treated at Roswell Park Memorial Institute for carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx between 1977 and 1982 were reviewed to determine the relationship between pathological findings at the surgical margins of the primary tumor and the incidence of local recurrence and clinical outcome. The estimated 5-year disease-free survival rate was 39% for patients with free surgical margins (10%--hypopharynx, 30%--oropharynx, 40%--oral cavity, and 53%--larynx) and 7% for not-free surgical margins. Patients with free surgical margins and with well-differentiated squamous cell carcinoma had better prognosis than those patients with moderately- and poorly-differentiated carcinomas. The local recurrence rate for Stage T1 and T2 lesions with free surgical margins was 17%, compared with 27% for Stages T3 and T4. The results of this study indicate that pathological evidence of complete excision of the primary tumor is important and attempts should be made to obtain pathological clearance. The local recurrence rate for Stage T3 and T4 lesions is high. Adjuvant therapy is indicated and post-operative radiotherapy is recommended.


Endometrial cancer in young, normal-weight women.
To determine if young, normal-weight women with endometrial cancer have unique risk factors and clinical characteristics when compared with young, overweight and obese women with endometrial cancer. Between 1989 and 2003, 1531 patients were treated for endometrial cancer. 188 (12%) of these women were premenopausal and under the age of 50 at time of diagnosis. The patients were divided into three groups based on body mass index (BMI): normal weight (BMI < 25 kg/m2), overweight (BMI 25-30 kg/m2) and obese (BMI > or = 30 kg/m2). Clinical and pathologic characteristics were compared. Of the 188 young endometrial cancer patients, 47 (25%) were of normal weight, 31 (17%) overweight and 106 (56%) obese. 4% of normal-weight, 12% of overweight and 0% of obese patients met criteria for Lynch syndrome/hereditary non-polyposis colorectal cancer (HNPCC). Irregular menstrual cycles were reported by 30% normal-weight, 32% of overweight and 61% of obese women (P = 0.001). 17% of normal-weight, 7% of overweight and 14% of obese women had a history of infertility (P = 0.723). Nulliparity was noted in 57% of normal-weight, 47% of overweight and 57% of obese patients (P = 0.583). Diabetes was reported in 4% of normal-weight, 13% of overweight and 35% of obese patients (P < 0.001). 28% of normal-weight, 26% of overweight and 14% of obese patients had synchronous primary tumors of the endometrium and ovary. As expected, a significantly higher proportion of obese and overweight women had diabetes and irregular menstrual cycles. Among the normal-weight women, a high proportion were nulliparous, had a history of infertility, irregular menstrual cycles and synchronous tumors of the endometrium and ovary when compared with the general population. This suggests that hormonal factors, and possibly polycystic ovarian syndrome (PCOS), may contribute to the development of endometrial cancer in young normal-weight women.


Interactions between migraine and tension-type headache and alcohol drinking, alcohol flushing, and hangover in Japanese.
The aim of the study was to investigate associations between headache types and alcohol drinking, alcohol flushing, and hangover. Alcohol consumption is inhibited by the presence of inactive aldehyde dehydrogenase-2 (ALDH2) whose carriers are susceptible to alcohol flushing and hangovers. We conducted a cross-sectional study of the 2,577 subjects (men/women: 1,018/1,559) who reported having ever experienced headaches unrelated to common colds and alcohol hangovers among 5,408 (2,778/2,630) Tokyo health checkup examinees. We used a questionnaire inquiring about current and past facial flushing after drinking a glass of beer which identifies the presence of inactive ALDH2 with a sensitivity and specificity of approximately 90%. Based on ICHD-II criteria migraine was diagnosed in 419 (75/344) subjects, and tension-type headache (TTH) in 613 (249/364). We classified the headaches of the remaining 1,545 (694/851) of headaches sufferers into the category "other headaches (OH)". The migraineurs drank alcohol less frequently than the subjects with TTH among current/past alcohol flushers and than the subjects with OH regardless of flushing category. No such difference in drinking frequency was observed between TTH and OH. Current/past flushers drank alcohol less frequently than never flushers, and the likelihood that male migraineurs would avoid alcohol drinking than men with TTH or OH was stronger among current/past flushers than among never flushers. Flushers and women were more susceptible to hangover than never flushers and men, respectively, regardless of headache type. Among never flushers, women with migraine were more susceptible to hangover than women with OH. The difference in alcohol sensitivity may partly explain less alcohol consumption by migraineurs.


Metabolic profiling of potential lung cancer biomarkers using bronchoalveolar lavage fluid and the integrated direct infusion/ gas chromatography mass spectrometry platform.
Lung cancer is one of the ten most common causes of death worldwide, so that the search for early diagnosis biomarkers is a very challenging task. Bronchoalveolar lavage fluid (BALF) provides information on cellular and biochemical epithelial surface of the lower respiratory tract constituents and no previous metabolomic studies have been performed with BALF samples from patients with lung cancer. Therefore, this fluid has been explored looking for new contributions in lung cancer metabolism. In this way, two complementary metabolomics techniques based on direct infusion high resolution mass spectrometry (DI-ESI-QTOF-MS) and gas chromatography mass spectrometry (GC-MS) have been applied to compare statistically differences between lung cancer (LC) and control (C) BALF samples, using partial least square discriminant analysis (PLS-DA) in order to find and identify potential biomarkers of the disease. A total of 42 altered metabolites were found in BALF from LC. The metabolic pathway analysis showed that glutamate and glutamine metabolism pathway was mainly altered by this disease. In addition, we assessed the biomarker specificity and sensitivity according to the area under the receiver operator characteristic (ROC) curves, indicating that glycerol and phosphoric acid were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. The search for early diagnosis of lung cancer is a very challenging task because of the high mortality associated to this disease and its critical linkage to the initiation of treatment. Bronchoalveolar lavage fluid provides information on cellular and biochemical epithelial surface of the lower respiratory tract constituents and no previous metabolomic studies have been performed with BALF samples from patients with lung cancer. Since BALF is in close interaction with lung tissue it is a more representative sample of lung status than other peripheral biofluids as blood or urine studied in previous works. Therefore, this study represents an innovative contribution in this topic that complement previous investigations about lung cancer, opening up new possibilities for understanding the pathogenesis of this disease and the use of efficient biomarkers. Therefore, this fluid has been explored looking for new contributions in lung cancer metabolism. In this way, two complementary metabolomic techniques based on direct infusion high resolution mass spectrometry (DI-ESI-QTOF-MS) and gas chromatography mass spectrometry (GC-MS) have been applied to compare statistically significant differences between lung cancer (LC) and control (C) BALF samples, using partial least square discriminant analysis (PLS-DA) in order to find and identify potential biomarkers of the disease. A total of 42 altered metabolites were found in BALF from LC. The metabolic pathway analysis showed that glutamate and glutamine metabolism pathway was mainly altered by this disease. In addition, we assessed the biomarker specificity and sensitivity according to the area under the receiver operator characteristic (ROC) curves, indicating that glycerol and phosphoric acid were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis.


Equine Pulmonary Agenesis and Hypoplasia Associated With Diaphragmatic Herniation.
Pulmonary malformations are rare equine congenital anomalies. Over a 3-year timeframe, three cases of left sided pulmonary agenesis were diagnosed in perinatal foals. All three cases were associated with concurrent ipsilateral diaphragmatic herniation and hypoplasia of the right lung lobe. All three foals died immediately following parturition due to perinatal asphyxia associated with the congenital malformations. To the author's knowledge, this is the first report of pulmonary agenesis in the horse.


Incidental Detection of Ilium Langerhans Cell Histiocytosis on 99m Tc-DTPA Renal Dynamic Scintigraphy.
We report the case of a 24-year-old man who underwent 99m Tc-DTPA scintigraphy for the evaluation the renal function. This scan incidentally showed an abnormal uptake of 99m Tc-DTPA in the left lower abdominal region. SPECT/CT fusion images showed osteolytic bone destruction in the left ilium associated with soft tissue mass and elevated DTPA uptake. Biopsy pathology of the ilium lesion demonstrated Langerhans cell histiocytosis.


Effect and mechanism of cyclodextrins on nitrate reduction and bio-activity by S.oneidensis.MR-1.
Cyclodextrins (CDs) have been widely used due to the excellent solubilization of hydrophobic organics. However, their effect on the biotransformation process of hydrophilic pollutants is unclear. This study first evaluated the effect and mechanism of CDs on nitrate reduction by S.oneidensis.MR-1. The three CDs (α-CD, β-CD and γ-CD) all accelerated nitrate reduction, among which β-CD had the best effect. The nitrate reduction rate was increased by 21.8% with 0.5 mM β-CD. As for the mechanism, β-CD increased the biomass, membrane permeability and EPS of S.oneidensis.MR-1. The nitrate reductase activity was also increased by 1.34-fold with 0.5 mM β-CD. The current exchange density and the electron transfer system activity were increased by 11.4% and 99.5% in the β-CD-supply system, respectively. It confirmed that β-CD enhanced the biological and electrochemical characteristics and then enhanced bio-activity. This study provides a new understanding of CDs in microbial remediation and broadens the practical application.


Risk for elevated blood lead levels in 3- and 4-year-old children.
We conducted a study to evaluate the relation between environmental, demographic, and medical risk factors and late-onset childhood lead poisoning, defined as children who were poisoned at age 3 or older. We performed a retrospective case-control study of 262 children whose test results showed non-elevated (<10 microg/dl) blood lead levels (BLLs) before age 2 but levels > or =10 microg/dl after age 3 and of 300 control children who had non-elevated BLL test results before age 2 and also after age 3. The target population was children receiving care at MetroHealth Medical Center in Cleveland, OH. We modeled the association between demographic and clinical risk factors and BLLs > or =10 microg/dl after age 3. Covariates considered were race, gender, body mass index, immunization status, mean corpuscular volume, hematocrit, red cell volume distribution width (RDW), red blood count, hemoglobin, baseline BLL result, and time between the baseline and second BLL test. Case children were more likely to be male (P < 0.0001), black (P = 0.0189) and to have a high RDW defined as > or =14.5 % (P = 0.0083). On the basis of the final model, children with BLLs 7-9 microg/dl before age 2 and again after a follow-up BLL test (<21 months) were more likely to become lead poisoned than were control children. The risk of black children developing lead poisoning increased over time, regardless of the child's first BLL test result. Although national recommendations are to test children's blood lead levels at ages 1 and 2, children living in high-risk areas with such risk factors should have a blood lead test at these older ages.


Adrenal function in cystic fibrosis.
Cystic fibrosis (CF) is not known to directly affect the adrenal gland, but commonly used CF therapies do impact the function of the hypothalamic-pituitary-adrenal (HPA) axis. By binding to the glucocorticoid receptor, medications such as inhaled and oral corticosteroids can enhance the systemic effects of cortisol and result in iatrogenic Cushing syndrome. Prolonged use suppresses the body's ability to make cortisol, resulting in iatrogenic adrenal insufficiency upon medication discontinuation. Chronic use of inhaled and oral corticosteroids can negatively affect bone health, growth, and glucose metabolism. This chapter provides practical guidelines regarding the screening, diagnosis, and treatment of iatrogenic adrenal insufficiency. As the guidelines are mainly derived from the asthma literature, this chapter also highlights the need for studies to evaluate the impact of CF therapies on adrenal function and other CF-endocrinopathies.


[Stimulating effect of long-term small-dose radiation on lymphopoiesis in mammals].
Mathematical models of lymphopoietic variations in mammals exposed to acute and chronic irradiation have been developed. They are based on the cheilone theory of hemopoiesis regulation. The models are systems of 9 nonlinear differential equations. They give a qualitative and quantitative description of lymphocytes in peripheral blood and their precursors in bone marrow of irradiated mammals. These models have for the first time simulated the stimulating effect of prolonged irradiation with small dose rates on recovery processes in the lymphopoietic system.


Infections and antibiotic prophylaxis in reconstructive vascular surgery.
In 98 patients undergoing elective vascular surgery, specimens for bacterial cultures were obtained from urine, ischaemic ulcers, incisional wounds and the implanted grafts. Wound and graft infections were registered and compared with the results of these cultures and suspected risk factors in an attempt to find the source of infections. Antibiotic prophylaxis with cefuroxime was given for 24 h beginning at the start of surgery. Patients with ischaemic ulcers also received "spread prophylaxis", directed against isolated bacteria, for ten days. Three cases of graft infection and twelve cases of wound infection occurred. Positive postoperative cultures from wounds did not correlate with pre- or peroperative cultures. Peroperative cultures revealed small numbers of staphylococcus epidermidis in eleven patients, and none of them developed graft infection. Ischaemic ulcers, diabetes or re-do procedures were not accompanied by a significantly increased frequency of wound or graft infection, although each of three patients with graft infection had one of these risk factors. Bacteria, sensitive to cefuroxime, were found in one graft infection, six wound infections, and in two patients with urosepsis, whereas cefuroxime resistant organisms were isolated from one graft infection and three infected wounds. One of the three graft infections was probably caused by bacteria originating from the patient's ischaemic ulcer. In the other two patients the source of bacteria could not be determined. Cefuroxime seems to be an adequate alternative for prophylaxis of vascular graft infection, but in some patients with bacteriuria or indwelling catheters, a one day regimen may be too short.


Impact of the CATIE trial on antipsychotic prescribing patterns at a state psychiatric facility.
Results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) indicate that, with the exception of olanzapine, no substantial overall differences were identified between second generation antipsychotics (SGAs) and the first generation antipsychotic (FGA) perphenazine. This study evaluated the effect of CATIE on antipsychotic prescribing. A retrospective review of 1807 adults with schizophrenia was conducted and relative quarterly percentages of FGA versus SGA prescriptions were calculated. Time series analysis did not identify significant differences in rates of FGA prescriptions. Critiques of the methods used in CATIE may have mitigated its potential impact on antipsychotic prescribing despite cost-effectiveness of perphenazine treatment.


Ecological risks induced by consumption and emission of Pharmaceutical and personal care products in Qinghai-Tibet Plateau: Insights from the polar regions.
As the third pole of the world and Asia's water tower, the Tibetan Plateau experiences daily release of pharmaceutical and personal care products (PPCPs) due to increasing human activity. This study aimed to explore the potential relationship between the concentration and composition of PPCPs and human activity, by assessing the occurrence of PPCPs in areas of typical human activity on the Qinghai-Tibet Plateau and evaluating their ecological risk. The results indicate that 28 out of 30 substances were detected in concentrations ranging from less than 1 ng/L to hundreds of ng/L, with the average concentration of most PPCPs in the Tibet Autonomous Region being higher than that in Qinghai Province. Among the detected substances, CAF, NOR, CTC, CIP, TCN, OTC, AZN, and DOX accounted for over 90% of the total concentration. The emission sources of PPCPs were identified by analyzing the correlation coefficients of soil and water samples, with excess PPCPs used by livestock breeding discharged directly into soil and then into surface water through leaching or runoff. By comparing the concentration and composition of PPCPs with those in other regions, this study found that CIP, ENR, LOM, NOR, CTC, DOX, OTC, and TCN were the most commonly used PPCPs in the Qinghai-Tibet Plateau. To assess the ecological risk of PPCPs, organisms at different trophic levels, including algae, crustaceans, fish, and insects, were selected. The prediction of the no effect concentration of each PPCP showed that NOR, CTC, TCN, CAF, and CBZ may have deleterious effects on water biota. This study can assist in identifying the emission characteristics of PPCPs from different types and intensities of human activities, as well as their occurrence and fate during the natural decay of aquatic systems.


Protein kinase A modulates an endogenous calcium channel, but not the calcium-activated chloride channel, in Xenopus oocytes.
In Xenopus oocytes, Ca2+ influx through an endogenous voltage-gated Ca2+ channel activates a transient outward Cl- current (ICl(Ca)), which is potentiated by cAMP increase. The site of cAMP effect appears to be the Ca2+ channel instead of the Ca(2+)-activated Cl- channel, because cAMP potentiates the Ba2+ current through the Ca2+ channel in a similar way to the ICl(Ca), and cAMP does not potentiate the Ca(2+)-dependent Cl- current in cells treated with Ca2+ ionophore. Using the catalytic subunit of protein kinase A (PKA) and PKA inhibitors, it was shown that PKA is both necessary and sufficient for the cAMP effect on ICl(Ca). Furthermore, the cAMP/PKA-mediated potentiation of ICl(Ca) was inhibited by both type 1 and type 2A protein phosphatases.


Impact of Sarcopenic Obesity on Long-Term Cancer Outcomes and Postoperative Complications After Gastrectomy for Gastric Cancer.
The prevalence of sarcopenia in gastric cancer (GC), although varying among the reported studies, is around 60%. In the last few years, it has been recognised that sarcopenia can also occur not only in patients with weight loss and low body weight, but also in patients with normal or increased body mass index. Therefore, the term sarcopenic obesity (SO) is a new definition that further expands the implications of altered body composition. The aim of this study was to assess the impact of SO on the perioperative morbidity and the survival of GC patients undergoing gastrectomy by evaluating body composition on CT images. Preoperative CT scans were obtained from all patients with a diagnosis of GC undergoing gastrectomy with curative intent between January 2012 and December 2019. Skeletal muscle mass index (SMMI) and visceral adipose tissue (VAT) cross-sectional area at the level of the transverse processes of the third lumbar vertebra (L3) were measured. Sarcopenia and obesity were defined according to sex-specific cut-off points. After analysing 190 patients, the prevalence of SO was 21.1% (40 patients) and sarcopenia was 14.7% (28 patients). Multivariate analysis showed that corporal composition was an independent factor of overall survival (p = 0.049). Logistic regression was performed to identify risk factors associated with postoperative complications. SO was identified as a risk factor for serious Clavien-Dindo complications > IIIb/IV [OR 2.82 (1.1-7.1); p = 0.028]. SO was a risk factor for severe postoperative complications as well as worse long-term oncological after a gastrectomy for GC.


Genetic counseling in segmental neurofibromatosis.
We report two patients with segmental neurofibromatosis and review the literature with regard to possible hereditary transmission of this disorder. Patients that meet strict criteria for the diagnosis of segmental neurofibromatosis seem to have a low probability of transmitting the disease. We emphasize the importance of establishing and strictly adhering to a set of diagnostic criteria and of obtaining a comprehensive family history when reporting cases of segmental neurofibromatosis.


Parent influence on concussion reporting in first-year collegiate athletes.
To assess the relationship between sport-parenting practices and concussion reporting intentions of collegiate athletes across two levels of competition. Entering first-year student-athletes (varsity and club) at a mid-sized university in the Southeast region of the United States (n = 327). Written surveys were completed prior to the start of the 2015 academic year. Structural equation modeling was used to test a model predicting concussion-reporting intentions. College athletes were more likely to intend to report a suspected concussion when they believed their parents wanted them to report (B=-0.88, SD = 0.94), and when they experienced less sport achievement pressure from their parents (B=-0.12, SD = 8.07). Parents influence the concussion safety of entering collegiate athletes at both the varsity and club level. Lower pressure sport parenting prior to college entry may help foster safer concussion reporting behaviors and may be an appropriate target for future intervention development work.


The binding of urate by plasma proteins.
Protein binding of urate may have some pertinence to the pathogenesis of gout. However, binding studies have been hampered by problems with in vitro methodology and by the problem of relating the results of in vitro studies to the physiological situation. In the present study urate binding was determined by an ultrafiltration procedure. All manipulations were performed anaerobically and at 37 degrees in order to maintain the sample under physiological conditions. Normal urate bound was 15 +/- 7.5% in males and 10 +/- 6.6% in females. Urate binding did not correlate significantly with either the albumin or total urate concentration. It is suggested that the interaction between protein and urate is influenced by a number of factors other than the concentrations of free urate and binding protein. Some possible ones are discussed. The techniques described might usefully be applied to a study of urate binding in various pathological states.


Extremely low frequency pulsed electromagnetic fields increase cell proliferation in lymphocytes from young and aged subjects.
The effect of the in vitro exposure to extremely low frequency pulsed electromagnetic fields (PEMFs) on the proliferation of human lymphocytes from 24 young and 24 old subjects was studied. The exposure to PEMFs during a 3-days culture period or during the first 24 hours was able to increase phytohaemagglutinin-induced lymphocyte proliferation in both groups. Such effect was greater in lymphocytes from old people which showed a markedly reduced proliferative capability and, after PEMF exposure, reached values of 3H-TdR incorporation similar to those of young subjects. The relevance of these data for the understanding and the reversibility of the proliferative defects in cells from aged subjects and for the assessment of risk related to the environmental exposure to PEMFs has to be considered.


Simultaneous determination of UDCA and its major metabolites in human plasma with surrogate matrix by a rapid and specific LC-MS/MS method.
A rapid, convenient, and specific liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of ursodeoxycholic acid (UDCA), and its major metabolites, glycoursodeoxycholic acid (GUDCA) and tauroursodeoxycholic acid (TUDCA) in human plasma. Methanol was chosen as surrogate matrix for preparation the calibrators to establish calibration curves. Isotope internal standard was used for each analyte. After plasma samples were deproteinized with methanol, the post-treatment samples were analyzed on a ZORBAX SB-C18 column (2.1 × 50 mm, 1.8 μm) with 2 mM ammonium acetate and acetonitrile as mobile phase at a flow rate of 0.5 mL/min. Detection was performed on a triple quadrupole mass spectrometer operating in multiple reaction monitoring (MRM) employing negative ESI interface using API5500 triple quadrupole tandem mass spectrometer system, with the transitions set at m/z 391.4 → m/z 391.4, m/z 448.3 → m/z 73.9, m/z 498.4 → m/z 80.1, m/z 395.3 → m/z 395.3, m/z 453.3 → m/z 74.0, and m/z 503.2 → m/z 79.9 for UDCA, GUDCA, TUDCA, UDCA-d4, GUDCA-d5, and TUDCA-d5, respectively. The calibration curve ranges were 5.00-2500 ng/mL for UDCA and GUDCA and 0.500-250 ng/mL for TUDCA. The intra- and inter-day precision was within 7.00% in terms of relative standard deviation (RSD%) and the accuracy within 11.75% in terms of relative error. The selectivity, sensitivity, extraction recovery, matrix effect, dilution reliability, and stability were within the acceptable range. The method was successfully applied to a pharmacokinetic study in 12 healthy Chinese volunteers after oral administration of 250 mg UDCA.


Time to surgery is not an oncological risk factor in HCC patients undergoing liver resection.
Given limitations of the health care systems in case of unforeseeable events, e.g., the COVID pandemic as well as trends in prehabilitation, time from diagnosis to surgery (time to surgery, (TTS)) has become a research issue in malignancies. Thus, we investigated whether TTS is associated with oncological outcome in HCC patients undergoing surgery. A monocentric cohort of 217 patients undergoing liver resection for HCC between 2009 and 2021 was analyzed. Individuals were grouped according to TTS and compared regarding clinical characteristics. Overall survival (OS) and recurrence-free survival (RFS) was compared using Kaplan-Meier analysis and investigated by univariate and multivariable Cox regressions. TTS was not associated with OS (p=0.126) or RFS (p=0.761) of the study cohort in univariate analysis. In multivariable analysis age (p=0.028), ASA (p=0.027), INR (0.016), number of HCC nodules (p=0.026), microvascular invasion (MVI; p<0.001), and postoperative complications (p<0.001) were associated with OS and INR (p=0.005), and number of HCC nodules (p<0.001) and MVI (p<0.001) were associated with RFS. A comparative analysis of TTS subgroups was conducted (group 1, ≤30 days, n=55; group 2, 31-60 days, n=79; group 3, 61-90 days, n=45; group 4, >90 days, n=38). Here, the median OS were 62, 41, 38, and 40 months (p=0.602 log rank) and median RFS were 21, 26, 26, and 25 months (p=0.994 log rank). No statistical difference regarding oncological risk factors were observed between these groups. TTS is not associated with earlier tumor recurrence or reduced overall survival in surgically treated HCC patients.


Characterization of age-dependent variability in the flank scales of two scorpaeniformes fishes by applying light and scanning electron microscopy imaging.
The morphology of scales from four flank regions in two species of Scorpaeniforme fishes of the family Platycephalidae was studied by applying light and scanning electron microscopy, and the age-dependent variability of scale structures was discussed. The scales of four flank regions from three size classes in both species were ctenoid. The posterior margin of all the ctenoid scales was formed by two rows of cteni, while the three complete rows of cteni were not observed in the examined scales. The cteni of both rows were similar in morphology. Some scale characteristics showed alteration during the fish growth, including the shape of the anterior region of scale in Platycephalus indicus, the presence of lepidonts in Grammoplites suppositus, and the general shape of scale as well as the indices SCL.SCW and JSW.SL in both species. Also, the number of cteni in posterior margin of scales was increased during fish development, while their general morphology did not change significantly. The number of cteni in the scales of small and large fishes in G. suppositus was found to be obviously lower than P. indicus. By considering the function of lepidonts in improving the hydrodynamic efficiency of swimming, it can be assumed that G. suppositus is not probably very active in swimming as P. indicus. As a conclusion, modification in the ornamentations of the posterior region are subject to alteration during the growth of the fish. Besides its developmental changes, some scale characters in the adult forms have taxonomic significance, including the square-shaped scales in P. indicus vs. the oval-shaped scale in G. suppositus; a total of 26-31 radii in the anterior field in P. indicus vs. 11-12 radii in G. suppositus; the presence of many (54-58) cteni in the posterior part in P. indicus vs. a moderate (19-23) cteni in G. suppositus. These characters could be used as additional morphological data to be used for studying systematics and even phylogeny of the flathead fishes.


Tunicate cytokine-like molecules and their involvement in host defense responses.
Tunicates (ascidians or sea squirts) are a large group of invertebrate chordates that are closely related to vertebrates. Their critical phylogenetic position has stimulated substantial interest in their host defense ("immune") responses. Whilst this interest has generated a wealth of knowledge regarding the humoral and cellular mechanisms that undertake defensive responses, there is less known about the regulation of those reactions. This chapter focuses on three cellular responses (cell proliferation, phagocytosis and chemotaxis) that are known to be regulated by cytophilic humoral molecules. Some of the humoral factors that affect these responses have functional and physicochemical similarities to vertebrate cytokines, like interleukin-1. However, the only regulatory molecules that have been characterized at a molecular level bear far greater similarity to C-type lectins or complement components.


A Case of Kounis Type I in a Young Woman With Samter's Triad.
Kounis syndrome is defined as an acute coronary syndrome triggered by allergic or hypersensitivity reactions resulting in mast cell and platelet activation. Numerous causes have been described, including various drugs, medical conditions, and environmental exposures. Samter's triad consists of nasal polyps, asthma, and aspirin (or nonsteroidal anti-inflammatory drug) sensitivity. We describe a case of Kounis type I in a young woman with Samter's triad who presented with cardiac arrest on 3 occasions. Ergonovine provocation testing established the diagnosis of coronary vasospasm. The patient has derived significant benefit from calcium channel blockers.


Three dimensional reconstruction in coronal synostosis: pre and post operative appearances.
Three dimensional computed tomography (CT) is a relatively new method of arranging the elements of CT slices into a morphological image with a multi dimensional appearance. It is of particular use in craniofacial deformities. The following report shows its use in the pre and post operative assessment of frontal skull deformity in three infants with coronal synostosis.


Desiccation tolerant plants in South America.
Numerous Velloziaceae species concentrated in Minas Gerais, Brazil, constitute most of the desiccation tolerant flora of S. America. In the grasses, two Microchloa spp and Tripogon spicatus are desiccation tolerant. Though widespread, they are low growing and appear unimportant. With the exception of Anemia, desiccation tolerant ferns in dry land areas are related to the "resurrection" fern flora reported for N. America. The likely possibility of a desiccation tolerant flora of epiphytic ferns in rain forest areas was not investigated.


Polycystic kidney disease complicates renal pathology in a family with Fabry disease.
Fabry disease is a rare lysosomal storage disorder that primarily affects the heart and kidneys, often presenting with reduced renal function. Polycystic kidney disease is a renal condition in which cysts are found, which have a different presentation than the cysts associated with Fabry disease. We report a 60-year-old male patient who was diagnosed with Fabry disease with the classic c.730G > A (p.Asp244Asn) variant of the GLA gene at 34 years of age. Fabry symptoms in this patient include hypohidrosis, hearing loss, corneal whorling, and edema. He also presented with polycystic kidney disease with multiple simple and mildly complex cysts on abdominal ultrasound. Family history of note included Fabry disease in his mother and maternal uncle as well as polycystic kidneys in his mother. Molecular analysis for polycystic kidney disease revealed a variant of uncertain significance (VUS) in the PKD1 gene. Although the in silico studies of this VUS have inconclusive results, the patient fills clinical criteria of autosomal dominant polycystic kidney disease, therefore, Fabry disease and polycystic kidney disease are considered two co-existing manifestations in this family. This case demonstrates the possibility of two renal comorbidities in the same individual and the risk of one diagnosis being overlooked by the other.


Molecular genetic analysis of human alcohol dehydrogenase.
Human alcohol dehydrogenase (ADH) consists of a complex group of isozymes encoded by at least five non-identical genes, two of which have previously been shown through enzymatic analysis to possess polymorphic variants. Using a cDNA probe the ADH2 gene encoding the beta subunit of human ADH was mapped to human chromosome 4. The cDNA probe for ADH2 was also used to detect a restriction fragment length polymorphism present in human populations. This polymorphism may help establish whether certain ADH allelic variants are linked with certain types of altered alcohol tolerance observed in various individuals. The restriction fragment length polymorphism may also be of use in genetic linkage studies of other genes located near ADH on human chromosome 4.


[Proliferating activity and differentiation between peripheral cells and central cells in ameloblastoma].
To investigate the proliferating activities and differentiation between peripheral cells and central cells in ameloblastoma. Expressions of proliferating cell nuclear antigen (PCNA), Ki-67, CK10&13 and CK19 were detected in 43 ameloblastoma (15 follicular, 20 plexiform and 8 acanthomatous) by SP immunohistochemical methods. The PCNA labelling indices were significantly higher in peripheral cells (5.12% +/- 2.76%) of tumour nests or strands than in central cells (1.36% +/- 1.02%, P < 0.001). The peripheral cells of tumour nests or strands exhibited a significantly higher Ki-67 labelling index (3.63% +/- 1.80%) than central cells (1.26% +/- 0.96%, P < 0.001). The labelling indices between PCNA and Ki-67 showed a significant correlation (P < 0.01). The positive expressions of CK10&13 and CK19 were significantly higher in central cells than in peripheral cells (P < 0.01). The peripheral zones of tumour nests or strands are regarded as proliferating areas; there exists a significantly different differentiation between central cells and peripheral cells.


Clinical features and diagnosis of hairy cell leukemia.
Significant advances in the diagnosis and treatment of hairy cell leukemia (HCL) have recently been made. Improved distinction of HCL from its mimics though clinical presentations, morphologic and immunophenotypic features, and more recently molecular biology, has highlighted marked differences in treatment response and overall prognosis between these disorders. As our understanding of the unique pathobiology of HCL has grown, exciting new avenues of treatment as well as insight into immune function have been obtained. This review provides an overview of the clinical features and diagnostic attributes of HCL, with contrast to other mature B cell lymphoproliferative disorders with overlapping features.


Quantitative waveform measures of the electrocardiogram as continuous physiologic feedback during resuscitation with cardiopulmonary bypass.
There are few if any real-time physiologic measures that currently provide feedback during resuscitation from cardiac arrest. Such measures could be used to guide therapy not simply based on process guidelines but on the physiologic response of the patient from moment to moment. To this end, we applied an existing technology - quantitative waveform measures (QWMs) of the ventricular fibrillation (VF) electrocardiogram (ECG) - as a continuous measure of myocardial response to reperfusion with cardiopulmonary bypass (CPB) after prolonged cardiac arrest. Sixteen domestic, mixed-breed swine were sedated, anesthetized and paralyzed. Mechanical ventilation with room air was provided. Large diameter bypass catheters were placed in the right external jugular vein and right femoral artery for cardiopulmonary bypass (CPB). VF was induced with a 3-s 100mA transthoracic shock and left untreated for 15, 20, 25, or 30min, followed by 10min of centrifugal pump CPB (Bard CPS). Continuous Lead II ECG was recorded with an electronic data acquisition system (Power Lab, ADInstruments). Four QWMs representing 4 signal characteristics of the VF ECG were calculated in 5-s windows throughout the course of untreated VF and resuscitation with CPB. Four animals were assigned to each VF duration group. QWM recovery was inversely correlated with untreated VF duration, and was drastically reduced above 20min of untreated VF. Return of spontaneous circulation (ROSC) was highly unlikely after 20min of untreated VF. QWMs of the VF ECG provided a real-time metric of myocardial electrophysiologic response to reperfusion with CPB. Resuscitation from greater than 20min of untreated cardiac arrest was unlikely. QWMs may be useful for titrating CPB duration before defibrillation and assessing CPR quality independently of process guidelines.


DICE: Dual mTorc Inhibition in advanCed/recurrent Epithelial ovarian cancer resistant to standard treatment-a study protocol for a randomised trial investigating a novel therapy called TAK228.
The standard initial treatment for ovarian cancer is surgery and platinum-based chemotherapy and potentially maintenance therapy with avastin or inhibitors of poly-ADP ribose polymerase (PARP). While a proportion of women are cured by this approach, the vast majority will relapse and become resistant to platinum chemotherapy either initially or on subsequent treatment. There is an unmet need to improve response to treatment and quality of life in these women. TAK228 is a novel therapy that can be added to standard treatment in the participant population and the aim of the DICE trial is to assess its effectiveness. Laboratory and clinical research has shown that these ovarian cancers may respond to the molecular target of a drug such as TAK228, and there have been studies using it in other advanced solid tumours including endometrial cancer. One hundred twenty-four eligible women will be recruited from participating research sites in the United Kingdom (UK) and Germany. Randomised participants will receive either weekly paclitaxel alone (standard treatment, n = 62) or TAK228 plus weekly paclitaxel (n = 62) until the cancer significantly worsens; there are significant adverse events or any other protocol-defined stopping criteria. Participants will be monitored for response to treatment (using radiological imaging), adverse events and quality of life during both randomised treatment and subsequent follow-up. The primary objective/endpoint of the study is to compare the two treatments in terms of progression-free survival, or the length of time that each participant is alive without the cancer significantly worsening according to defined assessment criteria. If the addition of TAK228 to weekly paclitaxel chemotherapy is shown to significantly improve this statistically, and adverse events and quality of life are not significantly worse than standard treatment, then TAK228 plus weekly paclitaxel could potentially be taken forward within the context of a larger phase III trial. ClinicalTrials.gov NCT03648489 . Registered on 27 August 2018.


Prompt treatment of intestinal obstruction after biliopancreatic diversion can save the intestinal loop.
Bariatric surgery is becoming an accepted method for weight reduction. Biliopancreatic diversion is reserved for high initial BMI. With the increasing number of these procedures, the reports of complications become more important and prepare a wider range of specialties to deal with them. We report a 62-year-old woman who developed a volvulus of the biliopancreatic loop after a biliary diversion operation with a sleeve gastrectomy and antro-ileal anastomosis. Symptoms of biliopancreatic loop obstruction are rather vague, presenting with atypical abdominal pain, nausea, sometimes vomiting, preserved bowel motility, stool, and gas passage and normal upper GI X-ray. Due to the patient's prompt reaction and straight referral to a bariatric surgeon, freeing of the loop was enough to maintain its viability. The patient's further recovery and follow-up were uneventful. With this case, we stress the importance of an expert in such cases and a need to consider familiarizing doctors with these patients and with the peculiarities of their treatment.


The interplay of goal-driven and stimulus-driven influences on spatial orienting.
Search for a target stimulus among distractors is subject to both goal-driven and stimulus-driven influences. Variables that selectively modify these influences have shown strong interaction effects on saccade trajectories toward the target, suggesting the involvement of a shared spatial orienting mechanism. However, subsequent manual response times (RTs) have revealed additive effects, suggesting that different mechanisms are involved. In the present study, we tested the hypothesis that an interaction for RTs is obscured by preceding multisaccade trajectories, promoted by the continuous presence of distractors in the display. In two experiments, we compared a condition in which distractors were removed soon after the presentation of the search display to a standard condition in which distractors were not removed. The results showed additive goal-driven and stimulus-driven effects on RTs in the standard condition, but an interaction when distractors were removed. These findings support the view that both variables influence a shared spatial orienting mechanism.


Spine surgery under neuraxial vs. general anesthesia: the current state of comparative outcomes research.
The impact of primary anesthetic technique on outcomes after spine surgery is controversial. Given frequent calls for well designed prospective comparative studies of neuraxial anesthesia vs. general anesthesia and recent reports of 'awake spine surgery' successes in the surgical literature, an updated evidence review is indicated. Systematic reviews, population-based and retrospective cohort studies suggest few significant differences in important complications or global recovery between anesthetic techniques. On the basis of overall low-to-moderate quality evidence, neuraxial anesthesia is associated with statistically significant benefits for several individual outcomes compared with general anesthesia, including improved intraoperative hemodynamic stability, less postoperative nausea and vomiting, lower early pain scores and shorter length of hospital stay. There are ongoing calls for well designed, adequately powered prospective studies. Our understanding of the risks, benefits and comparative outcomes between neuraxial anesthesia and general anesthesia for spine surgery is evolving. Although the results derived from this body of literature suggest specific benefits of neuraxial anesthesia, further research is required before widespread recommendations for either technique can be made. Until then, both neuraxial anesthesia and general anesthesia are reasonable choices for lumbar spine surgery of short duration, in appropriately selected patients.


Epidermal growth factor signalling pathway in endochondral ossification: an evidence-based narrative review.
During endochondral bone development, a complex process that leads to the formation of the majority of skeletal elements, mesenchymal cells condense, differentiating into chondrocytes and producing the foetal growth plate. Chondrocytes progressively hypertrophy, induce angiogenesis and are then gradually replaced by bone. Epidermal Growth Factor (EGF), one of many growth factors, is the prototype of the EGF-ligand family, which comprises several proteins involved in cell proliferation, migration and survival. In bone, EGF pathway signalling finely tunes the first steps of chondrogenesis by maintaining mesenchymal cells in an undifferentiated stage, and by promoting hypertrophic cartilage replacement. Moreover, EGF signalling modulates bone homeostasis by stimulating osteoblast and osteoclast proliferation, and by regulating osteoblast differentiation under specific spatial and temporal conditions. This evidence-based narrative review describes the EGF pathway in bone metabolism and endochondral bone development. This comprehensive description may be useful in light of possible clinical applications in orthopaedic practice. A deeper knowledge of the role of EGF in bone may be useful in musculoskeletal conditions which may benefit from the modulation of this signalling pathway.Key messagesThe EGF pathway is involved in bone metabolism.EGF signalling is essential in the very early stages of limb development by maintaining cells in an undifferentiated stage.EGF pathway positively regulates chondrocyte proliferation, negatively modulates hypertrophy, and favours cartilage replacement by bone.EGF and EGF-like proteins finely tune the proliferation and differentiation of bone tissue cells, and they also regulate the initial phases of endochondral ossification.


On-line data acquisition and evaluation of long-term measurements of circadian rhythms in individual cells of Acetabularia.
A multitasking time-sharing computer system was implemented for studies of different circadian rhythms in individual cells of the unicellular green alga, Acetabularia. This fully automatized system allows simultaneous data acquisition and analysis. Graphical presentation of untreated and mathematically treated data is permanently available on three graphic displays and on a digital plotter. The sampling rate for the data acquisition in each of the 60 channels connected to the system is 720/24 h. Provisions have been made to guarantee uninterrupted data uptake for these long-term measurements by including an auto-restart module and by providing extremely reliable software for the experimenter using menu techniques.


An international capstone experience for pharmacy students.
This report describes the experiences of the University of Tennessee College of Pharmacy over 20 years with an international capstone educational experience for students. Although the university provides reciprocal opportunities to international students, this report focuses on the experiences of the college's pharmacy students who have participated in the program. This capstone course is offered as an elective course in the advanced pharmacy practice experience (APPE) component of the college's experiential program. Goals of the program and a brief description of its organizational structure are provided. Results of a structured student satisfaction survey and a survey covering the most recent 3 years of the program are presented. This program has greatly broadened participants' cultural horizons and expanded their global view and understanding of the contributions of pharmacy to health care.


Accuracy of accelerated cine MR imaging at 3 Tesla in longitudinal follow-up of cardiac function.
The ability of fast, parallel-imaging-based cine magnetic resonance (MR) to monitor global cardiac function in longitudinal exams at 3 Tesla was evaluated. Seventeen patients with chronic cardiac disease underwent serial cine MR imaging exams (n=3) at 3 Tesla. Data were acquired in short-axis orientation using cine steady-state free precession (SSFP) with a spatial resolution of 2.5 x 1.9 mm(2) at 45 ms temporal resolution. Multislice imaging (three slices/breath-hold) was performed using TSENSE acceleration (R=3) and standard single-slice cine (non-TSENSE) was performed at identical locations in consecutive breath-holds. End-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF) and myocardial mass (MM) of both cine approaches were compared for individual time-points as well as for longitudinal comparison. TSENSE-cine did not show significant differences for EDV (2.6 ml; P=0.79), ESV (2.2 ml; P=0.81), EF (-0.3%; P=0.95) and MM (2.4 g; P=0.72) in comparison with non-TSENSE. Longitudinal ANOVA analysis did not reveal significant differences for any parameter, neither for non-TSENSE data (all P>0.7) nor for TSENSE data (all P>0.9). Multifactorial ANOVA showed non-significant differences (all P>0.7) at comparable data variances. Data acquisition was significantly shortened using TSENSE. Threefold accelerated multislice cine at 3 Tesla allows accurate assessment of volumetric LV data and accurate longitudinal monitoring of global LV function at a substantially shorter overall examination time.


Molecular characterisation of methicillin-sensitive Staphylococcus aureus from deep surgical site infections in orthopaedic patients.
Staphylococcus aureus is a leading cause of surgical site infections (SSIs). The association between S. aureus genotypes and the severity of illness is, however, incompletely understood. The aim of the study was to genotype S. aureus isolates from deep SSI in orthopaedic patients to identify molecular markers associated with invasive S. aureus infections. DNA microarray analysis was performed on S. aureus isolates collected from 60 patients with deep SSI following major orthopaedic surgery, while 57 isolates from nasal carriers served as controls. Genes associated with antibiotic resistance, adhesion, immune evasion, tissue invasion and toxin production were detected. The bone sialoprotein-binding protein gene (bbp) was more frequent in isolates from SSI patients compared to nasal carriers (95.0% vs. 82.5%), suggesting a role in invasive disease. No major differences in other molecular virulence markers could be distinguished among isolates from the two clinical groups, suggesting that any S. aureus strain may cause invasive infection. Our study reveals important genotypic information on isolates obtained from deep SSI following orthopaedic procedures.


Predictors of metastasis to lymph nodes posterior to the right recurrent laryngeal nerve in differentiated thyroid carcinoma: A prospective study.
To study the clinicopathological characteristics and the risk factors of lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) metastasis in differentiated thyroid carcinoma; and to identify the indication for LN-prRLN dissection. We treated 145 patients with differentiated thyroid carcinoma with appropriate surgical intervention. The specimens were examined by the pathologists. The right paratracheal lymph nodes were divided into two groups: anterior or posterior to right recurrent laryngeal nerve (VIa or VIp compartment, respectively). We recorded the clinical characteristics, histopathological features of the primary tumors, and lymph node metastasis of the patients. The results were statistically analyzed. There were 85 patients (58.6%) with central lymph node metastasis, of whom 61 (42.1%) had metastasis in VIa compartment; 16 patients (11.0%) had VIp subdistrict metastasis; and 25 patients had lateral lymph node metastasis. Multiplicity, larger tumor (≥1 cm), and coexistence of central lymph node metastasis, VIa compartment metastasis, and lateral lymph node metastasis were all significantly related with LN-prRLN metastasis, while sex, age, location of the tumor, and extrathyroid extension of the tumor showed no significant relation (p > 0.05). The incidence of LN-prRLN metastasis was lower than other central lymph nodes, as well as lymph nodes anterior to right recurrent laryngeal nerve. When there were multiple foci of tumors, or the tumor was larger than 1 cm, or central or lateral LN metastasis was indicated by preoperative ultrasound or confirmed by intraoperative frozen sections, it is strongly recommended that exploration and dissection of the LN-prRLN should only be performed by experienced surgeons.


[Demonstration of thrombocyte membrane proteins with monoclonal antibodies by a flow cytometry bioassay].
Formation of a hemostatic plug is triggered by platelets. Platelet function (e.g. adhesion, aggregation) depends essentially on membrane bound receptor proteins. Conventional chromatographic analysis of these glycoprotein macromolecules is difficult and not appropriate for diagnostic routine. In combination of cytoflowmetric single cell analysis with monoclonal staining we developed a bio-assay for qualitative and semi-quantitative analysis of glycoprotein IB and IIB/IIIA on vital fixed platelets. The expression of these molecules was evaluated in 20 healthy volunteers. The assay offers for the first time the possibility of screening the expression of receptor proteins on platelet membranes, which are related to indicate either a functional lack in bleeding disorders or a prethrombotic state due to an enhanced functional potential in high risk patients.


Corneal Endothelial Cell Loss After Endocapsular and Supracapsular Phacoemulsification: The PERCEPOLIS Randomized Clinical Trial.
Subluxation techniques are superior to divide-and-conquer in procedure duration, pain, and ultrasound quantity, but their safety in endothelial cell loss (ECL) is unclear. This randomized single-blind noninferiority clinical trial aimed to determine whether subluxation supracapsular phacoemulsification techniques are inferior to a reference endocapsular technique (divide-and-conquer) regarding postoperative corneal ECL. Patients (aged18 years or older) with greater than +0.2 logarithm of the minimum angle of resolution best spectacle-corrected visual acuity and normal to severe density cataract were randomized to subluxation or divide-and-conquer phacoemulsification in 2015 to 2016. Follow-up with ophthalmic tests was conducted on day 4 and months 1, 3, and 12. The primary study outcome was ECL at all time points. Secondary study end points were operative variables, including effective phaco time and procedure duration. A clinically relevant noninferiority ECL limit was established on the basis of the literature. In total, 292 patients (mean age, 73 yrs; 59% female) were randomized and underwent subluxation (n = 148) or divide-and-conquer (n = 144). Day 4 and month 1, 3, and 12 data were available for 243, 270, 275, and 198 patients, respectively. The unexpectedly high dropout at 12 months meant that the 12-month ECL data could only be assessed qualitatively. Surgery was successful in all patients. Subluxation was noninferior to divide-and-conquer in ECL. Effective phaco times were similar, but subluxation associated with shorter procedure duration. The subluxation technique was noninferior to divide-and-conquer regarding postoperative ECL, at least in the first 3 months, and associated with reduced intervention time. Subluxation techniques may be suitable alternatives to endocapsular techniques.Clinical Trial Registration-URL: ClinicalTrials.gov. Unique identifier: NCT02535819.


Infantile acid maltase deficiency. III. Ultrastructure of metachromatic material and glycogen in muscle fibers.
In infantile acid maltase deficiency (AMD), masses of glycogen accumulate in muscle fibers and are then gradually digested. The metachromatic material found in some glycogen-filled fibers, not previously studied with the electron microscope, has two different fine structural appearances. Some is similar in shape and size to glycogen beta granules, but is more intensely stained, and some is in larger granules, irregular in shape, and has even higher stain affinity. Since acid maltase deficiency was identified by Hers, others have proposed that more than one genetic defect or additional extralysosomal factors are required to account for massive glycogen accumulation and metachromasia. There is no direct evidence of additional rare genetic defects. Presented herein are two simple proposals consistent with the primary deficiency. The first is that some partly digested glycogen is condensed and that this concentrates the sites that bind dye, producing metachromasia and other differences from normal glycogen. The second is that the massive accumulation of glycogen in muscle fibers involves, in addition to previously recognized lysosomal storage and lysosomal rupture, inactivation of sarcoplasmic phosphorylase caused by disruption of excitation-contraction linkages. These two proposals are physiologically plausible and potentially testable and do not invoke the coincidence of two or more rare genetic mutations.


Arthroscopically Assisted, Minimally Invasive Percutaneous Fixation of a Patellar Fracture.
Operative fixation of a patellar fracture can be accomplished through a variety of techniques. However, drawbacks have been associated with many of these techniques, including painful hardware, poor skin healing due to bruising and swelling, inadequate cartilage reduction, and eventual post-traumatic osteoarthritis. Throughout the orthopaedic field, minimally invasive approaches have become popular. We describe an arthroscopically assisted method for ensuring fracture reduction intraoperatively and addressing associated defects while the patella is stabilized using a minimally invasive percutaneous fixation technique with screws and a tension band construct.


Bacteriophytochromes control conjugation in Agrobacterium fabrum.
Bacterial conjugation, the transfer of single stranded plasmid DNA from donor to recipient cell, is mediated through the type IV secretion system. We performed conjugation assays using a transmissible artificial plasmid as reporter. With this assay, conjugation in Agrobacterium fabrum was modulated by the phytochromes Agp1 and Agp2, photoreceptors that are most sensitive in the red region of visible light. In conjugation studies with wild-type donor cells carrying a pBIN-GUSINT plasmid as reporter that lacked the Ti (tumor inducing) plasmid, no conjugation was observed. When either agp1(-) or agp2(-) knockout donor strains were used, plasmid DNA was delivered to the recipient, indicating that both phytochromes suppress conjugation in the wild type donor. In the recipient strains, the loss of Agp1 or Agp2 led to diminished conjugation. When wild type cells with Ti plasmid and pBIN-GUS reporter plasmid were used as donor, a high rate of conjugation was observed. The DNA transfer was down regulated by red or far-red light by a factor of 3.5. With agp1(-) or agp2(-) knockout donor cells, conjugation in the dark was about 10 times lower than with the wild type donor, and with the double knockout donor no conjugation was observed. These results imply that the phytochrome system has evolved to inhibit conjugation in the light. The decrease of conjugation under different temperature correlated with the decrease of phytochrome autophosphorylation.


Clinical development of fulvestrant ("Faslodex").
This paper outlines the development of fulvestrant, the first in a new class of antioestrogen agents with no agonist effects, to be used for the treatment of hormone receptor-positive advanced breast cancer in postmenopausal women. The role of the oestrogen receptor in breast cancer growth and development and the evolution of pharmacological strategies to manipulate it are also discussed. Preclinical and clinical evidence for the efficacy of fulvestrant are also reviewed, along with the tolerability profile of this agent in relation to other endocrine therapies. Further research will define the role of this exciting new agent in the endocrine treatment of breast cancer.


Neural cell markers and their applications to neurology.
Cell-type-specific antigenic markers which allow the unambiguous identification of the major neural cell types in dissociated cell cultures of central nervous system (CNS) and peripheral nervous system (PNS) tissues from a variety of animal species have recently been established. The use of many of these markers has also been extended to nervous tissue sections in which the in vivo properties of neural cells can be studied. Markers may be either cell surface or intracellular components of neural cells. Cell surface markers can be used to separate different cell types to produce purified cell populations. The ability of monoclonal antibodies to recognise single antigenic determinants is likely to prove superior to conventional heteroantisera in recognising cell surface antigens. Although the present techniques have intrinsic limitations, nonetheless both surface and intracellular markers should prove to be of great value in a wide range of biological and clinical neurological studies.


Collagens, stromal cell-derived factor-1alpha and basic fibroblast growth factor increase cancer cell invasiveness in a hyaluronan hydrogel.
Beyond to control of cell migration, differentiation and proliferation, the extracellular matrix (ECM) also contributes to invasiveness of human cancers. As the roles of hyaluronan (HA) and collagens in this process are still controversial, we have investigated their involvement in cancer pathogenesis. With this aim in view, we developed a three-dimensional matrix, as reticulate HA hydrogel alone or coated with different collagens, in which cells could invade and grow. We show that cancer cells, which were non-invasive in a single HA hydrogel, acquired this capacity in the concomitant presence of type I or III collagens. Both types of ECM compound, HA and collagens, possess the capacity to stimulate production of metalloprotease-2, recognized otherwise as a factor for poor cancer prognosis. HA-provoked cellular invasiveness resulted from CD44-mediated increase in cytosolic [Ca2+] and its subsequent hydrolysis due to ADAM (a disintegrin and metalloprotease) proteolytic activity. Interestingly, this mechanism seemed to be absent in non-invasive cancer cell lines. Furthermore, using basic fibroblast growth factor and stromal cell-derived factor-1alpha, we also show that this three-dimensional reticulate matrix may be considered as a valuable model to study chemokinetic and chemotactic potentials of factors present in tumour stroma.


Alkaloid constituents from Viola tianschanica.
Eighteen previously undescribed alkaloids, tishaviolamines A-J, including eight pairs of enantiomers, together with two known benzylisoquinoline alkaloids, (-)-bicuculline and (-)-corlumine, were isolated from Viola tianschanica. Among them, tishaviolamine A-E were demonstrated to possess three types of unpresented skeletons. The structures of these alkaloids were established by comprehensive analyses of the 1D, 2D-NMR and (+)HRESIMS data. The absolute configurations of enantiomers were determined by comparing their calculated ECD spectra with the experimental ones. The menin-mixed lineage leukemia 1 protein-protein interaction inhibitory effect of the isolated compounds were also measured.


Intermittent abdominal pressure ventilation management in neuromuscular diseases: a Delphi panel Consensus.
Intermittent abdominal pressure ventilator (IAPV) use started in the 1930s for ventilatory assistance with muscular dystrophy patients. Later, the device was perfected and expanded for other neuromuscular disorders (NMD). In recent years, the morbidity and mortality tracheotomies and trach tubes related renewed the interest around IAPV. However, there are no guidelines for its use. This study aimed to establish a consensus among physicians involved in its practice to provide IAPV suggestions for the treatment of patients with NMD. A 3-step modified Delphi method was used to establish consensus. Fourteen respiratory physicians and one psychiatrist with strong experience in IAPV use and/or who published manuscripts on the topic participated in the panel. A systematic review of the literature was carried out according to the PRISMA to identify existing evidence on IAPV for patients with neuromuscular disorders. In the first round, 34 statements were circulated. Panel members marked 'agree' or 'disagree' for each statement and provided comments. The agreement was reached after the second voting session for all 34 statements. Panel members agreed and IAPV indications, parameter settings (including procedure protocol), potential limitations, contraindications, complications, monitoring, and follow-up are described. This is the first expert consensus on IAPV.


A mobility-based classification of closed kinematic chains in biomechanics and implications for motor control.
Closed kinematic chains (CKCs), links connected to form one or more closed loops, are used as simple models of musculoskeletal systems (e.g. the four-bar linkage). Previous applications of CKCs have primarily focused on biomechanical systems with rigid links and permanently closed chains, which results in constant mobility (the total degrees of freedom of a system). However, systems with non-rigid elements (e.g. ligaments and muscles) and that alternate between open and closed chains (e.g. standing on one foot versus two) can also be treated as CKCs with changing mobility. Given that, in general, systems that have fewer degrees of freedom are easier to control, what implications might such dynamic changes in mobility have for motor control? Here, I propose a CKC classification to explain the different ways in which mobility of musculoskeletal systems can change dynamically during behavior. This classification is based on the mobility formula, taking into account the number of loops in the CKC and the nature of the constituent joint mobilities. I apply this mobility-based classification to five biomechanical systems: the human lower limbs, the operculum-lower jaw mechanism of fishes, the upper beak rotation mechanism of birds, antagonistic muscles at the human ankle joint and the human jaw processing a food item. I discuss the implications of this classification, including that mobility itself may be dynamically manipulated to simplify motor control. The principal aim of this Commentary is to provide a framework for quantifying mobility across diverse musculoskeletal systems to evaluate its potentially key role in motor control.


A genetic dissection of the photophobic response of Paramecium tetraurelia.
Paramecium tetraurelia displayed two behavioral responses upon the initiation of a light stimulus at 7 x 10(4) lux. The cells exhibited a photophobic response in the form of behavioral avoiding reactions, followed by an increase in forward swimming velocity that was significantly higher than prior to the light stimulus activation. It was determined that an intensity of approximately 6.5 x 10(3) lux was required to initiate a moderate avoidance behavioral response. Following the avoiding response, a gradual increase in speed occurred as the intensity increased, indicating that increased swimming speeds are dependent on the light intensity. Two mutants, pawnA and Dancer, were utilized since they affect known Ca(2+)-currents of the cell. The use of pawnA cells, which lack voltage-dependent Ca(2+) channel activity, showed that the two responses to light could be genetically separated, in that the cells showed no avoiding reactions, but did increase their swimming speed. The Dancer cells, which display exaggerated Ca(2+) channel activity, exhibited similar initial avoiding responses as the wild type cells, however did not increase their swimming speed as the intensity of the light was increased. This phenotype as replicated in wildtype cells that had been placed in 25 μM 8-Br-cGMP. These data demonstrate that the photophobic light response of Paramecium tetraurelia can be genetically dissected as a means of elucidating the molecular mechanisms of the light response.


Quantification of health risks in Ecuadorian population due to dietary ingestion of arsenic in rice.
In Ecuador alone, 500,000 people in rural areas are estimated to have been exposed to high concentrations of As from water and food, but no quantitative evaluation of health risk has yet been made. The present study quantifies exposure and health risk for the Ecuadorian population from the ingestion of arsenic in white rice. Estimated exposure is correlated with published data on tap water quality and biomarkers of exposure for the population of two towns in the metropolitan area of Quito. Estimated daily intake (EDI) of arsenic for infants living in urban areas of Ecuador is around four times that of European infants, being equal for those livings in rural areas. EDI for the population as a whole is almost twice that of Europe, but between a half and a third of that of Brazil, Bangladesh, and India. Estimated excess lifetime risk (ELTR) for adults is 3 per 10,000, while for infants varies between 10 per 10,000 in rural areas and 20 per 10,000 in urban areas. Future research on arsenic impacts on human health in Ecuador should consider in particular poor populations living in regions where environmental arsenic concentrations are highest, including cross-sectional and longitudinal epidemiologic studies.


Biological implications of long-term anthelmintic treatment: what else besides resistance are we selecting for?
Long-term intensive use of anthelmintics for parasite control of livestock, companion animals, and humans has resulted in widespread anthelmintic resistance, a problem of great socioeconomic significance. But anthelmintic therapy may also select for other biological traits, which could have implications for anthelmintic performance. Here, we highlight recent examples of changing parasite dynamics following anthelmintic administration, which do not fit the definition of anthelmintic resistance. We also consider other possible examples in which anthelmintic resistance has clearly established, but where coselection for other biological traits may have also occurred. We offer suggestions for collecting more information and gaining a better understanding of these phenomena. Finally, we propose research questions that require further investigation and make suggestions to help address these knowledge gaps.


Viral determinants of virulence for Rift Valley fever (RVF) in rats.
Rift Valley fever viral strains or variants (RVFV) were compared with respect to (a) virulence for Wistar-Furth rats; (b) in vitro sensitivity to rat and human interferon; (c) ability to form plaques in primary hepatocyte cultures from genetically resistant or susceptible rat strains, and (d) replicative potential in continuous rat cell lines. Egyptian strains were highly virulent for Wistar-Furth rats; relatively resistant to rat interferon-alpha/beta; capable of producing plaques in primary hepatocyte monolayers; and, in general, replicated more rapidly than the low-virulent, sub-Saharan strains. Virtually all strains from sub-Saharan Africa were sensitive to rat interferon and did not form plaques in rat hepatocyte monolayers. An exception was the 2269/74 strain from Zimbabwe, which had characteristics of the Egyptian strains including increased virulence for Wistar-Furth rats. The relative virulence of RVFV strains for rats did not correlate with interferon sensitivity when human recombinant interferon-alpha was tested on A-549 cells. Thus, several in vitro phenotypic characteristics of RVFV strains tend to correlate with virulence for Wistar-Furth rats and with geographical origin of the viral strains.


Patient-reported outcomes post axillary block dissections for skin cancer.
There are limited studies that look at morbidities in patients who have undergone axillary lymph node dissection (ALND) for skin cancer. To date, there has been no study examining the functional status of the upper limb postoperatively. This study studies the disability in upper limb function of patients postoperatively and looks for factors that influence this. Twenty-five patients who have undergone level I-III ALND were interviewed using the Disability of Arm, Shoulder and Hand (DASH) and European Quality of Life (EuroQol) questionnaires to determine their upper limb functional status and overall quality of life. These data were then compared with epidemiological and surgical factors collected from the patients' notes retrospectively to look for influencing factors. The majority of patients had low disability scores, with only 12% of patients having a score of 40 and above (out of 100). Age of patient, seniority of operator, surgery on the same side of hand dominance, seroma formation and physiotherapy had no significant effect on DASH scores. A higher DASH score was associated with the patients viewing themselves as 'less healthy'. ALND for cutaneous skin cancers does not result in a significant increase in upper limb disability in the majority of patients.


[Sensitization of mouse splenocytes to normal tissue antigens and natural killer activity. I. The effect of immunization with normal syngeneic tissues].
Immunization of C3HA mice with homogenized syngeneous liver led to sensibilization of splenocytes towards liver antigens and to the increase in natural killer cell activity towards K-562 cells. The dynamics of sensibilization and cytotoxicity in different time intervals after immunization has led to a conclusion about a correlation between the two above phenomena.


Increase in the glucosylated form of erythrocyte Cu-Zn-superoxide dismutase in diabetes and close association of the nonenzymatic glucosylation with the enzyme activity.
Human erythrocytes contain glucosylated and nonglucosylated Cu-Zn-superoxide dismutases which can be separated by boronate affinity chromatography. The percentage of the glucosylated form is significantly increased in the erythrocytes of patients with diabetes as compared to normal erythrocytes. The nonglucosylated form of Cu-Zn-superoxide dismutase, which was washed through the boronate column, was glucosylated in vitro upon exposure to radioactive or non-radioactive D-glucose. Incorporation of D-glucose into the protein was observed, and with the increase in glucosylation, the enzymatic activity decreased, indicating that the glucosylation of the enzyme led to a low active form. This is the first demonstration that superoxide dismutase is glucosylated in erythrocytes and that the glucosylation leads to the inactivation of the enzyme.


Covid-19 vaccination and menstrual cycle length in the Apple Women's Health Study.
COVID-19 vaccination may be associated with change in menstrual cycle length following vaccination. We estimated covariate-adjusted differences in mean cycle length (MCL), measured in days, between pre-vaccination cycles, vaccination cycles, and post-vaccination cycles within vaccinated participants who met eligibility criteria in the Apple Women's Health Study, a longitudinal mobile-application-based cohort of people in the U.S. with manually logged menstrual cycles. A total of 9652 participants (8486 vaccinated; 1166 unvaccinated) contributed 128,094 cycles (median = 10 cycles per participant; inter-quartile range: 4-22). Fifty-five percent of vaccinated participants received Pfizer-BioNTech's mRNA vaccine, 37% received Moderna's mRNA vaccine, and 8% received the Johnson & Johnson/Janssen (J&J) vaccine. COVID-19 vaccination was associated with a small increase in MCL for cycles in which participants received the first dose (0.50 days, 95% CI: 0.22, 0.78) and cycles in which participants received the second dose (0.39 days, 95% CI: 0.11, 0.67) of mRNA vaccines compared with pre-vaccination cycles. Cycles in which the single dose of J&J was administered were, on average, 1.26 days longer (95% CI: 0.45, 2.07) than pre-vaccination cycles. Post-vaccination cycles returned to average pre-vaccination length. Estimated follicular phase vaccination was associated with increased MCL in cycles in which participants received the first dose (0.97 days, 95% CI: 0.53, 1.42) or the second dose (1.43 days, 95% CI: 1.06, 1.80) of mRNA vaccines or the J&J dose (2.27 days, 95% CI: 1.04, 3.50), compared with pre-vaccination cycles. Menstrual cycle change following COVID-19 vaccination appears small and temporary and should not discourage individuals from becoming vaccinated.


The Anatomical Society core regional anatomy syllabus for undergraduate medicine.
The Anatomical Society's core syllabus for anatomy (2003 and later refined in 2007) set out a series of learning outcomes that an individual medical student should achieve on graduation. The core syllabus, with 182 learning outcomes grouped in body regions, referenced in the General Medical Council's Teaching Tomorrow's Doctors, was open to criticism on the grounds that the learning outcomes were generated by a relatively small group of anatomists, albeit some of whom were clinically qualified. We have therefore used a modified Delphi technique to seek a wider consensus. A Delphi panel was constructed involving 'experts' (n = 39). The revised core syllabus of 156 learning outcomes presented here is applicable to all medical programmes and may be used by curriculum planners, teachers and students alike in addressing the perennial question: 'What do I need to know ?'


Regulation of tumor invasion and metastasis in protein kinase C epsilon-transformed NIH3T3 fibroblasts.
Protein kinase C epsilon is an oncogenic, actin nucleating protein that coordinately regulates changes in cell growth and shape. Cells constitutively expressing PKCepsilon spontaneously acquire a polarized morphology and extend long cellular membrane protrusions. Here we report that the regulatory C1 domain of PKCepsilon contains an actin binding site that is essential for the formation of elongate invadopodial-like structures, increased pericellular metalloproteinase activity, in vitro invasion of a Matrigel barrier, and the invasion and metastasis of tumors grown in vivo by PKCepsilon-transformed NIH3T3 fibroblasts in nude mice. While removing this small actin binding motif caused a dramatic reversion of tumor invasion, the deletion mutant of PKCepsilon remained oncogenic and tumorigenic in this experimental system. We propose that PKCepsilon directly interacts with actin to stimulate polymerization and the extension of membrane protrusions that transformed NIH3T3 cells use in vivo to penetrate and degrade surrounding tissue boundaries.


[Visualization of the scapholunate space. Description of a simple radiologic image].
Scapho-lunate diastasis is a radiologic criterium of carpal instability. This paper stresses on the importance of producing an X-ray beam that will be parallel to the scapho-lunate joint and describes a simple radiologic positioning that will be a useful complement to the standard views. This view could be associated with the usual static as well as dynamic radiographs.


Therapeutic approach for digestive system cancers and potential implications of exercise under hypoxia condition: what little is known? a narrative review.
Cancer, like other chronic pathologies, is associated with the presence of hypoxic regions due to the uncontrolled cell growth. Under this pathological hypoxic condition, various molecular signaling pathways are activated to ensure cell survival, such as those that govern angiogenesis, erythropoiesis, among others. These molecular processes are very similar to the physiological response caused by exposure to altitude (natural hypobaric systemic hypoxia), the use of artificial hypoxia devices (systemic normobaric simulated hypoxia) or the delivery of vascular occlusion to the extremities (also called local hypoxia by the blood flow restriction technique). "Tumor hypoxia" has gained further clinical importance due to its crucial role in both tumor progression and resistance to treatment. However, the ability to manipulate this pathway through physical exercise and systemic hypoxia-mediated signaling pathways could offer an important range of therapeutic opportunities that should be further investigated. This review is focused on the potential implications of systemic hypoxia combined with exercise in digestive system neoplasms prognosis. Articles included in the review were retrieved by searching among the three main scientific databases: PubMed, Scopus, and Embase. The findings of this review suggest that exercise performed under systemic hypoxic conditions could have a positive impact in prognosis and quality of life of the population with digestive system cancers. Further studies are needed to consider this paradigm as a new potential intervention in digestive oncological population.


[Improved treatment results in hilar cholangiocarcinoma after transition to more extensive procedure: 20 years experience AMC].
To determine the result of surgical treatment of patients with hilar cholangiocarcinoma (HCCA) before and after the transition from predominantly local bile duct resections to more extensive resections including partial liver resection in order to achieve complete tumour resection in the Academic Medical Center, Amsterdam (The Netherlands). Retrospective and descriptive. In the period 1988-2003, 117 consecutive patients underwent resection due to suspected HCCA. Preoperative work-up included staging laparoscopy, preoperative biliary drainage and short-course radiation therapy (3 x 3.5 Gy) to prevent seeding metastases. A more extended multidisciplinary surgical approach combining bile duct resection with partial liver resection was applied as of 1998. Outcomes of resection including 5-year survival were assessed in patients who had undergone resection before (1988-1997; period 1) and after (1998-2003; period 2) this change in surgical approach. In 18 patients (15.3%) a benign lesion was found in the resection specimen. Among the other 99 patients with microscopically confirmed HCCA, 21 (72%) of 29 patients had undergone bile duct resection in combination with partial liver resection in period 2 as compared to 17 (24%) of 70 patients in period 1. The margin tumour free resection rate increased from 20% in period 1 to 59% in period 2. Five-year survival increased from 20% (SE: 5) in period 1, to 33% (SE: 9) in period 2. Morbidity and mortality in period 2 were 69% and 10%, respectively, as compared to 64% and 17% in period 1. More extensive resection of HCCA in combination with partial liver resection in the setting of a multidisciplinary approach led to a higher rate of margin free resections and improved 5-year survival.