Binding Affinity of a Highly Sensitive Au/Ag/Au/Chitosan-Graphene Oxide Sensor Based on Direct Detection of Pb2+ and Hg2+ Ions.
The study of binding affinity is essential in surface plasmon resonance (SPR) sensing because it allows researchers to quantify the affinity between the analyte and immobilised ligands of an SPR sensor. In this study, we demonstrate the derivation of the binding affinity constant, K, for Pb2+ and Hg2+ ions according to their SPR response using a gold/silver/gold/chitosan-graphene oxide (Au/Ag/Au/CS-GO) sensor for the concentration range of 0.1-5 ppm. The higher affinity of Pb2+ to binding with the CS-GO sensor explains the outstanding sensitivity of 2.05 °ppm-1 against 1.66 °ppm-1 of Hg2+. The maximum signal-to-noise ratio (SNR) upon detection of Pb2+ is 1.53, and exceeds the suggested logical criterion of an SNR. The Au/Ag/Au/CS-GO SPR sensor also exhibits excellent repeatability in Pb2+ due to the strong bond between its functional groups and this cation. The adsorption data of Pb2+ and Hg2+ on the CS-GO sensor fits well with the Langmuir isotherm model where the affinity constant, K, of Pb2+ and Hg2+ ions is computed. The affinity of Pb2+ ions to the Au/Ag/Au/CS-GO sensor is significantly higher than that of Hg2+ based on the value of K, 7 × 10⁵ M-1 and 4 × 10⁵ M-1, respectively. The higher shift in SPR angles due to Pb2+ and Hg2+ compared to Cr3+, Cu2+ and Zn2+ ions also reveals the greater affinity of the CS-GO SPR sensor to them, thus supporting the rationale for obtaining K for these two heavy metals. This study provides a better understanding on the sensing performance of such sensors in detecting heavy metal ions.


Osseointegration of a subperiosteal anchoring device in the minipig mandible.
Onplants serve as subperiosteal anchorage in the maxilla to facilitate tooth movement. We determined the applicability of onplants and the process of osseointegration in the mandible of minipigs. Thirty-six onplants (OnPlants, Nobel Biocare USA, Yorba Linda, Calif) were positioned in 9 adult animals, 2 on each side. At 3, 6, and 12 weeks after surgery, 3 minipigs were killed. Undecalcified ground sections were evaluated histologically and histomorphometrically. Nineteen onplants were lost during the observation period. Newly formed bone per tissue volume was 7% +/- 5% (n = 4), 21% +/- 9% (n = 5), and 22% +/- 13% (n = 8) at the 3 observation times. The corresponding percentages of bone-to-implant contact were 15% +/- 22%, 30% +/- 27%, and 44% +/- 35%. The number of bone-to-implant contacts remained stable over time at 1.0 +/- 0.9 contacts per millimeter. The average lengths of bone-to-implant contacts were 0.2 +/- 0.1 mm, 0.3 +/- 0.2 mm, and 0.5 +/- 0.3 mm. These results showed a low survival rate of onplants in the mandible and that the early stage of healing is central to the process of osseointegration. Stable placement is a prerequisite for onplant survival in the mandible.


Sonographic images of hepato-pancreatico-biliary and intestinal ascariasis: A pictorial review.
Despite advancement in the diagnosis and treatment of intestinal helminthiasis, ascariasis remains the most common cause of helminthic infections in the developing countries. Ultrasound offers a rapid, safe, and noninvasive approach to the diagnosis of intestinal ascariasis. Ultrasound is also the modality of choice for diagnosis of hepatobiliary ascariasis, which is relatively rare and is due to migration of intestinal worms through the papilla of Vater. We present an imaging spectrum of hepato-pancreatico-biliary and intestinal ascariasis. • Ascariasis refer to infestation by the round worm ascaris lumbricoides. • Ascaris eggs are excreted in faeces and are infective to humans. • Eggs hatch to larva, travel to the lungs and mature to adult worms. • Intestinal obstruction can be caused by multiple ascariasis forming bag of worms.


A case of synchronous double cancers consisting of maxillary gingival carcinoma and intraductal papillary mucinous carcinoma, invasive: case report.
The development of synchronous multiple primary cancers is one of the major causes of death in patients with head and neck cancer. Herein, we report a case of synchronous intraductal papillary mucinous carcinoma (IPMC), invasive in a patient with maxillary gingival carcinoma. A 73-year-old female visited our hospital complaining of a mass on the left side of the maxillary gingiva. Intraorally, an exophytic tumor, 50 × 25 mm in size, was found on the gingiva of the left maxillary posterior, and a diagnosis of squamous cell carcinoma was revealed by cytology. Emission tomography/ computed tomography with 18 Fluorodeoxyglucose-Positron (18FDG- PET/ CT) showed increased accumulation in the left maxillary gingiva, the left side of cervical lymph nodes, and the main pancreatic duct. The pancreatic ductal tumor was performed the biopsy at esophagogastroduodenoscopy (EGD) and resulted in a pathological diagnosis of IPMC, invasive. The patient was diagnosed as synchronous double primary cancers consisting of maxillary gingival carcinoma cT4aN2bM0 and IPMC, invasive cT3N0M0. She refused radical treatment, and died 11 months later. 18FDG- PET/ CT, EGD and multidisciplinary approach is required for the detection and determining the treatment strategy of synchronous double primary cancers.


Predicting tumor deposits in patients with rectal cancer: Using the models of multiple mathematical parameters derived from diffusion-weighted imaging.
Using mono-exponential, bi-exponential, and stretched-exponential models of multi-b-value diffusion-weighted imaging (DWI) to predict tumor depositions (TDs) in patients with rectal cancer (RC). This retrospective study, between January 2018 and November 2021, enrolled 30 TDs-positive and 38 TDs-negative of patients with rectal cancer. The mathematical parameters including ADC from mono-exponential model, D, D* and f from bi-exponential model, and DDC and α from stretched-exponential model, clinical factors (such as age, gender, pathological stage, etc.) and image features (such as length, thickness, location, etc.) from tumor characteristics were obtained to identify the two groups of patients. The results were evaluated by the receiver operating characteristic curve (ROC) analysis and area under the ROC curve (AUC). Multivariate binary logistic regression analysis was conducted to determine the independent risk factors. The D* and α values, pt. stage, tumor location, mesorecta fascia (MRF) / peritoneum status and percentage of rectal wall circumference invaded (PCI) were significantly different between the TDs-positive and TDs-negative groups (P < 0.001, P < 0.001, P = 0.029, P = 0.008, P < 0.001 and P = 0.002, respectively), with the AUC were 0.838, 0.901, 0.618, 0.698 0.694 and 0.758, respectively. The D* and α values were proved to be independent risk factors after multivariate binary logistic regression analysis (p = 0.022 and 0.004, respectively). The AUC of the model consisting of the D* and α values was 0.913 (95 % CI 0.820 ∼ 0.968).The combined model constructed by D*, α and tumor location demonstrated superior diagnostic performance, with the AUC, sensitivity, specificity, and accuracy of 0.947 (95 % confidence interval, CI, 0.865-0.987), 0.900, 0.868 and 0.853, respectively. Multiple mathematical parameters can be used as preoperative auxiliary diagnostic tools to predict TDs of RC. The combined model constructed by D*, α and tumor location show better diagnostic performance for TDs.


Full recovery of right ventricular systolic function in children undergoing bilateral lung transplantation for severe PAH.
We investigated whether RV function recovers in children with pulmonary arterial hypertension (PAH) and RV failure undergoing lung transplantation (LuTx). Prospective observational study of 15 consecutive children, 1.9 to 17.6 years old, with PAH undergoing bilateral LuTx. We performed advanced echocardiography (Echo) and cardiac magnetic resonance imaging (MRI), followed by conventional and strain analysis, pre- and ∼6 weeks post-LuTx. After LuTx, RV/LV end-systolic diameter ratio (Echo), RV volumes and systolic RV function (RVEF 63 vs 30 %; p < 0.05) by MRI completely normalized, even in children with severe RV failure (RVEF < 40%). The echocardiographic end-systolic LV eccentricity index nearly normalized post-LuTx (1.0 vs 2.0, p < 0.0001) while RV hypertrophy regressed more slowly and was still evident. We found especially the end-systolic RV/LV ratios by Echo (diameter: 0.6 vs 2.6) or MRI (volumes: 0.8 vs 3.4) excellent diagnostic tools (p < 0.05): Together with RVEF by MRI, these ratios were superior to tricuspid annular plane systolic excursion (TAPSE; p = 0.4551) in assessing global systolic RV dysfunction. Moreover, children with severe PAH had reduced RV 2D longitudinal strain (Echo, MRI; p = 0.0450) and decreased RV 2D radial and circumferential strain (MRI; p = 0.0026 and p = 0.0036 respectively), all of which greatly improved following LuTx. We demonstrate full recovery of RV systolic function in children within two months after LuTx for severe PAH, independently of the patients' age, weight, and hemodynamic compromise preceding the LuTx. Even in end-stage pediatric PAH with poor RV function and low cardiac output, LuTx should be preferred over heart-lung transplantation.


Posterior tension band plate osteosynthesis for unstable sacral fractures: A preliminary study.
Stable reduction and rigid fixation of the sacrum and posterior ring structures are of paramount importance in the management of complex pelvic ring disruptions, Tile B and C. The major concern with the use of conventional methods, like iliosacral screws and iliolumbar fixations is the increased risk for surgical and implant-related morbidity, especially in difficult situations, such as comminuted, bilateral sacral fractures, and fractures in the dysmorphic sacrum. Although various biomechanical studies have reported the posterior trans-iliac plates to provide maximum resistance to distracting forces by the principle of tension band, the literature pertaining to this implication in clinical studies has been limited. The purpose of our study was to assess the efficacy of the trans-iliac plate in the management of unstable sacral fractures and its utility in pelvic disruptions associated with surgical site morbidity. The patients with unstable pelvic fractures (Tile B and C) between 2013 and 2017 were retrospectively analyzed at a trauma center. First, the anterior ring disruptions were stabilized, and then, the sacral fractures (Denis Zone 1-3) treated by posterior tension band plate osteosynthesis (3.5 mm reconstruction plate) were included. Demographic and perioperative data were assessed. The outcome variables studied were surgical morbidity, pain, loss of reduction, and union and implant-related complications. The outcomes were graded using Lindhal's (radiological) and Majeed (functional assessment) scores. Thirteen patients (nine male/four female) with a median age of 42 years, had sacral fractures in Denis zones 1/2/3 (four/ten/one, respectively), resulting from Tile pelvic injury B and C were included. The pelvis in five patients was stabilized only with the posterior plate due to the anteriorly-associated surgical site morbidity (Morel-Lavallee lesions and urinary tract injuries). The mean follow-up was 21.5 ± 2.8 months. All fractures had a radiological union by 22 weeks; Lindhal's grade A in ten patients and grade B in three patients. Two out of three patients recovered from preoperative neurological involvement. Two had complained of implant prominence (BMI<19 kg/m2) and there were no implant failures. Four had excellent, six had good, and three had fair or poor functional outcomes. The posterior trans-iliac plate is a minimally invasive and safe procedure that can be used in a wide range of unstable sacral fractures with notably less implant failure rate. The rigid posterior construct restores the principle tension between the iliac blades and minimizes the secondary displacement of the anterior disrupted structures, thereby useful in managing ring disruptions with surgical site morbidity.


The Transcription Regulator YgeK Affects Biofilm Formation and Environmental Stress Resistance in Avian Pathogenic Escherichia coli.
Avian pathogenic Escherichia coli (APEC) is one of the most common pathogens in poultry and a potential gene source of human extraintestinal pathogenic E. coli (ExPEC), leading to serious economic losses in the poultry industry and public health concerns. Exploring the pathogenic mechanisms underpinning APEC and the identification of new targets for disease prevention and treatment are warranted. YgeK is a transcriptional regulator in APEC and is localized to the type III secretion system 2 of E. coli. In our previous work, the transcription factor ygeK significantly affected APEC flagella formation, bacterial motility, serum sensitivity, adhesion, and virulence. To further explore ygeK functions, we evaluated its influence on APEC biofilm formation and resistance to environmental stress. Our results showed that ygeK inactivation decreased biofilm formation and reduced bacterial resistance to environmental stresses, including acid and oxidative stress. In addition, the multi-level regulation of ygeK in APEC was analyzed using proteomics, and associations between differentially expressed proteins and the key targets of ygeK were investigated. Overall, we identified ygeK's new function in APEC. These have led us to better understand the transcriptional regulatory ygeK and provide new clues about the pathogenicity of APEC.


Blood pressure differences between patients with lacunar and nonlacunar infarcts.
Elevated blood pressure is frequently seen in acute stroke, and patients with lacunar and nonlacunar infarcts may have different underlying mechanisms for increase in blood pressure. The impact of hypertension as a risk factor may also vary. The aims of the present study were to investigate blood pressure in patients presenting with lacunar syndromes but with different anatomical subtypes of stroke, to explore the impact of subtype on blood pressure, and to identify stroke-related factors associated with hypertension. Consecutive patients presenting with an acute lacunar syndrome were enrolled. Patients were classified into a lacunar or nonlacunar group based on radiological verified infarcts. Blood pressure was measured. Between-group differences were analyzed by χ2-test, t-test, and Mann-Whitney U test, as appropriate. We performed linear regression to analyze the association between blood pressure and lacunar infarct, and multiple linear regression to adjust for other covariates. One hundred thirteen patients were included. Seventy five percent had lacunar and 25% nonlacunar infarcts. There was no significant difference in clinical severity between the two groups. In the linear regression model, we found a significant association between blood pressure and lacunar infarct. No other factor was significantly associated with blood pressure in the two groups. Lacunar infarcts may be independently associated with higher blood pressure compared to nonlacunar infarcts with the same clinical severity. Blood pressure differences between different subtypes of stroke may not be related to clinical severity but to the underlying cause of stroke.


Readers' panel - Should school nurses be made responsible for sex education?
Our experts consider a hot topic of the day.


Prediction of successful trial of labor after cesarean among grand-multiparous women.
To determine the factors associated with successful trial of labor after cesarean (TOLAC) among grand-multiparous (GMP) women. A retrospective cohort study was conducted, including all GMP women (≥ 5 deliveries) undergoing TOLAC during 3/2011 and 6/2020, delivering a singleton cephalic newborn. Factors associated with successful vaginal delivery were examined by multivariable analysis. Overall, 381/413 (92.2%) GMP succeeded TOLAC. Maternal characteristics did not differ between TOLAC success and TOLAC failure groups. Previous cesarean delivery characteristics did not differ between study groups. The median number of previous vaginal births after cesarean was 2 [interquartile range 1-4]. Gestational age at TOLAC was lower in the success group (mean 371/7 ± 36/7 vs. 385/7 ± 31/7 weeks, p = 0.028). A lower rate of modified Bishop score < 4 was associated with TOLAC success [149 (39.1%) vs. 22 (69%), odds ratio (OR) 95% confidence interval (CI) 0.29 (0.13-0.64), p = 0.001]. The rate of induction of labor was higher in the TOLAC failure group [120 (31.5%) vs. 17 (53%), OR 95% CI 0.40 (0.19-0.83), p = 0.013]. The rate of oxytocin administration was higher in the TOLAC failure group [94 (24.7%) vs. 15 (47%) OR (95% CI) 0.37 (0.17-0.77), p = 0.006]. The duration of rupture of membranes was negatively associated with TOLAC success. Neonatal and maternal adverse outcomes did not differ between study groups. In multivariable logistic regression analysis, only the duration of rupture of membranes and modified Bishop score < 4 were independently associated with TOLAC success [adjusted OR (95% CI) 0.98 (0.96-0.99), p = 0.027 and 0.40 (0.16-0.97), p = 0.044]. TOLAC among GMP has a very-high success rate. Shortening the duration of ruptured membranes is a modifiable factor that may be associated with increased TOLAC success rates.


Abdominal surgery increases activity in several phoenixin immunoreactive nuclei.
Research on the peptide phoenixin has increased in recent years and greatly widened the known scope of its functions since its discovery in 2013. Involvement of phoenixin has since been shown in anxiety, food intake, reproduction as well as emotional and immunological stress. To further evaluate its involvement in stress reactions, this study aims to investigate the effects of abdominal surgery, a well-established physical stressor, on the activity of phoenixin-immunoreactive brain nuclei. Male Sprague-Dawley rats (n = 6/group) were subjected to either an abdominal surgery stress protocol or a sham operation. Animals in the verum group were anesthetized, the abdominal cavity opened and the cecum palpated, followed by closing of the abdomen and recovery. Sham operated animals only received inhalation anesthesia and time for recovery. All animals were subsequently sacrificed and brains processed and evaluated for c-Fos activity as well as phoenixin density. Compared to control, abdominal surgery significantly increased c-Fos activity in the paraventricular nucleus (PVN, 6.4-fold, p < 0.001), the medial part of the nucleus of the solitary tract (mNTS, 3.8-fold, p < 0.001), raphe pallidus (RPa, 3.6-fold, p < 0.001), supraoptic nucleus (SON, 3.2-fold, p < 0.001), ventrolateral medulla (VLM, also called A1C1, 3.0-fold, p < 0.001), dorsal motor nucleus of vagus (DMN, 2.9-fold, p < 0.001), locus coeruleus (LC, 1.8-fold, p < 0.01) and Edinger-Westphal nucleus (EW, 1.6-fold, p < 0.05), while not significantly altering c-Fos activity in the amygdala (CeM, 1.3-fold, p > 0.05). Phoenixin immunoreactivity was not significantly affected by abdominal surgery (p > 0.05). The observed abdominal surgery-related increase in activity in phoenixin immunoreactive nuclei compared to sham surgery controls supports the hypothesis of an involvement of phoenixin in stress reactions. Interestingly, various psychological and physical stressors lead to specific changes in activity and immunoreactivity in phoenixin-containing nuclei, giving rise to a stressor-specific involvement of phoenixin.


Simulation studies of ammonia removal from water in a membrane contactor under liquid-liquid extraction mode.
Simulation studies were carried out, in an unsteady state, for the removal of ammonia from water via a membrane contactor. The contactor had an aqueous solution of NH(3) in the lumen and sulphuric acid in the shell side. The model equations were developed considering radial and axial diffusion and convection in the lumen. The partial differential equations were converted by the finite difference technique into a series of stiff ordinary differential equations w.r.t. time and solved using MATLAB. Excellent agreement was observed between the simulation results and experimental data (from the literature) for a contactor of 75 fibres. Excellent agreement was also observed between the simulation results and laboratory-generated data from a contactor containing 10,200 fibres. Our model is more suitable than the plug-flow model for designing the operation of the membrane contactor. The plug-flow model over-predicts the fractional removal of ammonia and was observed to be limited when designing longer contactors.


Exposure to novel parainfluenza virus and clinical relevance in 2 bottlenose dolphin (Tursiops truncatus) populations.
Parainfluenza virus (PIV) is a leading cause of respiratory infections in humans. A novel virus closely related to human and bovine parainfluenza viruses types 3 (HPIV-3 and BPIV-3), named Tursiops truncatus parainfluenza virus type 1 (TtPIV-1), was isolated from a dolphin with respiratory disease. We developed a dolphin-specific ELISA to measure acute- and convalescent-phase PIV antibodies in dolphins during 1999-2006 with hemograms similar to that of the positive control. PIV seroconversion occurred concurrently with an abnormal hemogram in 22 animals, of which 7 (31.8%) had respiratory signs. Seroprevalence surveys were conducted on 114 healthy bottlenose dolphins in Florida and California. When the most conservative interpretation of positive was used, 11.4% of healthy dolphins were antibody positive, 29.8% were negative, and 58.8% were inconclusive. PIV appears to be a common marine mammal virus that may be of human health interest because of the similarity of TtPIV-1 to BPIV-3 and HPIV-3.


PAX3 expression in primary melanomas and nevi.
Melanoma is responsible for an estimated 62,000 new American cancer diagnoses and is projected to cause nearly 8000 deaths in 2008 alone. Although the histogenesis of the tumor is not well understood, it is thought to originate from a rare melanocyte stem cell that resides in the skin. The transcription factor PAX3 has a well-established role in the development of melanocytes during embryogenesis, and has recently been characterized as a molecular switch in the mature melanocyte. Based on this function, PAX3 promotes a melanocytic phenotype but blocks terminal differentiation. This mechanism may also contribute to the uncontrolled cell growth and loss of terminal differentiation in melanomas. Here, we find PAX3 expression in 8/8 melanoma cell lines. We also find that PAX3 is commonly expressed in primary melanoma samples (21/58) but significantly less frequently in benign pigmented lesions (9/75). Further analysis of our melanoma set revealed that PAX3 expression is strongly correlated with younger patients with low or no evidence of sun damage. Our data suggest that PAX3-expressing melanomas may be less environmentally dependent and more genetically linked.


Well and intermediate differentiated laryngeal chondrosarcoma: toward conservative surgery?
Chondrosarcoma of the larynx is a relatively rare malignant tumor. In the world literature, only 600 cases of laryngeal chondrosarcoma (LCS) have been reported. It is the most frequent non-epithelial tumor of the larynx (0.07-2% of all cancers), usually occurring on the cricoid. We present six cases of well-intermediate differentiated grade chondrosarcoma of the larynx, diagnosed between the fifth and seventh decades of life, in the absence of relevant risk factors. All cases were subjected to a conservative surgical approach, either endoscopic using remodeling transoral laser surgery, or open neck via a supratracheal partial laryngectomy (STL), sparing laryngeal function. All patients are free from recurrence with a minimum follow-up of 31 months. All were ultimately decannulated, are able to tolerate a quite normal diet and to speak satisfactorily. Conservative laryngeal surgery is effective because chondrosarcoma is often a low-grade tumor showing slow growth. The criteria for choosing the type of surgery was based on the age of the patient (elderly patient > favoring an endoscopic approach), on the rate of involvement of the cricoid and on the involvement of the cricoarytenoid joints (if possible to save a cricoarytenoid unit > favoring a STL). By extending the inferior limit of the resection to include a large part of the cricoid cartilage, supratracheal partial laryngectomies expanded the indications to some LCSs not involving the entire cricoid lamina sparing laryngeal function and avoiding the need for total laryngectomy.


Facilitation of motor evoked potentials (MEPs) in first dorsal interosseous (FDI) muscle is dependent on different motor images.
We investigated changes in motor evoked potentials (MEPs) to explain why mental practice can improve motor performance. MEPs were recorded from right and left first dorsal interosseous (FDI) muscles of 9 normal, right-handed subjects during different motor images of index finger movement: (1) rest, (2) flexion, (3) abduction, (4) extension. A paired t test was used to compare differences of stimulus intensities and MEP amplitudes among conditions. MEP amplitudes significantly increased in both FDI muscles during motor images of flexion and abduction but not of extension. Moreover, MEP amplitudes were larger in flexion than in abduction. These differences were proportional to the amount of real EMG discharge of FDI muscle in the selected direction of index finger movement. With regard to right-left differences, MEP amplitudes in the right FDI muscle were larger than those in the left. The primary motor cortex plays a role in the mental representation of motor acts. Furthermore, the amount of corticomotoneuronal cell activity is affected by the different motor images utilizing the same muscle. Right-left difference of MEP amplitude supports the view of left-hemisphere dominance for motor programming as an aspect of normal brain function among right-handers.


Monoclonal anti-allotype antibody towards BALB/c IgM. Analysis of specificity and site of a V-C crossover in recombinant strain BALB-Igh-Va/Igh-Cb.
Polyclonal IgM obtained by fractionation of a BALB/c serum pool was used as the immunogen for C57BL/6 mice. Draining lymph nodes from selected animals donated cells for fusion with myeloma Sp-2/0. Fifteen hybridomas were productive, and one (RS-3.1) was cloned and the affinity-purified product analyzed for its reactivity pattern by MOPC 104E-enzyme-linked immunosorbent assay inhibition. Among five BALB/c myelomas only TEPC 183 (IgM) was active, not those belonging to other Ig classes. Among normal sera from 8 mouse strains only those of BALB/c, DBA/2J and CBA/J showed inhibition. The recombinant strain BALB-Igh-Va/Igh-Cb did not react, which shows that its C mu stems from parental strain C57BL/6, and that therefore the recombination event had occurred 5' of this gene.


Tepoxalin, a novel immunomodulatory compound, synergizes with CsA in suppression of graft-versus-host reaction and allogeneic skin graft rejection.
Tepoxalin, a dual 5-lipoxygenase and cyclooxygenase inhibitor with nonsteroidal antiinflammatory effects, has recently been shown to suppress NF kappa B transactivation and inhibit T cell proliferation via a mechanism very different from cyclosporine (CsA). In this report, we demonstrate that this novel immunosuppressive effect of tepoxalin is manifested in in vivo transplantation models. Tepoxalin suppressed murine spleen cell proliferation in a mixed lymphocyte reaction (MLR) with an IC50 of 1.3 microM. Coadministration of tepoxalin and CsA in MLR cultures showed an additive inhibitory effect. Oral administration of tepoxalin at 12 mg/kg/day to mice suppressed local graft-versus-host (GVH) responses by about 40% (n = 10). Combination of tepoxalin and CsA at suboptimal doses synergized their immunosuppressive effects on GVH responses (n = 20). In skin transplantation, the median survival time of allogeneic BALB/cByJ (H-2d) mouse skin grafted onto C3H/HeJ (H-2 kappa) mice was 10.5 days (n = 8), and was prolonged to 15.0 days (n = 9) for recipient mice administered tepoxalin at 50 mg/kg/day. Coadministration of suboptimal doses of tepoxalin (12.5 mg/kg/day) and CsA (50 mg/kg/day) prolonged skin graft rejections dramatically (55% of the grafts survived for more than 40 days, n = 9). Taken together, these results demonstrate that tepoxalin is a potent immunomodulatory compound that, when combined with CsA, provides synergistic immunosuppressive activity. The fact that tepoxalin and CsA act on different transcription factors, NF kappa B and NFAT respectively, might explain the synergistic suppressive effects when both compounds were used. Tepoxalin could be an important addition to the cohort of immunosuppressive therapies currently used in solid organ and bone marrow transplantations.


Estimating time-dependent contact: a multi-strain epidemiological model of SARS-CoV-2 on the island of Ireland.
Mathematical modelling plays a key role in understanding and predicting the epidemiological dynamics of infectious diseases. We construct a flexible discrete-time model that incorporates multiple viral strains with different transmissibilities to estimate the changing patterns of human contact that generates new infections. Using a Bayesian approach, we fit the model to longitudinal data on hospitalisation with COVID-19 from the Republic of Ireland and Northern Ireland during the first year of the pandemic. We describe the estimated change in human contact in the context of government-mandated non-pharmaceutical interventions in the two jurisdictions on the island of Ireland. We take advantage of the fitted model to conduct counterfactual analyses exploring the impact of lockdown timing and introducing a novel, more transmissible variant. We found substantial differences in human contact between the two jurisdictions during periods of varied restriction easing and December holidays. Our counterfactual analyses reveal that implementing lockdowns earlier would have decreased subsequent hospitalisation substantially in most, but not all cases, and that an introduction of a more transmissible variant - without necessarily being more severe - can cause a large impact on the health care burden.


Join the green team: Inducers of plant immunity in the plant disease sustainable control toolbox.
Crops are constantly attacked by various pathogens. These pathogenic microorganisms, such as fungi, oomycetes, bacteria, viruses, and nematodes, threaten global food security by causing detrimental crop diseases that generate tremendous quality and yield losses worldwide. Chemical pesticides have undoubtedly reduced crop damage; however, in addition to increasing the cost of agricultural production, the extensive use of chemical pesticides comes with environmental and social costs. Therefore, it is necessary to vigorously develop sustainable disease prevention and control strategies to promote the transition from traditional chemical control to modern green technologies. Plants possess sophisticated and efficient defense mechanisms against a wide range of pathogens naturally. Immune induction technology based on plant immunity inducers can prime plant defense mechanisms and greatly decrease the occurrence and severity of plant diseases. Reducing the use of agrochemicals is an effective way to minimize environmental pollution and promote agricultural safety. The purpose of this workis to offer valuable insights into the current understanding and future research perspectives of plant immunity inducers and their uses in plant disease control, ecological and environmental protection, and sustainable development of agriculture. In this work, we have introduced the concepts of sustainable and environment-friendly concepts of green disease prevention and control technologies based on plant immunity inducers. This article comprehensively summarizes these recent advances, emphasizes the importance of sustainable disease prevention and control technologies for food security, and highlights the diverse functions of plant immunity inducers-mediated disease resistance. The challenges encountered in the potential applications of plant immunity inducers and future research orientation are also discussed.


Dermatological and respiratory problems in migrant construction workers of Udupi, Karnataka.
India being a developing country has tremendous demand of physical infrastructure and construction work as a result there is a raising demand of construction workers. Workers in construction industry are mainly migratory and employed on contract or subcontract basis. These workers face temporary relationship between employer and employee, uncertainty in working hours, contracting and subcontracting system, lack of basic continuous employment, lack basic amenities, and inadequacy in welfare schemes. To estimate the prevalence of respiratory and dermatological symptoms among migratory construction workers. This cross-sectional study was conducted in Manipal, Karnataka, among 340 male migratory construction workers. A standard modified questionnaire was used as a tool by the interviewer and the physical examination of the workers was done by a physician. The statistical analysis was done using Statistical Package for the Social Sciences (SPSS) version 15.0. Eighty percent of the workers belong to the age group of 18-30 years. The mean age of the workers was 26 ± 8.2 years. Most (43.8%) of the workers are from West Bengal followed by those from Bihar and Jharkhand. The rates of prevalence of respiratory and dermatological symptoms were 33.2% and 36.2%, respectively. The migrant construction workers suffer from a high proportion of respiratory and dermatological problems.


Topical 5-aminolevulinic acid with intense pulsed light versus intense pulsed light for photodamage in Chinese patients.
It has been suggested that the adjunctive use of 5-aminolevulinic acid (ALA) with intense pulsed light (IPL), known as ALA-IPL photodynamic therapy (PDT), increases the benefits of IPL therapy for photoaging. To evaluate the efficacy and safety of ALA-IPL PDT for photoaging in Chinese subjects with Fitzpatrick skin types III and IV. This was a prospective, controlled, split-face study with 26 subjects. Subjects received three split-face treatments 4 weeks apart. A blinded investigator assessed the signs of photodamage. Satisfaction was also assessed. Twenty-four subjects completed the trial. Better results were achieved for global score, fine lines, and coarse wrinkles on the PDT/IPL treated side than on the IPL-only side at the final visit (50% vs 12.5%p=.005 for global score, 70.8% vs 33.3%p=.009 for fine lines, 50% vs. 12.5%, p=.005 for coarse wrinkles). Phototoxic reactions such as erythema and edema were the primary side effects, as well as an increase in postinflammatory hyperpigmentation. ALA-IPL PDT has superior rejuvenation effects over IPL alone in Chinese subjects. Taking reasonable precaution to prevent the postinflammatory hyperpigmentation is the most important point in making ALA-IPL PDT a successful therapy.


Rapid screening of guar gum using portable Raman spectral identification methods.
Guar gum is a well-known inactive ingredient (excipient) used in a variety of oral pharmaceutical dosage forms as a thickener and stabilizer of suspensions and as a binder of powders. It is also widely used as a food ingredient in which case alternatives with similar properties, including chemically similar gums, are readily available. Recent supply shortages and price fluctuations have caused guar gum to come under increasing scrutiny for possible adulteration by substitution of cheaper alternatives. One way that the U.S. FDA is attempting to screen pharmaceutical ingredients at risk for adulteration or substitution is through field-deployable spectroscopic screening. Here we report a comprehensive approach to evaluate two field-deployable Raman methods--spectral correlation and principal component analysis--to differentiate guar gum from other gums. We report a comparison of the sensitivity of the spectroscopic screening methods with current compendial identification tests. The ability of the spectroscopic methods to perform unambiguous identification of guar gum compared to other gums makes them an enhanced surveillance alternative to the current compendial identification tests, which are largely subjective in nature. Our findings indicate that Raman spectral identification methods perform better than compendial identification methods and are able to distinguish guar gum from other gums with 100% accuracy for samples tested by spectral correlation and principal component analysis.


ESPEN guideline on chronic intestinal failure in adults - Update 2023.
In 2016, ESPEN published the guideline for Chronic Intestinal Failure (CIF) in adults. An updated version of ESPEN guidelines on CIF due to benign disease in adults was devised in order to incorporate new evidence since the publication of the previous ESPEN guidelines. The grading system of the Scottish Intercollegiate Guidelines Network (SIGN) was used to grade the literature. Recommendations were graded according to the levels of evidence available as A (strong), B (conditional), 0 (weak) and Good practice points (GPP). The recommendations of the 2016 guideline (graded using the GRADE system) which were still valid, because no studies supporting an update were retrieved, were reworded and re-graded accordingly. The recommendations of the 2016 guideline were reviewed, particularly focusing on definitions, and new chapters were included to devise recommendations on IF centers, chronic enterocutaneous fistulas, costs of IF, caring for CIF patients during pregnancy, transition of patients from pediatric to adult centers. The new guideline consist of 149 recommendations and 16 statements which were voted for consensus by ESPEN members, online in July 2022 and at conference during the annual Congress in September 2022. The Grade of recommendation is GPP for 96 (64.4%) of the recommendations, 0 for 29 (19.5%), B for 19 (12.7%), and A for only five (3.4%). The grade of consensus is "strong consensus" for 148 (99.3%) and "consensus" for one (0.7%) recommendation. The grade of consensus for the statements is "strong consensus" for 14 (87.5%) and "consensus" for two (12.5%). It is confirmed that CIF management requires complex technologies, multidisciplinary and multiprofessional activity, and expertise to care for the underlying gastrointestinal disease and to provide HPN support. Most of the recommendations were graded as GPP, but almost all received a strong consensus.


Coexistence of Copper in the Iron-Rich Particles of Aceruloplasminemia Brain.
The interaction between iron and copper has been discussed in association with human health and diseases for many years. Ceruloplasmin, a multi-copper oxidase, is mainly involved in iron metabolism and its genetic defect, aceruloplasminemia (ACP), shows neurological disorders and diabetes associated with excessive iron accumulation, but little is known about the state of copper in the brain. Here, we investigated localization of these metals in the brains of three patients with ACP using electron microscopes equipped with an energy-dispersive x-ray analyzer. Histochemically, iron deposition was observed mainly in the basal ganglia and dentate nucleus, and to lesser degree in the cerebral cortex of the patients, whereas copper grains were not detected. X-ray microanalysis identified two types of iron-rich particles in their brains: dense bodies, namely hemosiderins, and their aggregated inclusions. A small number of hemosiderins and most inclusions contained a significant amount of copper which was enough for distinct Cu x-ray images. These copper-containing particles were observed more frequently in the putamen and dentate nucleus than the cerebral cortex. Coexistence of iron and copper was supported by good correlations in the molecular ratios between these two metals in iron-rich particles with Cu x-ray image. Iron-dependent copper accumulation in iron-rich particles may suggest that copper recycling is enhanced to meet the increased requirement of cuproproteins in iron overload brain. In conclusion, the iron-rich particles with Cu x-ray image were found in the ACP brain.


Notes on public protection against hazards and nuisances: the Israeli experience.
Scientific, detailed regulations for the abatement of noise, odour and air pollutants did not prove very successful; Israel reverted to the Subjective norm of 'disturbing'. Courts proved more adaptive to change than legislators, and made use of those regulations to shift the onus of proof in keeping balance between sanity and development.


Prognostic factors for perioperative pulmonary events among patients undergoing upper abdominal surgery.
The significant relationship between upper abdominal surgery and early (perioperative) pulmonary events was investigated among patients with preoperative pulmonary conditions undergoing general anesthesia. Retrospective study for which data were obtained prospectively from 1999 to 2004, at a tertiary university hospital. We retrospectively studied 3107 patients over 11 years old presenting American Society of Anesthesiologists (ASA) status I, II or III who underwent upper abdominal surgery under general anesthesia and were discharged to the recovery room. The preoperative conditions analyzed using logistic regression were: age, sex, ASA physical status, congestive heart failure, asthma, chronic obstructive pulmonary disease (COPD), respiratory failure and smoking. The outcomes or dependent variables included intraoperative and postoperative events: bronchospasm, hypoxemia, hypercapnia, prolonged intubation and airway secretion. Among these patients (1500 males, 1607 females, mean age 48 years, 1088 ASA I, 1402 ASA II and 617 ASA III), there were 80 congestive heart failures, 82 asthmatics, 122 with COPD, 21 respiratory failures and 428 smokers. Logistic regression analysis showed that female sex (p < 0.001), age over 70 years (p < 0.01), smoking (p < 0.001) and COPD (p < 0.02) significantly influenced pulmonary event development, particularly hypoxemia and bronchospasm, at both times but not in the same patients. Asthma and congestive heart failure cases did not present pulmonary events in the recovery room. In upper abdominal surgery under general anesthesia, female sex, age over 70, smoking and COPD were independent risk factors for intra and postoperative pulmonary events.


Neuropeptide Y-like immunoreactivity in neurons of the solitary tract nuclei: vesicular localization and synaptic input from GABAergic terminals.
The ultrastructural localization of neuropeptide Y-like immunoreactivity (NPY-LI) was examined in the medial nuclei of the solitary tracts (mNTS) of adult rat brain. Peroxidase-antiperoxidase (PAP) reaction product was localized extensively to the central lumen of large (100-150 nm), dense-core vesicles. The labeled vesicles were seen in axon terminals of untreated, control animals and in perikarya and dendrites of rats receiving intraventricular injections of colchicine 24 h prior to sacrifice. The labeled terminals were of two types. The first type contained numerous small, clear vesicles that were rimmed with peroxidase product and 1-6 large, dense-core vesicles that were labeled throughout their central lumen. The second type contained a more homogeneous population of labeled large, dense-core vesicles. Axon terminals showing NPY-LI formed either asymmetric synapses with unlabeled dendrites or were without recognized junctions. Within labeled terminals, as well as within perikarya and dendrites, the majority of the dense-core vesicles were located near non-synaptic portions of the plasmalemma that were heavily ensheathed with glial processes. Only a few unlabeled terminals penetrated the glial investments to form synaptic contacts on soma or dendrites containing NPY-LI. These synaptic contacts were of both symmetric and asymmetric types. Combined immunoperoxidase labeling for glutamic acid decarboxylase and immunogold labeling for NPY further established that at least some of the terminals forming symmetric junctions on the NPY-immunoreactive dendrites were GABAergic. These results provide ultrastructural evidence that in the mNTS, NPY-LI is localized principally to large dense-vesicles within neurons whose output is partially regulated by GABA. The preferential distribution of the labeled vesicles along non-synaptic, glial-invested portions of the plasmalemma suggests that neuronal NPY may modulate the activity of nearby astrocytes. Additionally, the localization of NPY-LI in terminals containing a mixed population of synaptic vesicles and forming asymmetric axodendritic junctions suggests that NPY and/or coexisting transmitter may also exert certain known hypotensive effects by excitation of local intrinsic or projection neurons in this brain region.


Platelet-inhibitor treatment of diabetic nephropathy: a 10-year prospective study.
We prospectively evaluated a platelet-inhibitor regimen of dipyridamole and aspirin in 28 patients with insulin-dependent diabetes mellitus and well-established nephropathy. After a mean treatment period of 4.3 years, iothalamate clearance (Ciot) was reasonably well maintained and urinary protein excretion was reduced in 7 patients (25%), whereas 21 (75%) had progressive nephropathy. Analysis of outcome revealed that all 7 patients with stable nephropathy and 9 of the 21 with progressive disease had baseline Ciot values that exceeded 50 ml/min per 1.73 m2. Shortened platelet survival improved after 3 months of treatment, and the distribution between patients who had stable and those who had progressive disease was approximately equal. Mean changes in fasting plasma glucose level, glycosylated hemoglobin, and blood pressure did not differ between these two groups. In a short-term protocol, urinary protein and thromboxane B2 significantly declined, whereas variable urinary levels of prostaglandin E2, 6-ketoprostaglandin F1 alpha, and Ciot did not change after 3 months of treatment with dipyridamole and aspirin. These findings suggest that treatment with dipyridamole and aspirin may stabilize renal function by reducing platelet hypersensitivity and production of thromboxanes by platelet or renal tissue (or both). In turn, constrictor activity in the glomerular vessels, mesangial contractility, and glomerular membrane permeability are decreased. These data also add evidence in support of a role for thromboxane A2 in the pathogenesis of experimental and human glomerular disease.


JAK-inhibitors in dermatology - small molecules, big impact? Overview of the mechanism of action, previous study results and potential adverse effects.
Numerous chronic inflammatory skin diseases are associated with the release of proinflammatory cytokines, which act via the intracellular JAK-STAT pathway. JAK inhibitors represent a promising, targeted therapeutic approach for cutaneous diseases. Impressive effects have been achieved with these agents in recent years. With the approval of the JAK-inhibitors Baricitinib, Upadacitinib and Abrocitinib, new systemic therapeutic agents are now available for moderate to severe atopic dermatitis. Other diseases in which the effectiveness of these small molecules could be shown are psoriasis, chilblain lupus, dermatomyositis, vitiligo and alopecia areata. As dermatologists, we are facing a whole series of new drug approvals. In this minireview we explain the active principles of JAK inhibitors and review study results in selected inflammatory skin diseases. Finally, possible side effects and initial as well as follow-up laboratory examinations for these drugs are discussed.


Magnetic stability of SnO₂ nanosheets.
Room temperature ferromagnetism has been observed in freshly synthesized and post-annealed SnO₂ nanosheets. The results of x-ray diffraction and x-ray photoelectron spectroscopy reveal that the newly synthesized samples and those annealed at 400 °C under either an O₂ or Ar atmosphere possess rutile structure and no other impurity phases are observed. The fitting results of the O 1s and Sn 3d spectra from SnO₂ samples annealed at 400 °C under an O₂ or Ar atmosphere both indicate that oxygen vacancies inevitably exist in these samples. It is found that the saturation magnetization of all the annealed samples does not feature mono-dependence on oxygen vacancies, whereas an Sn vacancy related origin seems more plausible to account for variations in the magnetization of samples studied. This finding corresponds to first-principle calculation results from our previous work. Furthermore, the Curie temperature of SnO₂ nanosheets was estimated to be around 300 °C, rendering it a very good option for the next generation of spintronics.


[Anaphylaxis due to chicken meat].
Acute anaphylaxis due to chicken meat is very rare; only a few cases have been reported in the literature. We report the case of a 13-year-old girl, with a past history of allergic urticaria due to eggs, who presented immediately after ingestion of lightly grilled chicken meat with facial edema, dysphonia, acute dyspnoea and a feeling of suffocation. A few months later, the patient developed asthma in the vicinity of poultry and after contact with chicken feathers.


Increased expression of connective tissue growth factor in amyotrophic lateral sclerosis human spinal cord.
Connective tissue growth factor (CTGF) is a secreted protein involved in a variety of cellular events such as survival, proliferation, and extracellular matrix production. Recent studies suggest a role for this protein also in the repair processes of the central nervous system. The distribution and significance of CTGF in human brain is, however, poorly understood, particularly under pathological conditions. In the present study the expression of CTGF protein was investigated in the spinal cord of control and both sporadic and familial amyotrophic lateral sclerosis (sALS and fALS) patients. Western blot analysis showed a consistent increase in CTGF expression in six sALS patients compared with controls. Immunoreactivity signal for CTGF was equally present in blood vessels of control and ALS spinal cord, but was dramatically increased in reactive astrocytes of the ventral horn and white matter in both sALS and fALS. Increased expression was also observed in the cytoplasm of motor neurons of sALS and fALS patients with long duration of the disease. Our data indicate a role for CTGF in the complex reactive process that is associated with the progression of ALS spinal cord damage. The up-regulation in reactive astrocytes supports a role for CTGF in the molecular mechanisms underlying astrogliosis. However, the altered CTGF expression observed in neurons might represent an additional mechanism involved in motor neuron dysfunction and changes in glial-neuronal communication in the course of the neurodegenerative process.


Passive estimation of target velocity based on cross-spectrum histogram.
In underwater acoustic target parameter estimation, the cross-spectrum method estimates the velocity of the target by the interference structure of the cross-correlated fields in two ranges. However, with the increase in interference in the marine environment, the performance of conventional cross-spectrum target velocity estimation methods gradually declines or even fails. To solve this problem, a cross-spectrum histogram method that combines the multi-line spectrum characteristics of the target is proposed in this paper. First, each frequency point of all line spectra is compensated by the cross-spectrum compensation method. Then the target velocity estimation value is obtained by performing probability distribution statistics on the velocity estimation results for all frequency points. Under different signal-to-noise ratios, simulations and experiments are carried out to verify the effectiveness of the proposed method. The results show that the proposed method is still effective in estimating the target velocity when the conventional method fails.


Ambrisentan use for pulmonary arterial hypertension in a post-authorization drug registry: The VOLibris Tracking Study.
The VOLibris Tracking (VOLT) Study was an open-label, prospective, observational, multicenter, post-marketing registry program designed to more fully characterize the safety profile of ambrisentan for the treatment of pulmonary arterial hypertension (PAH). The key outcome was the incidence of aminotransferase elevations >3× the upper limit of normal (ULN). In total, 999 patients from 115 centers in 15 countries, who were prescribed ambrisentan for the treatment of PAH (Functional Class II and III) between 30 June 2008 and 13 May 2011, were enrolled. Of these, 238 had PAH associated with connective tissue disease (PAH-CTD) and 220 had no prior PAH-specific therapy. Routine clinical monitoring data were collected by physicians. The incidence of both alanine and aspartate aminotransferase events (>3× ULN) was 0.02 per patient-year (95% confidence interval 0.015 to 0.027). Similar results were reported for the PAH-CTD and PAH-specific-therapy-naive subgroups. Overall, 514 (52%) patients reported treatment-emergent adverse events of special interest, most commonly edema/fluid retention (249, or 25%) and anemia (143, or 14%). Data from the VOLT study indicate no new ambrisentan-related safety signals. Ambrisentan was not associated with increases in liver function test abnormalities above the assumed background incidence of 1.5% per year, and the observed safety profile of ambrisentan was consistent with previously published data.


Association of Biomarker-Based Treatment Strategies With Response Rates and Progression-Free Survival in Refractory Malignant Neoplasms: A Meta-analysis.
The impact of a biomarker-based (personalized) cancer treatment strategy in the setting of phase 1 clinical trials was analyzed. To compare patient outcomes in phase 1 studies that used a biomarker selection strategy with those that did not. PubMed search of phase 1 cancer drug trials (January 1, 2011, through December 31, 2013). Studies included trials that evaluated single agents, and reported efficacy end points (at least response rate [RR]). Data were extracted independently by 2 investigators. Response rate and progression-free survival (PFS) were compared for arms that used a personalized strategy (biomarker selection) vs those that did not. Overall survival was not analyzed owing to insufficient data. A total of 346 studies published in the designated 3-year time period were included in the analysis. Multivariable analysis (meta-regression and weighted multiple regression models) demonstrated that the personalized approach independently correlated with a significantly higher median RR (30.6% [95% CI, 25.0%-36.9%] vs 4.9% [95% CI, 4.2%-5.7%]; P < .001) and a longer median PFS (5.7 [95% CI, 2.6-13.8] vs 2.95 [95% CI, 2.3-3.7] months; P < .001). Targeted therapy arms that used a biomarker-based selection strategy (n = 57 trials) were associated with statistically improved RR compared with targeted therapy arms (n = 177 arms) that did not (31.1% [95% CI, 25.4%-37.4%] vs 5.1% [95% CI, 4.3%-6.0%]; P < .001). Nonpersonalized targeted arms had outcomes comparable with those that tested a cytotoxic agent (median RR, 5.1% [95% CI, 4.3%-6.0%] vs 4.7% [95% CI, 3.6%-6.2%]; P = .63; respectively; median PFS, 3.3 [95% CI, 2.6-4.0] months vs 2.5 [95% CI, 2.0-3.7] months; P = .22). Personalized arms using a "genomic (DNA) biomarker" had higher median RR than those using a "protein biomarker" (42.0% [95% CI, 33.7%-50.9%] vs 22.4% [95% CI, 15.6%-30.9%]; P = .001). The median treatment-related mortality was not statistically different for arms that used a personalized strategy vs not (1.89% [95% CI, 1.36%-2.61%] vs 2.27% [95% CI, 1.97%-2.62%]; P = .31). In this meta-analysis, most phase 1 trials of targeted agents did not use a biomarker-based selection strategy. However, use of a biomarker-based approach was associated with significantly improved outcomes (RR and PFS). Response rates were significantly higher with genomic vs protein biomarkers. Studies that used targeted agents without a biomarker had negligible response rates.


Chemical Composition and Anti-Nutritional Profiling of Wattle (Acacia cyclops, Acacia microbotrya and Acacia victoriae) Seed Originating from Western Australia.
The chemical and anti-nutritional, antioxidative and anti-microbial properties of seeds from Acacia cyclops, Acacia microbotrya and Acacia victoriae(which are legumes) traditionally consumed by indigenous Western Australians were studied for the first time for their potential as commercial food components. A. microbotrya (2.7 CIU/g) (α < 0.05) had the highest α-chymotrypsin inhibitor activity, while A. victoriae (0.3 ± 0.03) had the highest trypsin inhibitor activity. Both A. microbotrya (0.2 ± 0.02) and A. victoriae (0.2 ± 0.08) had significantly higher oxalate content than A. cyclops. The anti-microbial properties of wattle seed extracts against the foodborne pathogens Bacillus cereus, Escherichia coli, Salmonella Typhimurium and Staphylococcus aureus were determined. A. cyclops demonstrated the greatest anti-microbial activity against all the microorganisms studied. A. microbotrya had significantly higher amounts of protein (27.2%), fat (3.4%), fibre (49.2 mg/100 g), iron (5.2 mg/100 g), potassium (1275.5 mg/100 g) and zinc (3.8 mg/100 g) than the other two Acacia species. A. victoriae had the highest DPPH equivalent antioxidant activity (37.1%). The wattle seeds studied are higher in protein, dietary fiber, zinc and potassium compared to some commonly consumed legumes such as lentils and chickpeas. Incorporation of wattle seed in to food may provide additional health benefits to consumers. Their ability to inhibit foodborne bacteria means they may have potential as a natural food additive.


Postural adjustments in preterm infants at 4 and 6 months post-term during voluntary reaching in supine position.
Gradually it is getting clear that motor development - in particular balance control - in so-called "low-risk" preterm infants often differs from that in full-term infants. However, little is known on the etiology and pathophysiology of these problems. The aim of this study was to evaluate postural behavior during reaching by means of kinetic and kinematic measurements. Preterm infants (n = 32) without cerebral palsy were investigated longitudinally at the corrected ages of 4 and 6 mo. Thirteen age-matched full-term infants served as controls. Cognitive and motor development were assessed by means of the quality of General Movements (GMs) at 4 mo and Bayley scales at 6 and 12 mo. The infants were lying supine on a forceplate reaching for a toy and the kinetics of the total body's Center of Pressure (COP) was measured in cranial-caudal and medial-lateral direction. The analysis focused on COP displacement, Vmax and oscillatory changes of the COP displacement during reaching. The kinematic analysis of reaching focused on movement units, Vmax and a compound kinematic variable reflecting the quality of reaching. The results showed that preterm infants showed a remarkable "still" postural behavior, which differed significantly from the mobile COP behavior of the full-term infants. More "still" postural behavior at 6 mo was associated with a better quality of reaching movements and with normal GMs at 4 mo. We concluded that "still" postural behavior is an adequate postural strategy of preterm infants. But it might be that this postural behavior is an indicator of later dysfunction.


The Australian Incident Monitoring Study: an analysis of 2000 incident reports.
The Australian Patient Safety Foundation was formed in 1987; it was decided to set up and co-ordinate the Australian Incident Monitoring Study as a function of this Foundation; 90 hospitals and practices joined the study. Participating anaesthetists were invited to report, on an anonymous and voluntary basis, any unintended incident which reduced, or could have reduced, the safety margin for a patient. Any incident could be reported, not only those which were deemed "preventable" or were thought to involve human error. The Mark I AIMS form was developed which incorporated features and concepts from several other studies. All the incidents in this symposium were reported using this form, which contains general instructions to the reporter, key words and space for a narrative of the incident, structured sections for what happened (with subsections for circuitry incidents, circuitry involved, equipment involved, pharmacological incidents and airway incidents), why it happened (with subsections for factors contributing to the incident, factors minimising the incident and suggested corrective strategies), the type of anaesthesia and procedure, monitors in use, when and where the incident happened, the experience of the personnel involved, patient age and a classification of patient outcome. Enrollment, reporting and data-handling procedures are described. Data on patient outcome are presented; this is correlated with the stages at which the incident occurred and with the ASA status of the patients. The locations at which the incidents occurred and the types of procedures, the sets of incidents analysed in detail and a breakdown of the incidents due to drugs are also presented.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of aculeacin A on reverting protoplasts of Candida albicans.
Protoplasts of Candida albicans were prepared by digestion with Zymolyase and the effect of aculeacin A, a wall-active antibiotic, on the synthesis of microfibrillar structures by the protoplasts incubated for 5 hr in an osmotically stabilized medium was studied using several electron microscopical techniques. Chemical analyses of the protoplasts before and after reversion with or without the antibiotic were also performed. Aculeacin A not only inhibited synthesis of microfibrils mainly composed of alkali-insoluble beta-glucan, but also their assembly to form thicker bundles. The antibiotic appeared to have no effect on other wall components constituting the surface structure of reverting protoplasts. These data confirmed our previous postulation that aculeacin A is a specific and potent inhibitor of beta-glucan synthesis as well as biogenesis of cell walls including beta-glucans in susceptible yeasts.


Does moderate mitral regurgitation impact early or mid-term clinical outcome in patients undergoing isolated aortic valve replacement for aortic stenosis?
The early and mid-term impact of functional mitral regurgitation (MR) in patients undergoing isolated aortic valve replacement (AVR) for aortic stenosis remains unresolved. Through our institutional databank, using a case-match study, we identified 58 patients with MR grades 0-1 and 58 patients with MR grades 2-3 (patients matched for sex, age, ejection fraction (EF), NYHA, diabetes, and CVA). Data were collected prospectively (mean duration of follow-up: 3.2 +/- 2.4 years). Perioperative morbidity (re-operation for bleeding, low cardiac output, CVA, renal failure) was comparable among groups. Difference in mortality between the two groups was non-significant (7.0 vs. 3.5%, P = 0.67 in groups MR 2-3 vs. 0-1, respectively). At early echocardiographic follow-up, 7/58 patients (12.1%) within group MR grades 0-1 increased their MR to grades 2-3; among which only two remained with MR grades 2-3 at mid-term follow-up. Within MR group 2-3, 18/58 (31.0%) remained with MR grades 2-3 among which 7/18 (38.9%) decreased of at least one grade at follow-up. Eight year actuarial survival was comparable in both groups: MR grades 0-1 = 60.9% vs. MR grades 2-3 = 55.0%; P = 0.1. Actuarial survival of patients with MR grades 2-3 postoperatively was similar to patients with MR grades 0-1 (MR grades 0-1 = 59.0%, MR grades 2-3 = 58.9%, P = NS). Presence of preoperative moderate functional MR (grades 2-3) in patients undergoing isolated AVR for aortic stenosis regresses in the majority of patients postoperatively and has no significant impact on perioperative morbidity or mortality, nor mid-term survival. Thus, moderate functional MR should be treated conservatively in the majority of patients especially in the elderly subjected to isolated AVR for aortic stenosis.


Rapid Kupffer cell death after intravenous injection of adenovirus vectors.
When adenovirus vectors are injected intravenously, they are quickly taken up by Kupffer cells in the liver. We report that this causes rapid necrosis of Kupffer cells in mice at doses of 10(11) particles/kg or higher. By 10 min after intravenous vector injection, Kupffer cells were permeable to propidium iodide and trypan blue. This coincided with a sharp rise in serum lactate dehydrogenase. Ultrastructural examination showed degeneration of Kupffer cells, including complete disappearance of chromatin by 1 h. After an initial intravenous injection of vector, dead Kupffer cells were unable to take up a second dose of vector, and hepatic transgene expression from the second dose was augmented. Death of Kupffer cells did not affect serum levels of IL-6 or IL-12. There was no immediate change in the number of Kupffer cells in the liver, but a significant decline was found by 4 h after injection of vector. Interestingly, substantial numbers of vector-containing Kupffer cells were found in pulmonary capillaries, indicating that they had been swept out of the liver. Together these results show that an intravenous injection of adenovirus vector causes synchronous and surprisingly rapid Kupffer cell death.


Assessment of carbon emission reduction contribution of Chinese power grid enterprises based on MCS-GA-ELM method.
To achieve China's "double carbon" goal, it is necessary to make quantitative evaluation of the power grid enterprises' contribution to carbon emission reduction. This paper analyzes the contribution of power grid enterprises to carbon emission reduction from three points: power generation side, power grid side, and user side. Then, PLS-VIP method is used to screen the key influencing factors of carbon emission reduction contribution of power grid enterprises from three aspects: consumption of clean energy emission reduction, reduction of line loss emission reduction, and substitution of electric energy. Based on GA-ELM combined machine learning algorithm, we establish an intelligent evaluation model of power grid enterprises' carbon emission reduction contribution. Furthermore, according to the distribution law of key influencing factors, this paper uses Monte Carlo simulation method to calculate the contribution of power grid enterprises to carbon emission reduction by scenario, so as to evaluate the contribution of power grid enterprises to carbon emission reduction. Finally, combined with the relevant data of power grid enterprises from 2003 to 2019, this paper makes an empirical study on the completion of carbon emission reduction contribution and the promotion path.


Zinc and the diabetic heart.
Zinc (Zn) is an essential mineral that is required for various cellular functions. Its abnormal metabolism is related to certain disorders such as diabetic complications. Oxidative stress has been considered as the major causative factor for diabetic cardiomyopathy. Zn has a critical antioxidant action in protecting the heart from various oxidative stresses. Zn deficiency was found to be a risk factor for cardiac oxidative damage and supplementation with Zn provides a significant prevention of oxidative damage to the heart. Diabetes causes a significant systemic oxidative stress and also often is accompanied by Zn deficiency that increases the susceptibility of the heart to oxidative damage. Therefore, there is a strong rationale to consider the strategy of Zn supplementation to prevent or delay diabetic cardiomyopathy. This short article collects the preliminary evidence, based on our own studies and those by others, for a preventive effect of Zn supplementation on diabetes-induced injury to the heart in animals and under in vitro conditions. Possible mechanisms by which Zn supplementation prevents diabetic heart disease are discussed. They include an antioxidant action of Zn, insulin function and metallothionein induction. In the final section, the future of Zn supplementation for diabetic patients is also briefly discussed. Although Zn supplementation has not been clinically used to prevent diabetic complications, because several issues need to be addressed, the fact that Zn supplementation is being used clinically for other disorders encourages us to explore its direct clinical application for the prevention of diabetic cardiomyopathy.


90% of fixed partial dentures survive 5 years. How long do conventional fixed partial dentures (FPDs) survive and how frequently do complications occur?
PubMed (1966-April 2004) provided the primary data source along with the bibliographies from identified articles and reviews. As there were no randomised controlled trials, English language prospective and retrospective cohort studies were selected if they had a mean follow-up of >/=5 years, included patients who were clinically examined at follow-up, reported details on suprastructures and described at least one-third of reconstructions as fixed partial dentures (FPDs). Two independent reviewers screened articles for inclusion. Disagreements were resolved by discussion and agreement determined by kappa. Three reviewers extracted data on the survival and success of the reconstructions and on biological and technical complications. Studies deemed sufficiently similar by design were pooled using negative binomial regression with robust standard errors. Ten-year survival risks were calculated using exp(-10 x failure rate) and 10-year failure risks using 1-S(10). 17 retrospective and two prospective cohort studies including 1764 patients with 3548 FPDs analyzed in total. Meta-analysis was undertaken and after exclusion of one outlier a 10-year FPD survival of 92% was estimated. Only four studies provided information on FPD success - pooled complication rate was 34.1/1000 FPD years (95% CI 16-74). Exclusion of one outlier resulted in an estimated 10-year success of 81.1%. Considering biological complications, the estimated 10-years risk for caries at abutments was 9.5% (95% CI 4.6-89.9) while that for FPD loss due to caries and periodontal disease were 2.6% (95% CI 1.6-4.2) and 0.5% (95% CI 0.1-2.2), respectively. Estimated 10-year risks for technical complications were: 6.4% (95% CI 3.9-10.4) for loss of retention; 2.1% (95% CI 1.4-3.2) for loss of FPD due to abutment fracture and 3.2% (95% CI 1.5-6.5) for material fractures. Estimated success and survival rates for conventional FPDs largely confirm those of previous reviews. Technical complications such as loss of retention, which have not been reviewed before, resulted in a greater risk of FPD loss than did biological complications.


Synthesis, Characterization, Antimicrobial Activity, and Docking Studies of New Triazolic Tripodal Ligands.
The synthesis and characterization of new N-donor bitriazolic tripods were reported. The in vitro antibacterial and antifungal activities of these products were screened against fungal strain (Candida pelliculosa) and against four bacterial strains (Micrococcus luteus, Bacillus subtilis, Listeria innocua, and Escherichia coli). Biological data revealed the effect of the chemical structure on antimicrobial activity. Molecular docking studies of some compounds showed that they could act as inhibitors for the biotin carboxylase enzyme.


Immunocytochemical localization of pepsinogen in rat stomach.
The localization of pepsinogen in rat stomachs was investigated by a postembedding immunoferritin method. When the preparations embedded in Epon were used, the secretory granules of chief cells were stained heavily and the granules of mucous neck cells were stained moderately. The secretory granules of cells intermediate between mucous neck cells and chief cells showed a bizonal staining; the electron dense parts were stained heavily and the electron lucent parts were stained moderately. The secretory granules of pyloric gland cells, on the other hand, were labeled faintly. However, the secretory granules of surface mucous cells, foveolar mucous cells, endocrine cells, cardiac mucous cells and cardiac serous cells were not stained by the method. The protein A-gold method showed a similar staining pattern of pepsinogen to that of the immunoferritin method. When the samples embedded in Lowicryl K4M were used to enhance the stainability of pepsinogen, essentially the same staining pattern as that of the samples embedded in Epon was obtained. In addition, the Golgi apparatus and the rough surfaced endoplasmic reticulum were more easily stained.


Mediating effect of behavioural intention on podcast acceptance.
This research contributes to knowledge in mediating effect of lecturers' behavioural intention towards the acceptance of podcasts technology in universities. A cross-sectional quantitative research design was involved in this study. Also, a total of eight hundred and twenty-nine (829) lecturers participated in this research from three different south-west Nigeria Federal universities. The research instrument was titled lecturer's acceptance questionnaire (LAQ) with a calculated Cronbach's alpha of .919, which confirmed the instrument validity. The gathered data was analysed by using both descriptive and inferential statistics. The formulated hypothesis was tested at .05 level of significance. The result from descriptive analysis of data suggested that behavioural intention was at a low level among lecturers and the results of hypothesis testing revealed the effect of behavioural intention as partial mediator of podcast acceptance. Based on these findings relevant conclusions and recommendations were suggested in this research.


Topical ethyl ether therapy of herpes simplex lesions.
A simple and effective method of treating herpes simplex lesions using topical application of ethyl ether relieves pain almost immediately and aborts progression of the lesion. The therapeutic rationale for using this modality is based on the ability of ether to penetrate the epidermis and to destroy the ether sensitive envelope of the virus. A decrease in frequency and even elimination of recurrences has been suggested.


Metabolic alterations of liver regeneration. XV. Cadmium-mediated depression of thymidine and thymidylate kinase induction in rats.
Cadmium administered shortly before or after partial hepatectomy blocks in a dose-dependent manner the increase of thymidine and thymidylate kinase activities in regenerating rat livers. The effect of cadmium can be partially antagonized by simultaneous zinc administration. The intraperitoneal injection of cadmium is more effective than its subcutaneous administration. While there are in vitro differences in the sensitivity of thymidine kinase and thymidylate kinase towards Cd2+-, Zn2%- and Cu2+-ions, both enzymes are equally depressed following their in vivo administration. Cadmium displays the highest inhibitory activity and resembles in this respect beryllium [1].


Barriers to addressing the social determinants of health: insights from the Canadian experience.
Despite Canada's reputation as a leader in health promotion and population health, implementation of public policies in support of the social determinants of health has been woefully inadequate. The continuing presence of income, housing, and food insecurity has led to Canada being the subject of a series of rebukes from the United Nations for failing to address child and family poverty, discrimination against women and Aboriginal groups, and most recently the crisis of homelessness and housing insecurity. In this article we consider some of the reasons why this might be the case. These include the epistemological dominance of positivist approaches to the health sciences, the ideology of individualism prevalent in North America, and the increasing influence on public policy of the marketplace. Various models of public policy provide pathways by which these barriers can be surmounted. Considering that the International Commission on the Social Determinants of Health will soon be releasing its findings and recommendations, such an analysis seems especially timely for understanding both the Canadian scene and developments in other nations.


Comprehensive quality assessment for Rhizoma Coptidis based on quantitative and qualitative metabolic profiles using high performance liquid chromatography, Fourier transform near-infrared and Fourier transform mid-infrared combined with multivariate statistical analysis.
Rhizoma Coptidis (RC) originated from the dried rhizomes of Coptis herbal species is a widely used traditional Chinese medicine in history. In this study, a comprehensive quality assessment for RC medicines from C. chinensis, C. deltoidea, C. omeiensis and C. teeta species was performed based on quantitative and qualitative metabolic profiles obtained from high performance liquid chromatography (HPLC), Fourier transform near-infrared (FT-NIR) and Fourier transform mid-infrared (FT-MIR) combined with multivariate statistical analysis. Eight alkaloids including magnoflorine, groenlandicine, jatrorrhizine, columbamine, epiberberine, coptisine, palmatine and berberine were simultaneously identified and determined. Epiberberine, berberine, magnoflorine and groenlandicine were identified as possible index components. FT-NIR and FT-MIR profiles presented the holistic metabolic characterization of RC medicines. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were successively performed to clearly illustrate the metabolic variation and taxonomic relationship among four RC medicines. Additionally, taking berberine as an example, spectral quantification potential was investigated by referring HPLC data, using a conventional partial least squares regression (PLSR) algorithm. Data fusion strategy exhibited a better prediction for this compound than a single technique. Summary, these techniques can complement each other and provide a comprehensive and effective quality assessment for RC originated from different Coptis plants.


Retention and attrition among African Americans in the STAR*D study: what causes research volunteers to stay or stray?
High attrition rates among African-Americans (AA) volunteers are a persistent problem that makes clinical trials less representative and complicates estimation of treatment outcomes. Many studies contrast AA with other ethnic/racial groups, but few compare the AA volunteers who remain in treatment with those who leave. Here, in addition to comparing patterns of attrition between African Americans and Whites, we identify predictors of overall and early attrition among African Americans. Sample comprised non-Hispanic African-American (n = 673) and White (n = 2,549) participants in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Chi-square tests were used to examine racial group differences in reasons for exit. Multivariate logistic regression was used to examine predictors of overall attrition, early attrition (by level 2) and top reasons cited for attrition among African Americans. Both African-American and White dropouts most commonly cited noncompliance reasons for attrition during the earlier phases of the study, while citing reasons related to efficacy and medication side effects later in the study. Satisfaction with treatment strongly predicted overall attrition among African Americans independent of socioeconomic, clinical, medical or psychosocial factors. Early attrition among African American dropouts was associated with less psychiatric comorbidity, and higher perceived physical functioning but greater severity of clinician-rated depression. Compliance, efficacy, and side effects are important factors that vary in relative importance during the course of a clinical trial. For African Americans in such trials, retention strategies should be broadened to emphasize patient engagement and satisfaction during the critical periods immediately following enrollment and treatment initiation.


A ribosome-associated chaperone enables substrate triage in a cotranslational protein targeting complex.
Protein biogenesis is essential in all cells and initiates when a nascent polypeptide emerges from the ribosome exit tunnel, where multiple ribosome-associated protein biogenesis factors (RPBs) direct nascent proteins to distinct fates. How distinct RPBs spatiotemporally coordinate with one another to affect accurate protein biogenesis is an emerging question. Here, we address this question by studying the role of a cotranslational chaperone, nascent polypeptide-associated complex (NAC), in regulating substrate selection by signal recognition particle (SRP), a universally conserved protein targeting machine. We show that mammalian SRP and SRP receptors (SR) are insufficient to generate the biologically required specificity for protein targeting to the endoplasmic reticulum. NAC co-binds with and remodels the conformational landscape of SRP on the ribosome to regulate its interaction kinetics with SR, thereby reducing the nonspecific targeting of signalless ribosomes and pre-emptive targeting of ribosomes with short nascent chains. Mathematical modeling demonstrates that the NAC-induced regulations of SRP activity are essential for the fidelity of cotranslational protein targeting. Our work establishes a molecular model for how NAC acts as a triage factor to prevent protein mislocalization, and demonstrates how the macromolecular crowding of RPBs at the ribosome exit site enhances the fidelity of substrate selection into individual protein biogenesis pathways.


Eyes wide shut: linking brain and pupil in bilingual and monolingual toddlers.
A new study reports interesting results concerning the way in which monolingual and bilingual toddlers cope with conflicting information regarding the names of objects. The study used a novel approach that combines electrophysiological recordings (event-related potentials) and changes in pupil size, opening new ways to explore early human development.


[Intra-articular ketamine after arthroscopic knee surgery. Optimisation of postoperative analgesia].
Surgery of the knee can be very painful and sufficient postoperative pain treatment is often problematic. To optimize postoperative analgesia, application of local analgesics has been suggested. In the present study it was investigated whether intra-articular administration of ketamine reduces the level of pain after arthroscopic knee surgery. A total of 68 patients undergoing arthroscopic knee surgery were randomized into 4 groups. At the end of surgery the following pharmaceuticals were administered: 10 ml 0.25% bupivacaine intra-articular (i.a.), 0.25 mg S-(+)-ketamine/kg body weight to 10 ml in 0.9% NaCl i.a., 0.25 mg S-(+)-ketamine/kg body weight intravenous (i.v.), and 10 ml 0.9% NaCl i.a. as placebo. Postoperative pain therapy was performed as i.v. patient controlled analgesia (PCA) with piritramide. Postoperative opioid consumption and pain intensity were assessed as the main criteria in the postoperative course. All 4 groups were comparable with respect to biometrical data. The scores of the visual analogue scale (VAS) showed a significantly (p<0.05) lower pain intensity in patients treated with ketamine i.a. or i.v. compared to the other groups. Shortly after surgery the highest reduction of pain was detected in the i.a. ketamine group compared to i.a. bupivacaine or placebo administration. The postoperative opioid consumption was always lowest in the i.a. ketamine group. A significant difference in piritramide consumption (p<0.05) was demonstrated in the first 20 min after operation in the i.a. ketamine group compared to the i.a. administration of placebo and bupivacaine. The i.a. application of ketamine after arthroscopic knee surgery leads to a significant decrease of postoperative analgesic demand and decreases patients' subjective level of pain compared to i.a. application of bupivacaine or placebo. Likewise, the i.v. application of ketamine is similarly effective but the effect is of shorter duration.


Challenges in implementing CD4 testing in resource-limited settings.
The scale-up of HIV antiretroviral therapy in recent years has led to a rapid increase in CD4 and CD4% count capacity to meet the diagnostic needs of staging and monitoring disease progression and treatment efficacy in adults and infants. The speed of implementation of this technology has been unrivalled in recent years and has met challenges with technology selection, laboratory infrastructure development, human resource limitations, cost-effectiveness, instrument maintenance, and ensuring testing access and quality. The lessons learned from dealing with these challenges have helped strengthen existing laboratory systems for other diagnostics. They may also facilitate the implementation of new diagnostics in future.


Polyvinyl alcohol enhances detection of low abundance transcripts in early stage quail embryos in a nonradioactive whole mount in situ hybridization technique.
We have tested the ability of polyvinyl alcohol (PVA) to enhance the indoxyl-nitro blue tetrazolium alkaline phosphatase color reaction in whole mount in situ hybridizations of early stage quail embryos. Using detection of the myogenic factor qmyoD in hybridizations of 13-14 somite-pair quail embryos as a test system, 10% solutions of 13-23 kDa and 31-50 kDa PVA optimally enhanced the alkaline phosphatase color reaction. With the enhanced detection conditions, we have been able to measure qmyoD expression as early as the 3 somite-pair stage, whereas previously we were unable to detect qmyoD prior to the 10 somite-pair stage. PVA-enhanced detection of somitic qmyoD expression was specific as no corresponding signal was found in control hybridizations with a sense qmyoD probe.


A new species of Isospora Schneider, 1881 (Apicomplexa: Eimeriidae) from Morafka's desert tortoise Gopherus morafkai (Testudines: Testudinidae).
Isospora gopheri n. sp. (Apicomplexa: Eimeriidae) is described from 5 of 28 (18%) Morafka's desert tortoise Gopherus morafkai Murphy, Berry, Edwards, Leviton, Lathrop & Readle, housed by the Phoenix Herpetological Society, Maricopa County, Arizona, USA. Sporulated oöcysts of this new species were spheroidal to subspheroidal, 20-27 × 19-27 (23.0 × 21.7) µm, with a smooth, bi-layered wall and 1-3 polar granules; an oöcyst residuum was absent. Sporocysts were elongate-ovoidal to ellipsoidal, 13-18 × 9-12 (15.9 × 10.2) µm, with a Stieda body, sub-Stieda body and sporocyst residuum; sporozoites were banana-shaped with an ellipsoidal posterior refractile body and a spheroidal anterior refractile body. This is both the first coccidian to be described from this host species and only the second reported from the host genus.


Ontology-based, Tissue MicroArray oriented, image centered tissue bank.
Tissue MicroArray technique is becoming increasingly important in pathology for the validation of experimental data from transcriptomic analysis. This approach produces many images which need to be properly managed, if possible with an infrastructure able to support tissue sharing between institutes. Moreover, the available frameworks oriented to Tissue MicroArray provide good storage for clinical patient, sample treatment and block construction information, but their utility is limited by the lack of data integration with biomolecular information. In this work we propose a Tissue MicroArray web oriented system to support researchers in managing bio-samples and, through the use of ontologies, enables tissue sharing aimed at the design of Tissue MicroArray experiments and results evaluation. Indeed, our system provides ontological description both for pre-analysis tissue images and for post-process analysis image results, which is crucial for information exchange. Moreover, working on well-defined terms it is then possible to query web resources for literature articles to integrate both pathology and bioinformatics data. Using this system, users associate an ontology-based description to each image uploaded into the database and also integrate results with the ontological description of biosequences identified in every tissue. Moreover, it is possible to integrate the ontological description provided by the user with a full compliant gene ontology definition, enabling statistical studies about correlation between the analyzed pathology and the most commonly related biological processes.


Inhibition of the binding of cytochrome b5 to phosphatidylcholine vesicles by cholesterol.
The binding of cytochrome b5 to single-walled liposomes of egg phosphatidylcholine was inhibited by the presence of cholesterol in the lipid bilayer under conditions where a limited amount of liposomes was incubated with the cytochrome. Since similar conditions seem to apply for the binding of cytochrome b5 to erythrocyte ghosts, this observation supports the conclusion of Enomoto and Sato (Enomoto, K. and Sato, R. (1977) Biochim. Biophys. Acta 466, 136--147) that the localization of cholesterol on the outer surface of the ghost membrane prevents the binding of cytochrome b5 to this surface. The finding reported by Roseman et al. (Roseann, M.A., Holloway, P.W. and Calabro, M.A. (1978) Biochmi. Biophys. Acta 507, 552--556) that cholesterol did not prevent the cytochrome binding to phosphatidylcholine liposomes in the presence of a large excess of liposomes could be confirmed in the present study, but this does not contradict the abovementioned conclusion.


Dr. Johnstone et al. Reply to Dr. Elmrayed.
We thank Dr. Elmrayed and colleagues1 for highlighting clinical cautions in using broad-spectrum micronutrients to treat attention-deficit/hyperactivity disorder (ADHD) in children, in particular manganese (Mn) levels. We appreciate the opportunity to provide additional information and rationale for the vitamin and mineral doses contained in the studied formula.


Association between anorexia and hyposalivation in community-dwelling older adults in Japan: a 6-year longitudinal study.
Hyposalivation is associated with the nutritional status. Anorexia of ageing, defined as an age-related decrease in appetite and food intake, presents even in healthy adults and is considered an independent predictor of malnutrition, frailty, and mortality. However, the relationship between anorexia and hyposalivation of ageing is unclear. Thus, the present longitudinal study aimed to investigate the incidence of hyposalivation and its relationship with anorexia in community-dwelling older people in Japan. The study population comprised 220 individuals (80 men and 140 women) aged 65-86 years at baseline. The participants underwent comprehensive health check-ups, including dental examinations and anthropometry, and face-to-face interviews in 2013 and 2019. Hyposalivation was determined on the basis of the unstimulated salivary flow rate measured using the modified cotton roll method. Anorexia was defined as a score of ≤29 in the Japanese version of the Council on Nutrition Appetite Questionnaire. Logistic regression analyses were used to test whether the presence of anorexia at baseline was an independent predictor of hyposalivation. Hyposalivation developed at a rate of 19.5% during the 6-year observation period. Anorexia was observed in 95 (43.2%) participants at baseline. After adjusting for potential confounding factors, anorexia (adjusted odds ratio [AOR], 2.65; 95% confidence interval [CI], 1.26-5.57) and polypharmacy (AOR, 3.29; CI, 1.06-10.19) were significant predictors of hyposalivation. Loss of appetite is independently correlated with and a risk factor for hyposalivation in older adults. Anorexia of ageing may have negative effects on the salivary flow rate in such settings. Salivation should be a standard feature in clinical assessments of the older adults.


Supplementation of vitamin C promotes early germ cell specification from human embryonic stem cells.
As the precursors of sperm and eggs, human primordial germ cells (hPGCs) emerge as early as weeks 2 to 3 of post-implantation development. Recently, robust hPGC induction models have been established in vitro with different protocols, but global 5mC/5hmC epigenetic reprogramming is not initiated in vitro. Previous studies found that vitamin C can enhance Tet (ten-eleven translocation) enzyme expression and improve 5hmC level in cells. But the effect of vitamin C supplementation on hPGC in vitro induction is still unknown. We generated a gene-edited human embryonic stem cell (hESC) line carrying a BLIMP1-mkate2 reporter by CRISPR/Cas9 technology and used flow cytometry to optimize the PGC differentiation protocol; meanwhile, the expression of PGC genes (BLIMP1, TFAP2C, SOX17, OCT4) was evaluated by qRT-PCR. When different concentrations of vitamin C were added to the induction medium, the percentage of hPGCLCs (hPGC-like cells) was analyzed by flow cytometry; dot blot and ELISA were used to detect the levels of 5hmC and 5mC. The expression of TET enzymes was also evaluated by qRT-PCR. We optimized the PGC differentiation protocol with the BLIMP1-mkate reporter hESCs, and the efficiency of PGC induction in vitro can be improved to 30~40%. When 50 μg/mL vitamin C was added, the derived hPGCLCs not only upregulated the expression of key genes involved in human early germ cell development such as NANOS3, TFAP2C, BLIMP1, and SOX17, but also increased the levels of 5hmC and TET enzymes. Taken together, supplementation of vitamin C can promote the in vitro induction of hPGCLCs from hESCs, which might be related to vitamin C-mediated epigenetic regulations during the differentiation process.


Salvage total glossectomy and total glosso-laryngectomy: Are they worth it? A GETTEC French multicenter study.
Salvage total glossectomy (TG) or total glosso-laryngectomy (TGL) remain controversial, as highly morbid procedures. The objective was to describe oncological and functional outcomes after salvage TG or TGL. We performed a multicenter retrospective study, including patients with previous neck irradiation undergoing TG or TGL for squamous cell carcinoma involving the base of tongue. We included 42 patients: 27 in the TG group and 15 in the TGL group. For the entire cohort, median OS and DFS were estimated at 19 months (95% IC [14-44]) and 10 months (95% IC [7-13]) respectively, with no difference between the two groups. After a median follow-up of 90 months, 10 patients (24%) were alive and free of disease. Att he end of follow-up, we noted a gastrostomy dependency of 89% and 87 %respectively in the TG and TGL group, and 48% of patients in the TG group had a tracheotomy. Although local control is difficult to achieve after salvage TG or TGL, these procedures are associated with acceptable survival and chance of cure for a last-resort situation. TG and TGL can be proposed in selected motivated patients after careful shared decision-making.


Thawed plasma (TP) as a substitute for intravenous immune globulin (IVIG) to prevent hypogammaglobulinemia post-therapeutic plasma exchange.
Intravenous immune globulin (IVIG) is a common treatment given after plasma exchange procedures to either prevent secondary hypogammaglobulinemia or as an adjunctive treatment for organ transplant rejection. However, side-effects are relatively common with this medication during and after infusion. This case-report describes our alternative to IVIG infusions post-plasma exchange. We hypothesize that in patients unable to tolerate IVIG, using thawed plasma as a replacement fluid provides a suitable increase in the patients post procedure immunoglobulin G (IgG) levels for patients with secondary hypogammaglobulinemia that are unable to tolerate IVIG infusions.


Effects of fructose on synthesis and degradation of purine nucleotides in isolated rat hepatocytes.
The effects of fructose on purine nucleotide synthesis and degradation were studied in isolated rat hepatocytes. Incubation of the hepatocytes with fructose resulted in deceleration of the rate of de novo purine synthesis, gauged by the rate of incorporation of precusor [14C]formate into total purines produced, and in acceleration of purine nucleotide degradation, as measured by the rate of conversion of prelabelled purine nucleotides into end-product allantoin. These effects were found to be associated with decreases in cellular content of ATP and Pi and in the metabolic availability of 5-phosphoribosyl 1-pyrophosphate. The results support the suggestion that the fructose-induced acceleration of purine degradation is mediated through activation of AMP deaminase. However, the results also suggest that decreased reutilization of hypoxanthine for IMP synthesis, due to the decreased PP-Rib-P availability, is an additional mechanism for the acceleration of purine degradation. The decreased PP-Rib-P availability is also suggested to be the main mechanism for the fructose-induced deceleration of purine synthesis.


Do United States Medical Licensing Examination (USMLE) scores predict in-training test performance for emergency medicine residents?
Residency selection committees commonly utilize USMLE scores as criteria to screen residency applicants. The purpose of this study is to evaluate the relationship between United States Medical Licensing Examination (USMLE) and American Board of Emergency Medicine (ABEM) in-training examination scores (ITEs). In an Accreditation Council for Graduate Medical Education-accredited emergency medicine residency program, data were collected for this retrospective cohort study for the classes of 2002-2006. USMLE Step 1 and 2 scores and the ABEM ITEs were recorded for each post-graduate year (PGY) within the aforementioned time frame. Step 1 and 2 scores were compared to consecutive PGY ABEM ITEs to evaluate for an association. There were 51 USMLE Step 1 and 39 Step 2 scores available for comparison with 153 ABEM ITEs. The mean USMLE Step 1 and Step 2 scores were 228.9 (range 197-252) and 228.4 (range 168-259), respectively. The mean in-training percentiles for the PGY 1, 2, and 3 years were 40.4, 68.3, and 81.7, respectively. The R-squared values for the Step 1 scores compared to the PGY 1, 2, and 3 years' ITEs were 0.25, 0.18, and 0.16, respectively. The R-squared values for Step 2 scores as compared to the ABEM ITEs for the PGY 1, 2, and 3 years were 0.43, 0.44, and 0.38, respectively. Residents who scored below 200 on either USMLE Step 1 or Step 2 had significantly lower mean ABEM ITEs than residents who scored above 200 (p < 0.05) and were 10-fold more likely than residents who scored above 220 to score below the 70th percentile in their PGY3 ABEM ITE. USMLE Step 1 scores are mildly correlated and Step 2 scores are moderately correlated with ABEM ITEs. Scoring below 200 on either test is associated with significantly lower ABEM ITEs.