Medicare hospice referral criteria for patients with amyotrophic lateral sclerosis: a need for improvement.
We conducted a retrospective review of 97 consecutive patients with amyotrophic lateral sclerosis (ALS) who were accepted into hospice care from a tertiary ALS center. Five patients met Medicare criteria at time of hospice enrollment. The mean number of hospice days was 85 (range, 1-534). All but 2 patients met hospice criteria proposed by the Columbia University ALS group. The present Medicare hospice criteria should be changed to reflect the reality of patients dying of ALS.


Peptidyl Vinyl Ketone Irreversible Inhibitors of Rhodesain: Modifications of the P2 Fragment.
In this paper, we report the design, synthesis and biological investigation of a series of peptidyl vinyl ketones obtained by modifying the P2 fragment of previously reported highly potent inhibitors of rhodesain, the main cysteine protease of Trypanosoma brucei rhodesiense. Investigation of the structure-activity relationship led us to identify new rhodesain inhibitors endowed with an improved selectivity profile (a selectivity index of up to 22 000 towards the target enzyme), and/or an improved antitrypanosomal activity in the sub-micromolar range.


Small echogenic foci in the ovaries: correlation with histologic findings.
The purpose of this study was to determine the histologic correlate of small echogenic foci in the ovary and to assess for any association with endometriosis or endosalpingiosis. Women planning to have a normal ovary surgically removed were scanned preoperatively with transvaginal sonography. If echogenic foci were present in either normal ovary on the preoperative scan, the removed ovary was scanned in a saline bath, and the surface was marked with india ink over an echogenic focus. Histologic sections were then obtained at the marked site. Echogenic foci were detected in 23 ovaries of 16 women. Possible causes were found in 17 of the 23 ovaries: hemosiderin in 6 cases, calcification in 5 cases, hemosiderin and calcification in 2 cases, clusters of inclusion cysts in 2 cases, 1 of which also had hemosiderin, and dense cortical nodules in 2 cases. Histologic findings were benign in all cases except in 1 patient who had primary peritoneal carcinoma unrelated to the echogenic foci. One ovary in another patient had both endosalpingiosis and endometriosis. One other patient had endometriosis involving a fallopian tube but not the ovary. There were no other cases of endometriosis or endosalpingiosis. Small echogenic foci in the ovaries are most frequently due to hemosiderin or calcification. A few small echogenic foci in the ovaries are associated with benign histologic changes and do not appear to be reliable indicators of endosalpingiosis or endometriosis.


Hypoxic-ischemic insult decreases glutamate uptake by hippocampal slices from neonatal rats: prevention by guanosine.
Brain injury secondary to hypoxic-ischemic disease is the predominant form of damage encountered in the perinatal period. The impact of neonatal hypoxia-ischemia (HI) in 7-day-old pups on the high-affinity [3H] glutamate uptake into hippocampal slices at different times after insult was examined. Immediately following, and 1 day after the insult there was no effect. But at 3 to 5 days after the HI insult, glutamate uptake into the hippocampus was markedly reduced; however, after 30 or 60 days the glutamate uptake into hippocampal slices returned to control levels. Also, this study demonstrated the effect of the nucleoside guanosine (Guo) on the [3H] glutamate uptake in neonatal HI injury, maintaining the [3H] glutamate uptake at control levels when injected before and after insult HI. We conclude that neonatal HI influences glutamate uptake a few days following insult, and that guanosine prevents this action.


Systematic comparison of different functionality columns for a classical pharmaceutical problem.
The performance of five reversed-phase columns which included a standard C18 phase, a polar embedded phase (amide group), a polyethyleneglycol phase, a cyano phase, and a perfluorinated phase, all coming from the same manufacturer, have been studied. They were systematically compared with a test mixture containing basic, neutral and acidic compounds of very different polarities, as well as different functional groups (acetaminophen, phenylephrine hydrochloride or phenylpropanolamine hydrochloride, chlorpheniramine maleate, 4-aminophenol, 4-chloracetanilide and 4-nitrophenol) at three pH levels (2.5, 4.6 and 7.0) and three proportions of buffer/acetonitrile (80:20, 50:50 and 20:80, v/v). The results obtained have permitted our group to develop unique applications with these columns, as these compounds are not only a test mixture, due to their chemical characteristics, but they are also usually contained in pharmaceutical formulations for the relief of common cold symptoms and have been selected as a real-life case study. Moreover, after observing the reversed-phase and normal-phase-like characteristics for certain analytes on the perfluorinated phase, a systematic study was developed in this column to understand the chromatographic behaviour of these compounds at three pH (2.5, 4.6 and 7.0) and seven different organic proportions from 20 to 80% acetonitrile. The predominant electrostatic interactions observed on the perfluorinated phase could explain its special behaviour and the high retention at higher percentages of organic solvent, especially for amine compounds, which makes this column very advantageous in working with LC/MS. Different applications with volatile buffers, such as TFA at pH 2.5 and ammonium acetate at pH 4.6 and 7.0, were also considered. Some results have been related to parameters frequently employed for column description.


Use of support vector machines and neural network in diagnosis of neuromuscular disorders.
In this study the performance of support vector machine (SVM)and back-propagation neural network were applied to analyze the classification of the electromyogram (EMG) signals obtained from normal, neuropathy and myopathy subjects. By using autoregressive (AR) modeling, AR coefficients were obtained from EMG signals. Moreover, the support vector machine and artificial neural network (ANN) were used as base classifiers. The AR coefficients were benefited as inputs for SVM and ANN. Besides, these coefficients were tested both in ANN and SVM. The results show that SVM has high anticipation level in the diagnosis of neuromuscular disorders. It is proved that its test performance is high compared with ANN.


Experimental and immunohistochemical studies concerning the major origins of the substance P-containing fibers in the lateral lemniscus and lateral parabrachial area of the rat, including the fiber pathways.
The origins and pathways of substance P-containing fibers in the lateral lemniscus and lateral parabrachial area of the rat were investigated by means of the indirect immunofluorescence technique. Following the placement of various knife cuts or lesions, the following could be concluded: (1) The cells of origin of substance P-containing fibers in the lateral lemniscus and lateral parabrachial area are localized in the ventral reticular formation of the rhombencephalon from the level of P2.8 to P7.0 in the atlas of Palkovits and Jacobowitz; (2) The fibers from these origins pass the ventral reticular formation of the rhombencephalon to form a dense bundle; (3) the fibers turn dorsally at the mid-rhombencephalon junction to reach the lateral lemniscus and lateral parabrachial area. The present study demonstrates the linking of the functions of the parabrachial area and lateral lemniscus via substance P innervation.


Matrix metalloproteinases and their inhibitors in pediatric severe acute pancreatitis.
Acute pancreatitis (AP) is increasing in incidence in adult and pediatric patients. Identification of patients at high risk for progression to severe acute pancreatitis (SAP) is crucial, as it can lead to increased mortality and health system cost. Matrix metalloproteinases (MMPs) are endopeptidases which degrade extracellular matrix proteins and increase activity of pro-inflammatory cytokines. Tissue inhibitors of metalloproteinases (TIMPs) regulate MMP activity. Prior limited studies of MMPs and TIMPs have found some to be associated with development of SAP. The aim of this study was to further investigate the role of MMPs and TIMPs in detecting pediatric patients at risk for developing moderately severe AP or SAP. Plasma samples were prospectively collected for patients <21 years of age presenting with AP between November 2015 and October 2019, along with healthy controls. Bead-based multiplex assays were utilized to test levels of 12 MMPs and TIMPs. Samples were collected from 7 subjects who developed SAP, 7 with moderately severe AP, 45 with mild AP and 44 healthy controls. MMP-9 (p = 0.04) and TIMP-1 (p = 0.01) levels were significantly higher in SAP patients. A multivariable logistic regression model using MMP-9 and TIMP-1 predicted SAP (AUROC 0.87, 95% CI 0.76-0.98). We have demonstrated that MMP9 and TIMP1 levels are increased at AP presentation in pediatric patients who developed SAP during the course of illness. Further studies are needed to validate the use of MMPs and TIMPs as predictive tools for development of SAP in pediatric pancreatitis.


On the gelation of Premna microphylla turcz extracts: The effects of supernatant and precipitate of plant ash suspension.
In order to elucidate the gelling mechanism of Premna microphylla turcz (PMT) induced by plant ash (PA), PA was fractionated into supernatant (PA-S) and precipitation (PA-P) and added to the PMT suspension, respectively. The effects of different concentrations (1-9%) and fractions (PA, PA-S, PA-P) of PA suspension on the gel properties were studied. Results showed that the electrical conductivity, content of monovalent cations, pH were higher in PA-S than PA-P. Both the PA-S and PA-P fractions induced the gelation of PMT (except for the low concentration at 1% for PA-S), and the PA-P-PMT gels showed much higher gel strength and hardness than PA-S-PMT gels. With increased concentration, the gel strength increased in PA-P-PMT, but decreased in PA-S-PMT. A hypothesis for the gelation of PMT induced by PA was proposed: the divalent cations in PA bind to carboxyl group in pectin and form gels; when higher content of PA is added, a higher pH leads to extensive dissociation of carboxyl groups thereby increases the electrostatic repulsion between pectin chains, which ultimately weakens the gelling forces. This study can provide theoretical support for further optimization of the traditional processing of PMT gels.


Behavior of metal nanoparticles in the electron beam.
Fabrication and structural observation of In, Pd and Mo nanoparticles deposited on Si(110) substrates were performed in an ultrahigh vacuum field emission transmission electron microscope. In situ and/or dynamic observation of In nanoparticles showed fluctuation of their structures. The smaller particles of size of 3-5 nm showed frequent fluctuation, while the nanoparticles of more than 10 nm in size showed relatively slower fluctuation. The bigger nanoparticles showed coalescence with a weaker beam. Pd nanoparticles of size of 3-5 nm showed structural fluctuation after 10-30 s of electron beam irradiation. Stronger beam irradiation resulted in the dissipation of the nanoparticles probably due to diffusion. Mo nanoparticles of size of 3-5 nm never showed structural fluctuation. Intensive electron beam irradiation resulted in the dissipation of the particles. The difference in structural fluctuation depending on the metal and the beam intensity, and the peculiar coalescence of In nanoparticles are discussed qualitatively.


Disappearing breast masses caused by compression during mammography.
Two cases are described in which a palpable mass and a nonpalpable mass disappeared during the performance of mammography. The disappearance is presumed to be caused by cyst rupture, resulting from the firm compression used to perform the examination. This occurrence can create confusing clinical and radiographic situations, and radiologists should be aware that occasional cyst rupture may occur.


Secretin receptors in normal and diseased human pancreas: marked reduction of receptor binding in ductal neoplasia.
Receptors for gut hormones, which are often overexpressed in cancer, are clinically relevant for receptor-targeted tumor imaging and therapy. Because the receptors for the gut hormone secretin are poorly characterized, we assessed secretin receptor expression in the main secretin target, the human pancreas. We investigated 58 non-neoplastic pancreases and 55 pancreatic tumors for receptor localization and density by in vitro receptor autoradiography using [(125)I]Tyr(10) rat secretin and for secretin receptor mRNA by reverse transcriptase-polymerase chain reaction. Secretin receptors were highly expressed in non-neoplastic ducts and lobuli and also in lower amounts in ductal neoplasias, including ductal adenocarcinoma, intraductal papillary mucinous tumors, and pancreatic intraepithelial neoplasia. Reverse transcriptase-polymerase chain reaction revealed wild-type receptor mRNA in the non-neoplastic pancreas and both wild-type and spliced variant receptor transcripts in ductal adenocarcinomas. Serous cystic tumors were highly positive for secretin receptors, whereas mucinous cystic tumors were negative. This study is the first to describe the precise secretin receptor distribution in human non-neoplastic pancreas and various pancreatic tumors. High secretin receptor expression in the non-neoplastic ducts reflects the major role of secretin in bicarbonate secretion. Reduced secretin binding in pancreatic ductal tumors may relate to (alternatively spliced) secretin receptor isoforms. Thus, secretin receptors in pancreatic tumors may represent potential clinical targets.


Supervisor-trainee continuity and the quality of work-based assessments.
Work-based assessments (WBAs) represent an increasingly important means of reporting expert judgements of trainee competence in clinical practice. However, the quality of WBAs completed by clinical supervisors is of concern. The episodic and fragmented interaction that often occurs between supervisors and trainees has been proposed as a barrier to the completion of high-quality WBAs. The primary purpose of this study was to determine the effect of supervisor-trainee continuity on the quality of assessments documented on daily encounter cards (DECs), a common form of WBA. The relationship between trainee performance and DEC quality was also examined. Daily encounter cards representing three differing degrees of supervisor-trainee continuity (low, intermediate, high) were scored by two raters using the Completed Clinical Evaluation Report Rating (CCERR), a previously published nine-item quantitative measure of DEC quality. An analysis of variance (anova) was performed to compare mean CCERR scores among the three groups. Linear regression analysis was conducted to examine the relationship between resident performance and DEC quality. Differences in mean CCERR scores were observed between the three continuity groups (p = 0.02); however, the magnitude of the absolute differences was small (partial eta-squared = 0.03) and not educationally meaningful. Linear regression analysis demonstrated a significant inverse relationship between resident performance and CCERR score (p < 0.001, r2 = 0.18). This inverse relationship was observed in both groups representing on-service residents (p = 0.001, r2 = 0.25; p = 0.04, r2 = 0.19), but not in the Off-service group (p = 0.62, r2 = 0.05). Supervisor-trainee continuity did not have an educationally meaningful influence on the quality of assessments documented on DECs. However, resident performance was found to affect assessor behaviours in the On-service group, whereas DEC quality remained poor regardless of performance in the Off-service group. The findings suggest that greater attention should be given to determining ways of improving the quality of assessments reported for off-service residents, as well as for those residents demonstrating appropriate clinical competence progression.


Improvement in the yield of oral poliovirus vaccine (Sabin strains) produced in human diploid cells.
When stationary cultures of human diploid cells in conventional Roux bottles were replaced by the development of cells in roller bottles, the yield of poliovirus, Sabin strains type 1 and 2, showed an increase of 0.5 to 1 log10. No significant difference was noticed in the yield of these viruses cultured in WI-38 and MRC-5 human diploid cells.


Abnormal DNA content in oral epithelial dysplasia is associated with increased risk of progression to carcinoma.
Oral epithelial dysplasia (OED) is a histologically detectable lesion that may progress to carcinoma but there are no accurate markers that predict progression. This study examined the development of carcinoma from oral dysplastic lesions, and the association between abnormal DNA content and progression to carcinoma. Epithelial dysplasias from the Oral Pathology Diagnostic Service were matched against the Ontario Cancer Registry database to identify cases that progressed to carcinoma. A case-control study was conducted to compare DNA image cytometry of dysplasias that progressed with those that have not progressed. For a subset of the progressed dysplasias, DNA content of the carcinoma was also analysed. A total of 8% of epithelial dysplasias progressed to carcinoma after 6-131 months. In all, 28 of 99 dysplasias showed abnormal DNA content by image cytometry. In multivariate analysis of time to progression, abnormal DNA content was a significant predictor with hazard ratio of 3.3 (95% confidence interval: 1.5-7.4) corrected for site and grade of dysplasia. Analysis of sequential samples of dysplasia and carcinoma suggested that epithelial cell populations with grossly abnormal DNA content were transient intermediates during oral cancer development. Abnormal DNA content is a significant biomarker of a subset of OED that progress to carcinoma.


Italian version of the Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS): validation and longitudinal performance.
To validate an Italian version of the Rasch-Built Overall ALS Disability Scale (ROADS) in a broad population of patients and assess its longitudinal performance over time. 270 ALS patients referring to the Motor Neuron Disease Clinic of the University of Padova and Modena (Italy) accepted to compile the Italian version of the ROADS and results were correlated with the ALSFRSr and ALSAQ-40 scores, FVC values, and creatinine or albumin blood levels. To verify test-retest reliability, patients were asked to fill in a second copy of the scale within 5-7 days. Thirty-nine patients compiled a further copy of questionnaire during the follow up visit (after 133 days on average) which allowed us a longitudinal assessment of the scale. We found a good external construct validity between ROADS and either ALSFRS-R (correlation coefficient = 0.85) or ALSAQ-40 (correlation coefficient = - 0.84). Test-retest reliability was excellent with a concordance-correlation coefficient of 0.93. Yet, we observed a significant correlation between changes over time of the ROADS normalised sum score (- 2.18 point loss per month) and those of both the ALSFRS-R (positive correlation; Rho = 0.64, p ≤ 0.0001) or the ALSAQ-40 (negative correlation; Rho = - 0.60, p = 0.014). The Italian version of ROADS proved to be a reliable marker to monitor overall disability in ALS patients. Further studies are necessary to assess its longitudinal performance.


Adrenal myelolipoma. A case report.
We report a new case in a 56 years old patient who manifested right side's pains. The abdominal CT scan showed a tumor of the right adrenal gland with fat density (size: 8 x 6 x 6 cm). This tumor was removed surgically (weight: 300 g). The histological finding revealed a proliferation of adipocyts and myeloid tissue which contains megakaryocytes, erythroid cells and lymphocyts. The outcome is good after three years of surgery. The surgical treatment becomes necessary when the tumor's size increases or it becomes symptomatic.


Cold agglutinin syndrome as a complication of Covid-19 in two cases.
Cold agglutinins are autoantibodies against RBC antigens, leading to hemolysis at less-than-physiological temperatures through complement fixation. Production can be triggered by infections, resulting in secondary cold agglutinin syndrome (CAS). This syndrome has been classically described in the setting of Mycoplasma pneumoniae infection, as well as with several viral pathogens. Here, we present two cases of cold agglutinins identified in the context of Covid-19 in critically ill patients treated at our institution. Each case was characterized by little in-vivo hemolysis, but these antibodies complicated laboratory assessment and renal replacement therapy. Management included anticoagulation and warming of dialysis circuit. Despite minimal in-vivo hemolysis, these antibodies are of clinical significance given their implications for laboratory assessment and renal replacement therapy, particularly with the frequency of multi-organ system dysfunction associated with severe Covid-19.


Effect of adding stretching to standardized procedures on cervical range of motion, pain, and disability in patients with non-specific mechanical neck pain: A randomized clinical trial.
to investigate the benefit of adding stretching exercises to cervical joint mobilization and active rotation exercises for patients with non-specific mechanical neck pain. Thirty-eight subjects with non-specific mechanical neck pain were randomly assigned to a standard procedure group (passive cervical mobilization and active cervical rotation range of motion exercise) or a combined procedure (passive cervical mobilization, active cervical rotation range of motion exercises, and stretching procedures). Mixed factorial analysis of variance was used to compare changes between groups over time in active cervical range of motion, Numeric Pain Rating Scale, Neck Disability Index, Global Rating of Change, and Pressure Pain Threshold. There was a significant change in mean active range of motion in all directions, Pressure Pain Threshold, perceived pain, disability levels, and global rating of change over time (p < 0.001). There was a significant group by time interaction in mean active range of motion during extension (p = 0.01), right rotation (p = 0.004), right and left lateral flexion (p = 0.05, and p = 0.02 respectively). However, there was no significant group by time interaction in mean active range of motion during flexion, left rotation, pain intensity (p = 0.09), right and left pressure pain threshold (p = 0.30, 0.47, respectively), and disability (p = 0.07). Both study groups improved significantly in all subjective and objective outcome measures. However, data from this study suggest that adding stretching to the standard procedures may be more effective than the standard procedure alone at improving cervical extension, right rotation, and lateral flexion active range of motion, but not pain and disability.


Influence of prophylactic anticonvulsant therapy on high-dose busulphan kinetics.
The pharmacokinetics of high-dose busulphan was studied in 17 patients during conditioning prior to bone marrow transplantation using deuterium-labeled busulphan (d8-BU). About 50% of busulphan doses 1 and 16 was replaced with d8-BU. Patients were treated with phenytoin or diazepam as prophylactic anticonvulsant therapy. Patients who received phenytoin demonstrated significantly higher clearance (mean +/- SD, 3.32 +/- 0.99 ml min-1 kg-1), a lower area under the concentration-time curve (AUC, 5,412 +/- 1,534 ng h ml-1; corrected for dose/kilogram) and a shorter elimination half-life (3.03 +/- 0.57 h) for the last dose of d8-BU (dose 16) as compared with the first dose (2.80 +/- 0.78 ml min-1 kg-1, 6,475 +/- 2,223 ng h ml-1 and 3.94 +/- 1.10 h, respectively). No difference in the above mentioned pharmacokinetic parameters was seen in patients treated with diazepam. Moreover, a continuous decrease in the steady-state level of busulphan was observed in four of seven patients in the phenytoin-treated group, whereas in the diazepam group, such a decrease was seen in only one of eight patients. We conclude that phenytoin used as prophylactic anticonvulsant therapy alters busulphan pharmacokinetics and, most probably, its pharmacodynamics. For adequate prophylactic therapy, anticonvulsants with fewer enzyme-inductive properties than phenytoin should be used.


Caution in using 3D-EAUS as the first-line diagnostic tool in the preoperative work up for perianal fistulas.
MRI is considered the de facto imaging modality for evaluating perianal fistulas, primarily due to its excellent soft tissue contrast, operator independence, multiplanar capabilities and excellent field of view. Tridimensional endoanal ultrasound (3D-EAUS) is inferior to MRI in identifying and/or evaluating ischiorectal/supralevator tracks/extensions and therefore could end up providing incomplete and even inaccurate information (e.g. misclassification of tracks) to the surgeon, with a missed track potentially leading to recurrence of the disease.


Change in the length of the ulnocarpal ligaments during radiocarpal motion: possible impact on triangular fibrocartilage complex foveal tears.
The fovea of the ulnar head is the primary attachment site for both the distal radioulnar and the ulnocarpal ligaments. Thus, both ligaments should be simultaneously affected by the traumatic avulsion of the triangular fibrocartilage complex from its ulnar attachment. Little attention, however, has been directed toward the role of the ulnocarpal ligaments in the mechanics of this type of injury. The purpose of this study was to investigate the changes in length of the ulnocarpal ligaments during various radiocarpal motions and to determine the type of radiocarpal motion that makes the ulnocarpal ligament taut and that could cause foveal avulsion if it were excessive. The 3-dimensional kinematics of the wrist joint were investigated noninvasively using a markerless bone registration technique in vivo. Magnetic resonance images of the wrists of 15 healthy volunteers were acquired in at least 5 positions during each wrist flexion-extension motion, radioulnar deviation, or the so called dart-throwing motion (radial extension-ulnar flexion motion). The 3-dimensional ligament paths of the ulnotriquetral, ulnolunate, ulnocapitate, and palmar radioulnar ligaments were modeled as the shortest paths between the fovea and the insertion point of each ligament. Changes in the 3-dimensional ligament length of each ligament between the neutral position and each wrist position were then calculated. The lengths of the ulnotriquetral and ulnocapitate ligaments increased the most on wrist radial extension, and the length of the ulnolunate ligament increased the most on wrist extension. The length of the palmar radioulnar ligament changed minimally during any motion. The ulnocarpal ligaments are likely to be stretched tensely in wrist radial extension and wrist extension. This study supports the hypothesis that one of the mechanisms responsible for a triangular fibrocartilage complex foveal tear is excessive traction of the ulnocarpal ligament caused by a fall on the outstretched hand.


Genetic studies on pancreatic proteinase in Japanese quail.
A genetic variation was found in pancreatic proteinase of Japanese quail. In eight bands of proteinase isozymes, the variation of band 5 (presence or absence) was detected among quails. Band 5 was identified as a chymotrypsin. The presence and absence of band 5 are controlled by a pair of allelic genes (Prt-5A and Prt-5a) on an autosomal locus, and gene Prt-5A, causing expression of band 5, is dominant to gene Prt-5a, a null allele for band 5. Zymograms of proteinases and their zymogens were also compared; no variation of chymotrypsinogen; corresponding to chymotrypsin Prt 5 were detected. It is suggested that the Prt-5 variant of chymotrypsin may be formed during activation of chymotrypsinogen.


The treatment of Depression comparing divided and single doses of maprotiline (Ludiomil).
A clinical trial of seventy-five patients suffering from depressive illness and treated with maprotiline (Ludiomil) is reported. Twenty-eight patients were given a single nightly dose of 75 mg and twenty-six patients were treated with 25 mg three times daily. Twenty-one patients withdrew from the trial. It was found that those patients on the nocte regime made greater improvement than those on the divided dosage. Sleep disturbances and mood swings were significantly improved on the nocte dosage. Both regimes were equally well tolerated. Special care was taken in recording any adverse drug effects in order to distinguish these from pre-existing symptoms of the illness.


Excretion of Eimeria oocysts in calves during their first three weeks after turn-out to pasture.
The numbers of Eimeria oocysts per gram (opg) and the dry matter content of 449 faecal samples taken from 54 calves in 8 herds in south west Sweden were determined during the last 2 weeks before and the first 3 weeks after the animals were turned out to pasture. While they were housed only between 0 and 580 opg were found and in 2 of the herds the numbers of oocysts remained low after turn-out. In the other 6 herds the numbers of oocysts increased after 8 to 10 days and reached a peak of between 1080 and 80,803 opg 9 to 18 days after turn-out. By 21 to 24 days after turn-out the opg-values had declined to their initial levels. Eimeria alabamensis accounted for most of the increase, but small numbers of oocysts of E. auburnensis, E. bovis, E. bukidnonensis, E. cylindrica, E. ellipsoidalis, E. pellita, E. subspherica, E. wyomingensis and E. zuernii were also observed. The interval between turn-out and the start of the increase in excretion of oocysts corresponded closely to the prepatent period of E. alabamensis and overwintered oocysts were therefore the most likely source of the infection. In 6 of the herds the dry matter content of the faeces of the calves decreased after turn-out and 56% of the calves had clinical diarrhoea. Although it cannot be excluded that change of diet may have contributed to these symptoms, E. alabamensis infection is suggested as a potential cause of diarrhoea and loss of condition in calves in Sweden during their first weeks on pasture.


Variations of Retromandibular Vein and Its Relation to Facial Nerve Within Parotid Gland.
Maxillary vein and superficial temporal vein unite to form the retromandibular vein in the parotid gland. The facial nerve lies lateral to external carotid artery and retromandibular vein. Identifying and preserving the facial nerve is the prime motto during parotidectomy. So the variations of facial nerve and the retromandibular vein should be known so as to avoid injury to both. The variations we encountered during parotid surgery will be helpful in avoiding unexpected bleeding and injury to facial nerve.


Limbic seizures increase cyclophilin mRNA levels in rat hippocampus.
Limbic seizures lead to dramatic and specific modulation of mRNA levels for many genes in the hippocampus including immediate early, growth factor and neuropeptide genes. In the present study, the influence of hilus lesion (HL)-induced seizures on the abundance of mRNA coding for cyclophilin, a peptide prolyl isomerase, in rat hippocampus was analyzed. By nuclease protection analysis a significant increase in cyclophilin mRNA levels was observed in the hippocampal dentate gyrus/CA1 subfield following HL-induced seizures. The increase began 6 h post-HL, reached a maximum (2.5-fold) at 12 h post-HL and returned to control values by 48 h post-HL. Cyclophilin mRNA levels remained stable in the cerebral cortex throughout the same seizure and post-seizure activity time span.


Improving method, properties and application of polysaccharide as emulsifier.
At present, there are still some problems for the emulsification of polysaccharides such as lack of green, efficient and industrialized methods, lack of systematic and in-depth structure-activity relationship, and need of expanding its application scope. The physical, chemical and biological methods for improving the emulsifying of polysaccharides, the emulsifying properties and influencing factors of polysaccharides and application in food were reviewed herein. It was pointed out that the future research should focus on the effect of physical-biological synergistic function on the emulsification of polysaccharides, the effect of processing process on the structure and emulsification mechanism of polysaccharides, and further expanding the application field of polysaccharides with emulsification activity to improve the quality of products.


A new genus and species of native exotic millipede in Australia (Diplopoda, Polydesmida, Paradoxosomatidae).
Taxidiotisomaportabile gen. n., sp. n. is described from scattered populations in New South Wales, Victoria and Tasmania, Australia. Populations of Taxidiotisomaportabile in Victoria, Tasmania and parts of New South Wales occur in urban, suburban and agricultural areas, with no collections of the species in natural habitats in the same district. Taxidiotisomaportabile is likely to be a native exotic species whose home range is in eastern New South Wales.


PTEN-PI3K pathway alterations in advanced prostate cancer and clinical implications.
Despite significant advances in molecular characterization and therapeutic targeting of advanced prostate cancer, it remains the second most common cause of cancer death in men in the United States. The PI3K (Phosphatidylinositol 3-kinase)/AKT (AKT serine/threonine kinase)/mTOR (mammalian target of rapamycin) signaling pathway is commonly altered in prostate cancer, most frequently through loss of the PTEN (Phosphatase and Tensin Homolog) tumor suppressor, and is critical for cancer cell proliferation, migration, and survival. This study summarizes signaling through the PTEN/PI3K pathway, alterations in pathway components commonly seen in advanced prostate cancer, and results of clinical trials of pathway inhibitors reported to date with a focus on more recently reported studies. It also reviews rationale for combination approaches currently under study, including with taxanes, immune checkpoint inhibitors and poly (ADP-ribose) polymerase inhibitors, and discusses future directions in biomarker testing and therapeutic targeting of this pathway. Clinical trials studying pharmacologic inhibitors of PI3K, AKT or mTOR kinases have demonstrated modest activity of specific agents, with several trials of pathway inhibitors currently in progress. A key challenge is the importance of PI3K/AKT/mTOR signaling in noncancerous tissues, leading to predictable but often severe toxicities at therapeutic doses. Further advances in selective pharmacologic inhibition of the PI3K/AKT/mTOR pathway in tumors, development of rational combinations, and appropriate biomarker selection to identify the appropriate tumor- and patient-specific vulnerabilities will be required to optimize clinical benefit from therapeutic targeting of this pathway.


High-performance liquid chromatographic procedure for the measurement of nitrobenzodiazepines and their 7-amino metabolites in blood.
A simple and sensitive HPLC method is described for the determination of the nitrobenzodiazepines, nitrazepam, flunitrazepam and clonazepam and their respective 7-amino metabolites in post-mortem blood. Using a single-step extraction the nitrobenzodiazepines were recovered from 0.5 ml of blood using butyl chloride. The solvent was evaporated to dryness and the reconstituted residue injected onto an HPLC system. Separation was achieved using a phenyl-bonded reversed-phase column with an acetonitrile-phosphate buffer mobile phase. Ultraviolet detection (240 nm) was used for quantitation. A linear response was observed between 0.01 and 0.60 mg/l. Assay precision between and within assays was less than 20% for all analytes. The limits of detection ranged from 0.001 to 0.008 mg/l with a limit of quantitation of 0.01 mg/l for all analytes.


Active site sharing and subterminal hairpin recognition in a new class of DNA transposases.
Many bacteria harbor simple transposable elements termed insertion sequences (IS). In Helicobacter pylori, the chimeric IS605 family elements are particularly interesting due to their proximity to genes encoding gastric epithelial invasion factors. Protein sequences of IS605 transposases do not bear the hallmarks of other well-characterized transposases. We have solved the crystal structure of full-length transposase (TnpA) of a representative member, ISHp608. Structurally, TnpA does not resemble any characterized transposase; rather, it is related to rolling circle replication (RCR) proteins. Consistent with RCR, Mg2+ and a conserved tyrosine, Tyr127, are essential for DNA nicking and the formation of a covalent intermediate between TnpA and DNA. TnpA is dimeric, contains two shared active sites, and binds two DNA stem loops representing the conserved inverted repeats near each end of ISHp608. The cocrystal structure with stem-loop DNA illustrates how this family of transposases specifically recognizes and pairs ends, necessary steps during transposition.


Evaluation of the ear ossicles with photon-counting detector CT.
Recently, computed tomography with photon-counting detector (PCD-CT) has been developed to enable high-resolution imaging at a lower radiation dose. PCD-CT employs a photon-counting detector that can measure the number of incident X-ray photons and their energy. The newly released PCD-CT (NAEOTOM Alpha, Siemens Healthineers, Forchheim, Germany) has been in clinical use at our institution since December 2022. The PCD-CT offers several advantages over current state-of-the-art energy-integrating detector CT (EID-CT). The PCD-CT does not require septa to create a detector channel, while EID-CT does. Therefore, downsizing the anode to achieve higher resolution does not affect the dose efficiency of the PCD-CT. CT is an indispensable modality for evaluating ear ossicles. The ear ossicles and joints are clearly depicted by PCD-CT. In particular, the anterior and posterior legs of the stapes, which are sometimes unclear on conventional CT scans, can be clearly visualized. We present cases of congenital anomalies of the ossicular chain, ossicular chain dislocation, tympanosclerosis, and cholesteatoma in which PCD-CT was useful. This short article reports the usefulness of PCD-CT in the 3D visualization of the ear ossicles.


Postextrasystolic repolarization abnormalities in ST-U segment in patients with ventricular arrhythmias.
Changes in U-wave amplitude after premature ventricular contractions (PVC) are known as prognostic markers in the long QT syndrome dependent on bradycardia. The purpose of the study was to find correlation between postextrasystolic ST-U segment changes and a history of sustained ventricular tachycardia or ventricular fibrillation (VT/VF). The ST-U segment configurations were taken from the 24-hour ambulatory ECG. The comparison of the morphology of these segments was performed between sinus beats preceding PVC's and first postextrasystolic beats. Two groups of patients were evaluated: 1) 32 patients with VT/VF history (VT/VF group), and 2) 36 patients with potentially malignant arrhythmia (structural heart disease with frequent PVCs and/or nonsustained VT- nsVT) (non-VT/VF group). We found T-wave changes in 8 patients (25%) from the VT/VF group and in 12 patients (33.3%) from the nonVT/VF group (P = NS) and U-wave changes in 13 patients (40.6%) and 3 patients (8.3%), respectively (P < 0.05). Other ECG indexes related to PVC's were also considered: RR interval, coupling interval (CI), prematurity index (PI), and postextrasystolic pause (PP). The analysis of these ECG indices revealed, when compared with patients without T-U-wave changes, that the occurrence of U-wave changes was significantly related to longer RR interval of the sinus rhythm preceding PVC: 1025 +/- 211 vs 918 +/- 200 ms (P < 0.05). The prematurity index was lowest in patients with U-wave changes: 0.54 +/- 0.12 vs 0.65 +/- 0.16 (P < 0.01) while postextrasystolic pauses leading to the postextrasystolic U-wave changes were significantly longer: 1383 +/- 223 vs 1130 +/- 247 ms (P < 0.001). CI did not differentiate patients: 556 +/- 108 vs 584 +/- 117 ms (P = NS). Postextrasystolic changes in ST-U segment configuration are dependent on bradycardia, low prematurity index of the PVC, and the lengthening of the postextrasystolic pause. U-wave changes more frequently appeared in patients with malignant arrhythmias. Follow-up study is needed to assess if they might be predictive for the occurrence or reoccurrence of arrhythmic episodes.


Leumorphin has an anti-apoptotic effect by activating epidermal growth factor receptor kinase in rat pheochromocytoma PC12 cells.
Endogenous opioid peptides, found in the central and peripheral nervous systems, perform neuromodulatory roles, and display a wide range of functional and pharmacological properties in vitro and in vivo. In this study, we investigated the effects of prodynorphin gene products on intracellular signaling events and cell survival in rat pheochromocytoma PC12 cells. Leumorphin, but not other prodynorphin gene products including dynorphin A, beta-neoendorphin and rimorphin (dynorphin B), increased cell viability in PC12 cells. The cytoprotective effect of leumorphin was dependent on the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways, but was insensitive to both naloxone, a general antagonist of the opioid receptor, and nor-binaltorphimine, a specific antagonist of the kappa opioid receptor. Moreover, a competition-binding assay clearly revealed that leumorphin had another binding site(s) in addition to that for the kappa opioid receptor. Interestingly, leumorphin induced activation of the epidermal growth factor receptor via a Src-dependent mechanism, which was proved to be responsible for the increased survival response. Flow cytometric and microscopic analysis showed that leumorphin rescued cells from serum deprivation-induced apoptosis. Collectively, we suggest that leumorphin prevents apoptosis via epidermal growth factor receptor-mediated activation of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways, which occur independent of the kappa opioid receptor.


Cronkhite-canada syndrome associated with gastric cancer: report of a case.
A 71-year-old man with characteristic clinical and pathological pictures of Cronkhite-Canada syndrome associated with gastric cancer is presented. Histological examinations of gastric and colonic polyps which resembled juvenile type revealed no malignant cells. The patient slowly recovered after subtotal gastrectomy and elemental diet supplement with antiplasmin agents. As for as is known to the authors, a total of 69 cases with this syndrome were reported in Japan including our patient. Of these cases 8 had cancer of the gastrointestinal tract. Two of them, including our case, had gastric cancer. Another one was associated with gastric cancer but not intestinal polyposis. The remaining 5 cases were associated with colonic cancer. Caution must be paid to the fact that cachexia or malabsorption in some patients with this syndrome results from gastrointestinal malignancy. The prognosis of this syndrome consisted of 20 deaths including 2 postoperative deaths, 33 of improvement including 4 of natural remission and 4 of remission after gastrectomy or colectomy, 7 unchanged and the remainder not described.


Enzyme electrodes based on sono-gel containing ferrocenyl compounds.
An amperometric-mediated glucose sensor has been developed by employing a silica sono-gel carbon composite electrode (SCC). The chosen mediators, ferrocene (Fc) and 1,2-diferrocenylethane (1), have been immobilized in the sono-gel composite matrix. The complex 1 has been employed for the first time as an electron transfer mediator for signal transduction from the active centre of the enzyme to the electrode conductive surface. After the optimisation of the construction procedure the best operative conditions for the analytical performance of the biosensor have been investigated in terms of pH, temperature and applied potential. Cyclic voltammetric and amperometric measurements have been used to study the response of both the glucose sensors, which exhibit a fast response and good reproducibility. The sensitivity to glucose is quite similar (6.7+/-0.1 microA/mM versus 5.3+/-0.1 microA/mM) when either Fc or 1 are used as mediators as are the detection limit ca. 1.0 mM (S/N=3) and the range of linear response (up to 13.0 mM). However, the dynamic range for glucose determination results wider when using 1 (up to 25.0 mM). The apparent Michaelis-Menten constants, calculated from the reciprocal plot under steady state conditions, are 27.7 and 31.6 mM for SCC-Fc/GOx and SCC-1/GOx electrodes, respectively, in agreement with a slightly higher electrocatalytic efficiency for the mediator 1.


Intracellular Infection of Diverse Diatoms by an Evolutionary Distinct Relative of the Fungi.
The Fungi are a diverse kingdom, dominating terrestrial environments and driving important ecologies. Although fungi, and the related Opisthosporidia, interact with photosynthetic organisms on land and in freshwater as parasites, symbionts, and/or saprotrophic degraders [1, 2], such interactions in the marine environment are poorly understood [3-8]. One newly identified uncultured marine lineage has been named novel chytrid-like-clade-1 (NCLC1) [4] or basal-clone-group-I [5, 6]. We use ribosomal RNA (rRNA) encoding gene phylogenies to demonstrate that NCLC1 is a distinct branch within the Opisthosporidia (Holomycota) [7]. Opisthosporidia are a diverse and largely uncultured group that form a sister branch to the Fungi or, alternatively, the deepest branch within the Fungi, depending on how the boundary to this kingdom is inferred [9]. Using culture-free lineage-specific rRNA-targeted fluorescent in situ hybridization (FISH) microscopy, we demonstrate that NCLC1 cells form intracellular infection of key diatom species, establishing that intracellular colonization of a eukaryotic host is a consistent lifestyle across the Opisthosporidia [8-11]. NCLC1 infection-associated loss and/or envelopment of the diatom nuclei infers a necrotrophic-pathogenic interaction. Diatoms are one of the most diverse and ecologically important phytoplankton groups, acting as dominant primary producers and driving carbon fixation and storage in many aquatic environments [12-14]. Our results provide insight into the diversity of microbial eukaryotes that interact with diatoms. We suggest that such interactions can play a key role in diatom associated ecosystem functions, such as the marine carbon pump through necrotrophic-parasitism, facilitating the export of diatoms to the sediment [15, 16].


Effects of partial ileocolectomy and Crohn's disease on biliary lipid secretion.
The effects of interruption of the enterohepatic circulation of bile acids on biliary lipid secretion have only been studied experimentally, and quantitative data in patients are lacking. Therefore, biliary lipid secretion during steady-state meal perfusion of the duodenum was studied in six patients with partial ileocolectomy, five patients with Crohn's disease, and five normal subjects. Bile acid outputs in the resection patients were significantly lower than in normal controls, (6.87 +/- 2.10 mmol/6 hr and 13.5 +/- 2.16, respectively; P less than 0.001) and were also decreased in two of the five Crohn's disease patients. Bile acid outputs in patients with resection progressively decreased in the course of the perfusion study; phospholipid and cholesterol secretion did not decrease to the same extent, and cholesterol saturation gradually increased. Bile of these patients, therefore, was frequently supersaturated due to uncoupling of bile acid secretion and outputs of the other biliary lipids. Bile acid outputs, although decreased, did not reach very low values, which shows that the enterohepatic circulation was not totally interrupted. Chenodeoxycholic acid was the main bile acid component of bile in patients with ileocolonic resection. Deoxycholic acid was absent from bile of four resected patients and two Crohn's patients. Two patients with active Crohn's disease had low bile acid outputs despite only moderate fecal bile acid losses. Therefore, decreased outputs may be caused by decreased bile acid pool not compensated for by increased bile acid synthesis in severely ill patients.


The role of N-glycan modification of TNFR1 in inflammatory microglia activation.
Accumulating evidences demonstrated that microglia activation and the autocrine loop of tumor necrosis factor-α (TNFα) greatly contribute to the pathogenesis of several CNS diseases. TNFα exerts its biological effects by interacting with two different receptors: TNF receptor 1 (TNFR1) and TNFR2. The classic proinflammatory activity of TNFα is mainly mediated by TNFR1. In the present study, we found that TNFR1 was modificated by N-glycosylation on Asn151 and Asn202 in microglia. The N-glycosylation of TNFR1 could facilitate its capability of binding to TNFα and further promote the formation of TNFα autocrine loop in microglia stimulated by TNFα, resulting in excessive microglia activation and CNS inflammation. All these processes were related to TNFR1-mediated NF-κB pathways. Elimination of N-glycosylation did not affect the subcellular transportation and cell surface localization of TNFR1, but suppressed ligand-binding affinity. These findings indicated that the N-glycosylation of TNFR1 played an important role during microglia activation in CNS inflammation. By this study, we aimed to provide some valuable experimental evidence for a better understanding of the significance of protein glycosylation in microglia inflammatory activation and CNS disease.


[Investigation of the prevalence of drug-induced gingival overgrowth in renal transplant recipients medicated with cyclosporine A or tacrolimus].
To investigate the prevalence of gingival overgrowth(GO) in a group of renal transplant recipients medicated with cyclosporine A(CsA) in comparison to those medicated with tacrolimus(Tcr). 107 renal transplant recipients ( 85 CsA and 25 Tcr) were recruited into this study. Demographic, pharmacologic and periodontal data was recorded. The prevalence and severity of GO were compared between the two groups. The data was analyzed by SPSS13.0 software package for independent sample t test, chi(2) test, Mann-Whitney U test and stepwise regression analysis. The prevalence of GO in the CsA group(49%)was significantly higher than that in the Tcr group(16%)(P<0.05). The CsA group showed a higher mean GO score (30.3+/-15.5) compared with the Tcr group(17.5+/-9.6) (P<0.001).In addition, the patients with GO presented a significantly higher plaque index and papilla bleeding index than those without GO in two groups(P<0.05). The prevalence of GO is higher in renal transplant recipients taking CsA compared to Tcr. Plaque-induced gingival inflammation has a close relation with the severity of GO.


Becker's nevus.
Becker's nevus is a benign lesion that may be congenital or acquired, macular or papular, hairless or hypertrichotic. It is most commonly located on the upper trunk of young men. Histologic examination shows characteristic changes, but dermal nevus cells are never present. Bony and soft tissue structural anomalies occur with increased frequency in patients with Becker's nevus.


Selective luminescence determination of cysteine by using terbium-modified silver nanoparticles or terbium-modified graphene quantum dots.
Two methods for the luminescence determination of cysteine (Cys) are presented. They make use of either silver nanoparticles (Ag NPs) or graphene quantum dots (GQDs), both doped with terbium(III). The methods are based on the finding that Cys quenches the green luminescence of Tb(III)-Ag NPs and Tb(III)-GQDs. The excitation/emission maxima are at 306/545 and 257/545 nm, for both nanoprobes, respectively. Response is linear in the 0.28-5.0 μg mL-1 Cys concentration range for the Tb(III)-Ag NP system, and from 0.05-3.0 μg mL-1 for the Tb(III)-GQD system. The respective limits of detection are 0.09 and 0.015 μg mL-1. The probes were applied to the time-resolved luminometric determination of Cys in (spiked) food supplements and gave satisfactory results. Graphical abstractSchematic representation of the quenching by cysteine (Cys) of the time-resolved luminescence (TSL) of terbium-graphene quantum dots [Tb(III)-GQD] and of terbium-silver nanoparticles [Tb(III)-Ag NP].


The effect of pre-operative diagnosis on patient reported outcomes in patients undergoing colorectal operations: A prospective study.
Patient Reported Outcomes (PROs) capture peri-operative fatigue, pain, and quality of life and influence outcomes in gastrointestinal surgery. We compared peri-operative PROs in patients undergoing colorectal operations for neoplastic versus non-neoplastic processes. Patients undergoing colectomy were enrolled prospectively. Demographics and PROs were gathered preoperatively and on post-operative day (POD) 2, 7, 14, and 30 using the validated Linear Analog Self-Assessment (LASA). Severe pain was defined as pain ≥5, severe fatigue as ≥7, a quality of life deficit as QOL ≤5. We included 192 patients, median age 54 years, 44% female, 88 (46%) for neoplasia. Morbidity was 38%, mortality 3%. Pre-operatively, non-neoplasia patients reported significantly more pain, fatigue, and QOL deficits than neoplasia patients. Severe pain at POD 2 was a positive predictor for complications (p-value< 0.05). In patients undergoing colorectal surgery, diagnosis influences peri-operative PROs; early severe pain and fatigue may predict complications.


The effect of hypoxia on the proteomic signature of pig adipose-derived stromal/stem cells (pASCs).
Human adipose-derived stem cells (ASCs) have potential to improve wound healing; however, their equivalents from domestic animals have received less attention as an alternative cell-based therapy for animals or even humans. Hypoxia is essential for maintaining stem cell functionality in tissue-specific niches. However, a cellular response to low oxygen levels has not been demonstrated in pig ASCs. Hence, the goal of our study was to characterize ASCs isolated from the subcutaneous fat of domestic pigs (pASCs) and examine the effect of hypoxia on their proteome and functional characteristics that might reproduce pASCs wound healing ability. Analysis of immunophenotypic and functional markers demonstrated that pASCs exhibited characteristics of mesenchymal stem cells. Proteomic analysis revealed 70 differentially abundant proteins between pASCs cultured under hypoxia (1% O2) or normoxia (21% O2). Among them, 42 proteins were enriched in the cells exposed to low oxygen, whereas 28 proteins showed decrease expression following hypoxia. Differentially expressed proteins were predominantly involved in cell metabolism, regulation of focal and intracellular communication, and attributed to wound healing. Functional examination of hypoxic pASCs demonstrated acquisition of contractile abilities in vitro. Overall, our results demonstrate that hypoxia pre-conditioning impacts the pASC proteome signature and contractile function in vitro and hence, they might be considered for further cell-based therapy study on wound healing.


5'-N-ethylcarboxamido[8-3H]adenosine binds to two different adenosine receptors in membranes from the cerebral cortex of the rat.
In the present study it is reported that [3H]NECA binds in a specific and saturable manner to membranes from the cerebral cortex of the rat. Scatchard analysis revealed two binding sites. The high affinity binding site (Kd 10.66 +/- 5 nM, Bmax 0.305 +/- 0.05 pmol/mg prot) was characterized by the following features: maximum binding at 25 degrees C, sensitivity to pretreatment with NEM and regulation by Gpp[NH]p, enhancing of binding in the presence of 1.0 mM MgCl2 and 1.5 mM CaCl2; the rank order of potency of several analogues of adenosine in competing with [3H]NECA for binding, was CHA greater than L-PIA greater than NECA greater than CADO. The low affinity binding site (Kd261.8 +/- 50 nM, Bmax 4.19 +/- 0.33 pmol/mg prot) showed maximum binding at 0 degrees C, insensitivity to pretreatment with NEM up to 1 mM and to regulation by Gpp[NH]p, and inhibition of binding in the presence of MgCl2 and CaCl2. The low affinity site was also present in membranes not pretreated with adenosine deaminase and, even in this condition, an IC50 of 188.5 +/- 36 nM for NECA and an IC50 of 4.35 +/- 0.20 microM for adenosine were found. It is concluded that the high affinity binding site is similar to the A1 adenosine receptors. The low affinity binding site is not classifiable among the A-type adenosine receptors, although it shows peculiar features shared both with the human platelet A2 receptor and the adenosine receptor formerly studied with [3H]adenosine in membranes from the brain of the rat; these results could reflect heterogeneity of adenosine receptors in central nervous system.


Mersilene ribbon closure of the median sternotomy: an improvement over wire closure.
With the increased utilization of median sternotomy in thoracic surgery, some difficulties have arisen with closure of the sternum. This article presents a simple, easy-to-perform method of sternal closure utilizing reinforcement of the sternal halves with a material that is less likely to cut through the sternum and that is readily available.


Cardiac sympathetic stimulation increases cardiac contractility but decreases contractile efficiency in canine hearts in vivo.
The effect of cardiac sympathetic stimulation on cardiac contractile efficiency was studied in dogs. In 19 anesthetized and open-chest dogs, left ventricular (LV) pressure, LV volume, coronary blood flow and coronary venous oxygen saturation were measured simultaneously. The LV end-systolic pressure volume relations (ESPVR) and the relation between myocardial oxygen consumption (VO2)-pressure volume area (PVA) were obtained during a transient occlusion of the inferior vena cava before and after sympathetic stimulation (9V, 6 Hz, 40 sec) both with and without 50 mg/kg of 2,3-butanedione monoxime (BDM). Without BDM, sympathetic stimulation increased the slope of ESPVR by 62% (p<0.05), the slope of the VO2-PVA line by 19% (p<0.05) and the y-axis intercept of the VO2-PVA by 65% (p<0.05). With BDM, the increase in the slope of the VO2-PVA line became insignificant although other responses were similarly preserved. These data imply that cardiac sympathetic stimulation decreases cardiac contractile efficiency through mechanisms by which norepinephrine-induced beta-adrenergic activation enhances myosin ATPase-operating ATP hydrolysis in crossbridge formation.


Feasibility and efficacy of minimally invasive stand-alone surgical ablation of atrial fibrillation. A single-center experience.
Minimally invasive surgical ablation for atrial fibrillation (AF) has shown good results and low complications incidence. Our objective was to evaluate feasibility and efficacy of this technique in our center. The procedure included pulmonary vein isolation, ganglionic plexi ablation, ligament of Marshall resection, and left atrial appendage exclusion through beating heart minimally invasive bilateral thoracotomies. Patients were monitored daily by telemedicine during the first 4 months and then by quarterly 24-h Holter monitoring or by implantable cardiac monitor. Ablation success was defined as freedom from any atrial tachyarrhythmia recurrence lasting more than 30 s and from antiarrhythmic drugs. All patients were followed up for a minimum of 12 months. Twenty-two consecutive patients with AF, paroxysmal in 27% and persistent in 73%, were treated. Mean age was 63 ± 10 years, 86% were men. Seventy-three percent of patients had previously undergone to one or more catheter ablations. Median follow-up period was 22 months (25°-75° percentile, 20-27). Patients free from any arrhythmia recurrence for at least 6 consecutive months discontinued antiarrhythmic therapy. Ablation was successful in 73% of patients at 12 months. Freedom from AF recurrences independently from antiarrhythmic therapy status was 91% at 12 months. Results were consistent in patients that reached 24 months follow-up. There were no deaths. Complications were: one conversion to sternotomy owing to thoracic adherences, one pacemaker implant, and one postoperative hemothorax requiring surgical revision. Our results show that minimally invasive surgical ablation was feasible and gave satisfactory results at long-term term follow-up in patients with AF.


Expression, purification and virucidal activity of two recombinant isoforms of phospholipase A2 from Crotalus durissus terrificus venom.
The global emergence and re-emergence of arthropod-borne viruses (arboviruses) over the past four decades have become a public health crisis of international concern, especially in tropical and subtropical countries. A limited number of vaccines against arboviruses are available for use in humans; therefore, there is an urgent need to develop antiviral compounds. Snake venoms are rich sources of bioactive compounds with potential for antiviral prospection. The major component of Crotalus durissus terrificus venom is a heterodimeric complex called crotoxin, which is constituted by an inactive peptide (crotapotin) and a phospholipase A2 (PLA2-CB). We showed previously the antiviral effect of PLA2-CB against dengue virus, yellow fever virus and other enveloped viruses. The aims of this study were to express two PLA2-CB isoforms in a prokaryotic system and to evaluate their virucidal effects. The sequences encoding the PLA2-CB isoforms were optimized and cloned into a plasmid vector (pG21a) for recombinant protein expression. The recombinant proteins were expressed in the E. coli BL21(DE3) strain as insoluble inclusion bodies; therefore, the purification was performed under denaturing conditions, using urea for protein solubilization. The solubilized proteins were applied to a nickel affinity chromatography matrix for binding. The immobilized recombinant proteins were subjected to an innovative protein refolding step, which consisted of the application of a decreasing linear gradient of urea and dithiothreitol (DTT) concentrations in combination with the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate hydrate (CHAPS) as a protein stabilizer. The refolded recombinant proteins showed phospholipase activity and virucidal effects against chikungunya virus, dengue virus, yellow fever virus and Zika virus.


A new species of Nemoura (Plecoptera: Nemouridae) from South of the Russian Far East.
A new species of Plecoptera from the Nemoura ovocercia group, Nemoura khasanensis sp. n. from the Primorsky Region, south of the Russian Far East, is described and illustrated. The diagnostic characters for separation from other members of the oviocercia group are provided.


[Comparative study of manual and mechanical insertion of self-threading parapulpal pins].
Analysis of the traction resistance of 18 TMS Link-Plus self-threading pulp pins (Whaledent Int.) some inserted manually, others using a low-speed device in a group of extracted teeth revealed no statistically significant differences between the two groups. It therefore seems that the tiny fractures observed under microscopic examination are caused by the threading mechanism per se and not by the way it is carried out.


CRAFFT: An Activity Prediction Model based on Bayesian Networks.
Recent advances in the areas of pervasive computing, data mining, and machine learning offer unique opportunities to provide health monitoring and assistance for individuals facing difficulties to live independently in their homes. Several components have to work together to provide health monitoring for smart home residents including, but not limited to, activity recognition, activity discovery, activity prediction, and prompting system. Compared to the significant research done to discover and recognize activities, less attention has been given to predict the future activities that the resident is likely to perform. Activity prediction components can play a major role in design of a smart home. For instance, by taking advantage of an activity prediction module, a smart home can learn context-aware rules to prompt individuals to initiate important activities. In this paper, we propose an activity prediction model using Bayesian networks together with a novel two-step inference process to predict both the next activity features and the next activity label. We also propose an approach to predict the start time of the next activity which is based on modeling the relative start time of the predicted activity using the continuous normal distribution and outlier detection. To validate our proposed models, we used real data collected from physical smart environments.


Bleomycin-induced chromosome breakage in G2 lymphocytes of retinoblastoma patients.
Retinoblastoma (Rb) cells may be more sensitive to X-irradiation than normal cells when assayed for clonogenic survival, suggesting that such sensitivity can be used as a trait for detecting RB1 gene carriers. We studied induction of chromosome damage in lymphocytes from patients with Rb by the radiomimetic antineoplastic antibiotic, bleomycin (BL). Lymphocytes were treated in G2 for 4 h at four concentrations of the drug (0.0, 0.3, 0.9, and 2.7 micrograms/ml), and chromosome damage was evaluated. No difference in levels of spontaneous or induced damage was detected among hereditary Rb, non-hereditary Rb, and normal lymphocytes. The role of X-ray treatment in the induction of second tumors in Rb patients is discussed.


Successful identification of rare variants using oligogenic segregation analysis as a prioritizing tool for whole-exome sequencing studies.
We aim to identify rare variants that have large effects on trait variance using a cost-efficient strategy. We use an oligogenic segregation analysis as a prioritizing tool for whole-exome sequencing studies to identify families more likely to harbor rare variants, by estimating the mean number of quantitative trait loci (QTLs) in each family. We hypothesize that families with additional QTLs, relative to the other families, are more likely to segregate functional rare variants. We test the association of rare variants with the traits only in regions where at least modest evidence of linkage with the trait is observed, thereby reducing the number of tests performed. We found that family 7 harbored an estimated two, one, and zero additional QTLs for traits Q1, Q2, and Q4, respectively. Two rare variants (C4S4935 and C6S2981) segregating in family 7 were associated with Q1 and explained a substantial proportion of the observed linkage signal. These rare variants have 31 and 22 carriers, respectively, in the 128-member family and entered through a single but different founder. For Q2, we found one rare variant unique to family 7 that showed small effect and weak evidence of association; this was a false positive. These results are a proof of principle that prioritizing the sequencing of carefully selected extended families is a simple and cost-efficient design strategy for sequencing studies aiming at identifying functional rare variants.


Broca's faculté du langage articulé: Language or Praxis?
De Oliveira-Souza, Moll, and Tovar-Moll (this issue) historically reevaluate that Paul Broca's aphemia should be considered as a kind of apraxia rather than aphasia. I argue that such a claim is unwarranted, given the interpretation of the faculty of speech Broca derived from his predecessors, Jean-Baptiste Bouillaud and Franz Joseph Gall, and also with a view on the then generally held opinion that the terms aphémie and aphasie were synonyms. I will discuss evidence that patients such as Leborgne, producing only very few words or syllables, suffer from a global aphasia, affecting all modalities, despite Broca's statement that Leborgne's comprehension was intact. I also point to Broca's claim that the faculty of speech, located in the left anterior hemisphere, is independent from hand preference because it is an intellectual and not a motor function, and to his statement that the cerebral convolutions are not motor organs. I finally contend that, in order to determine whether a given language problem should be labeled as aphasia or apraxia, it is crucial to first be clear on the components of old and new models of language production.


Personality traits influence contest outcome, and vice versa, in a territorial butterfly.
Holding a territory is often crucial in order to acquire key resources, including mating partners. However, few studies have investigated the role of animal personality in the context of territorial conflicts and how the contest outcome itself may influence personality traits. We studied personality in male Speckled wood butterflies, Pararge aegeria, before and after territorial contests for sunspot territories. Before interactions, boldness decreased with age, while activity and exploration were only influenced by ambient conditions. Neither age nor morphology did influence the probability to win contests, but winners were more active and more explorative than losers and, moreover, males that received a red wing mark were more likely to be winners. Butterflies that lost a contest showed pronounced behavioural changes. Mean boldness increased and its repeatability was disrupted, while no such change was detected in winners. The observed boldness increase in losers may be explained by a 'desperado effect', though its implication for successive contests remains unknown. Given that territoriality is expected to have important consequences for reproductive success, our results suggest that personality traits may indirectly contribute to individual fitness by influencing the ability to gain access to mate-location patches.


Anti-inflammatory Properties of Bioactive Peptide Derived from Gastropod Influenced by Enzymatic Hydrolysis.
The visceral mass of the gastropod, Harpa ventricosa was hydrolysed using trypsin, alcalase and pepsin for 12 h to produce protein hydrolysates. Subsequently, the active hydrolysate was observed in the 3rd hour of tryptic hydrolysate (29.17 ± 0.62 and 34.85 ± 0.55 %) using human red blood cell (HRBC) membrane stabilization and albumin denaturation (AD) assays. The active hydrolysate was fractionated by membrane filtration unit, where <10-kDa fraction revealed better anti-inflammatory activity with IC50 value 6.27 ± 0.05 and 5.38 ± 0.02 mg/ml for HRBC and AD assays, respectively. Additionally, the active fraction contains essential and non-essential (aspartic acid, arginine, glutamic acid and leucine) amino acids and, sequentially, the active fraction was further purified using consecutive chromatography, in which fraction C-II exhibited strong anti-inflammatory activity (HRBC 56.02 ± 0.52 and AD 50.71 ± 1.10 % assays). The non-toxic, low molecular weight (690.2 Da) hexapeptide (Ala-Lys-Gly-Thr-Trp-Lys) suppressed the nitric oxide (NO) and pro-cytokine production in a dose-dependent manner on THP-1 cell lines.


Development of targeted gene delivery system based on liposome and PAMAM dendrimer functionalized with hyaluronic acid and TAT peptide: In vitro and in vivo studies.
The development of gene delivery systems is essential to improve their transfection efficiency and cytotoxicity. Combination of lipid and polymeric nanoparticles with the characteristics of both systems have been considered as a next-generation gene delivery platform. In the current study, we designed a novel and efficient targeted gene delivery system based on liposome and PAMAM dendrimer in cancer cells. Two polymeric formulations containing polyamidoamine-TAT (PAMAM-TAT) and PAMAM-TAT-Hyaluronic acid (HA) and two lipopolymeric carriers including PAMAM-TAT-Liposome and PAMAM-TAT-HA-Liposome were complexed with the enhanced green fluorescent protein (EGFP) plasmid and then evaluated in terms of physicochemical characteristics. The cytotoxicity and transfection efficiency of these synthetized carriers were accomplished against murine colon carcinoma cell line (C26). The biodistribution of polyplexes and lipoployplexes was also evaluated in the C26 tumor bearing mice. The results showed no significant toxicity for all designed nanoparticles (NPs) in C/P4. The highest gene expression was observed using lipopolyplex PAMAM-TAT-HA-Liposome in C/P4 (ratio polymer/DNA; wt/wt). Biodistribution study demonstrated more aggregation of targeted lipopolyplex in tumor cells than other nanoparticles (NPs). It could be concluded that the developed targeted lipopolymeric complex could serve as promising nanotherapeutic system for gene therapy.


Molecular characterization of familial hypercholesterolemia in Spain.
Familial hypercholesterolemia (FH), characterized by isolated elevation of plasmatic low-density lipoprotein (LDL) cholesterol and premature coronary heart disease (CHD), is associated with mutations in three major genes: LDL receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin 9 (PCSK9). We have analyzed 5430 Spanish index cases and 2223 relatives since 2004 with LIPOchip(®) genetic diagnostic platform, a microarray for the detection of Spanish common mutations in these three genes, including copy number variation (CNV) in LDLR, followed by sequencing analysis of the coding regions of LDLR and exon 26 of APOB, when the result is negative. Samples were received from hospitals of all around Spain. The preferred clinical criterion to diagnose FH was Dutch Lipid Clinic Network (DLCN) score. Our results show that there is a broad spectrum of mutations in the LDLR gene in Spain since about 400 different mutations were detected, distributed along almost the whole LDLR gene. Mutations in APOB (mainly p.Arg3527Gln) covered 6.5% of positive cases and only one PCSK9 mutation was detected. We found correlation between more severe mutations and the clinical diagnosis but also that 28% of FH patients harboring mutations do not have a definite clinical diagnosis. This study analyzes the mutation spectrum in Spain, remarks the importance of genetic diagnosis of FH patients, as well as the cascade screening, and shows how it is being carried out in Spain.


A novel combined score of biomarkers in sputum may be an indicator for lung cancer: A pilot study.
Lung cancer is a leading cause of morbidity and mortality worldwide and there is an urgent need for sensitive, specific, and reliable biomarkers. The study population included 60 patients (31 with lung cancer and 29 with chronic obstructive pulmonary disease [COPD]) and thirty healthy individuals comprised the control group. Measurements of neutrophil, beclin-1, VEGF, ICAM, VCAM, and TNF-alpha levels in induced sputum were analyzed as possible biomarkers for lung cancer. Neutrophil, beclin-1, VEGF, ICAM and TNF-alpha levels of lung cancer patients differed significantly compared to those of COPD patients and healthy controls. A novel combined-score was created which was found to increase the likelihood to belong to the cancer group by 70% (odds-ratio 1.70 CI = 1.310-2.224,p < 0.001). Biomarkers of autophagy, angiogenesis and inflammation in lung-cancer patients are significantly different from controls, and combination of these markers may be an indicator for lung cancer.


Imaging techniques in Veterinary Medicine. Part I: Radiography and Ultrasonography.
In Veterinary Medicine all the Imaging techniques are used and described but, due to organizational, managerial and, mostly, economical reasons, Radiography and Ultrasonography are the most used. Veterinary Radiology teaching has a relatively small number of educational credits in the degree courses but, nowday, educational opportunities are remarkably increased thanks to a number of post-degree courses and masters, organized both by the universities and private veterinary associations. The relevance of Diagnostic Imaging is particularly true in Veterinary Medicine, in which Radiology could be considered "indispensable" for diagnosis, prognosis and follow up. Furthermore, it should not be forgotten that the diagnostic image represents a "document" and, has a relevant role in legal medical debats. In this first part, Radiography and Ultrasonography are described.


Frequency of cardiac contusion in nonpenetrating chest injury.
Seventy-five patients with nonpenetrating chest injuries were evaluated with electrocardiography, cardiac enzyme determination, 2-dimensional echocardiography and radionuclide ventriculography to document the incidence of cardiac abnormalities. Although the electrocardiograms showed ST-T wave changes in 25 patients (33%), sensitivity (47%) and specificity (79%) for echocardiographic and radionuclide abnormalities were poor. Cardiac enzymes were abnormal in 10 patients (13%), sensitivity for echocardiographic or radionuclide abnormalities, or both, was 29% and specificity 90%. Wall motion abnormalities were detected in 11 patients (18%) by radionuclide studies and in 3 patients (6%) by echocardiography. A pericardial effusion was present in 5 patients (10%). Two patients (4%) died of noncardiac causes; neither had wall motion abnormalities. This study documents the favorable outcome of patients with blunt chest injuries and does not suggest that echocardiography or radionuclide studies should be performed routinely on such patients.


Natural products targeting mitochondria: emerging therapeutics for age-associated neurological disorders.
Mitochondria are the primary source of energy production in the brain thereby supporting most of its activity. However, mitochondria become inefficient and dysfunctional with age and to a greater extent in neurological disorders. Thus, mitochondria represent an emerging drug target for many age-associated neurological disorders. This review summarizes recent advances (covering from 2010 to May 2020) in the use of natural products from plant, animal, and microbial sources as potential neuroprotective agents to restore mitochondrial function. Natural products from diverse classes of chemical structures are discussed and organized according to their mechanism of action on mitochondria in terms of modulation of biogenesis, dynamics, bioenergetics, calcium homeostasis, and membrane potential, as well as inhibition of the oxytosis/ferroptosis pathway. This analysis emphasizes the significant value of natural products for mitochondrial pharmacology as well as the opportunities and challenges for the discovery and development of future neurotherapeutics.


A 1H-NMR study of the permeation of glycolic acid through phospholipid membranes.
The transmembrane permeability coefficient of the alpha-hydroxyacid, glycolic acid, has been measured for egg phosphatidylcholine large unilamellar vesicles. The determination of the vesicle concentration independent first-order rate constant for membrane transport and the permeability coefficient were made using an NMR technique employing shift agents. Both the temperature dependence and the dependence on cholesterol content were investigated. The activation energy and the Arrhenius pre-exponential factor were found to be dependent on the cholesterol content. A marked increase in both parameters was observed up to 20 mol% cholesterol, with a further, small increase up to 50%. The pH dependence of permeability was also investigated. An increase in permeability is observed with a decrease in pH, providing a possible explanation for the effectiveness of glycolic acid in skin treatment.


The exercise IL-6 enigma in cancer.
Interleukin (IL)-6 elicits both anticancer and procancer effects depending on the context, which we have termed the 'exercise IL-6 enigma'. IL-6 is released from skeletal muscles during exercise to regulate short-term energy availability. Exercise-induced IL-6 provokes biological effects that may protect against cancer by improving insulin sensitivity, stimulating the production of anti-inflammatory cytokines, mobilising immune cells, and reducing DNA damage in early malignant cells. By contrast, IL-6 continuously produced by leukocytes in inflammatory sites drives tumorigenesis by promoting chronic inflammation and activating tumour-promoting signalling pathways. How can a molecule have such opposing effects on cancer? Here, we review the roles of IL-6 in chronic inflammation, tumorigenesis, and exercise-associated cancer prevention and define the factors that underpin the exercise IL-6 enigma.


Distribution of TAP gene polymorphisms and extended MHC haplotypes in Mexican Mestizos and in Seri Indians from northwest Mexico.
The study of the genetic structure is very useful for investigating the biological significance of polymorphism and may provide clues to understand population origins. We present TAP1/TAP2 gene analysis in the Seri indians from Sonora, and in Mestizos from the highlands of Mexico. Thirty-two Seri and 89 Mestizos were studied. TAP genes were typed using the ARMS-PCR technique. The most frequent alleles in Seri were: TAP1*0101/02, (68.8%); TAP1*02011/02012, (31.2%); TAP2*0201, (38.7%) and TAP2*0101, (29.0%). TAP1*0301, TAP1*0401, TAP2*0102 TAP2*0103 and TAP2H were absent in them. For Mestizos, the prevalent alleles were: TAP1*0101/02 (75.8%); TAP1*02011/12 (20.3%); TAP2*0101 (45.4%) and TAP2*0201 (29.3%). These results are similar to those found in Kaingang and Caucasians from Brazil, four Mediterranean, other Caucasians, two Oriental and one African group. In Seri, the extended prevalent haplotypes are typically Amerindian, such as TAP1*0101/2-TAP2*0201-QBP3.21-DQB1*0302-QAP*3.1-DQA1*03011-DRB1*0407-B*3501-A*0201 (HF = 16.6%). Thirty-two extended haplotypes were found in Seri, although TAP contributed scarcely to diversity. Mestizos show Amerindian and Caucasian combinations. No difference was detected in the distribution of amino acids in the individual variable sites, between both groups. These findings are the basis for further anthropological studies and to explore the contribution of TAP genes to disease expression in Mexicans.


Effect of a wound cleansing solution on wound bed preparation and inflammation in chronic wounds: a single-blind RCT.
Research into surfactant solutions for the debridement of chronic wounds suggests that surfactants may support wound bed preparation (WBP) in chronic wounds, however their efficacy has not been evaluated in randomised controlled trials (RCTs). Our aim was to assess the clinical efficacy of a propylbetaine-polihexanide (PP) solution versus normal saline (NS) solution in WBP, assessing inflammatory signs and wound size reduction in patients with pressure ulcers (PUs) or vascular leg ulcers. In a single-blinded randomised controlled trial (RCT) patients were randomly allocated to two groups and treated with either propylbetaine-polihexanide (PP) solution (Prontosan) or NS. Wounds were assessed using the Bates-Jensen wound assessment tool (BWAT). Assessments took place at inclusion (T0), day 7 (T1), day 14 (T2), day 21 (T3), and day 28 (T4). Outcomes were analysed using a two-tailed Student's t-test. A total of 289 patients were included. Both groups had similar demographics, clinical status, and wound characteristics. Data analysis showed statistically significant differences between T0 and T4 for the following outcomes: BWAT total score, p=0.0248; BWAT score for inflammatory items, p=0.03; BWAT scores for wound size reduction (p=0.049) and granulation tissue improvement (p=0.043), all in favour of PP. The assessment of pain did not show any significant difference between the two groups. The study results showed significantly higher efficacy of the PP solution versus NS solution, in reducing inflammatory signs and accelerating the healing of vascular leg ulcers and PUs. This evidence supports the update of protocols for the care of chronic wounds. The authors have no conflict of interest regarding this research. This is an investigator initiated trial. B. Braun Milano SpA kindly provided the material under investigation for both treatment groups, and paid the Ethics Committees' application fees in all participating centres.


Association between transforming growth factor-beta 1 polymorphism and virologic characteristics of chronic hepatitis C.
The production of transforming growth factor beta 1 (TGF-beta1) has been reported as being significantly associated with the gene polymorphism in the leader sequence at positions +29. The current study aimed to evaluate the associations between the polymorphism and the clinical characteristics of chronic hepatitis C (CHC). A total of 422 (252 men; mean age: 49.7 +/- 11.2 years) Taiwanese CHC patients with liver biopsies were enrolled. The TGF-beta1 gene polymorphism at position +29 (T or C), hepatitis C virus (HCV) RNA genotypes, and serum HCV RNA levels of these patients were determined. Of the 422 patients, the frequency of the T allele was 45.4%. Based on univariate analyses, a significantly lesser proportion of patients with allele T had high viral loads than those who were without allele T (P = 0.026). The lesser HCV RNA levels and HCV genotype 1b infection were significantly associated with the inheritance of the T allele in female patients based on univariate (P = 0.012 and 0.007, respectively) and multivariate regression (odds ratio/95% confidence interval: 0.434/0.219-0.859 and 0.468/0.237-0.927, respectively) analyses. In male patients with or without inheritance of the T allele, the clinical characteristics were similar. In conclusion, the association between TGF-beta1 polymorphism and virologic characteristics of chronic HCV infection implicated a significant role of host genetic factors on the clinical features of CHC. Female patients who carry T allele at position +29 were predisposed to be associated with HCV genotype non-1b infection and lesser HCV viral load, which revealed the gender effect.


Metabolic response assessment with 18F-FDG PET/CT: inter-method comparison and prognostic significance for patients with non-small cell lung cancer.
This study aimed to (1) compare the agreement of two evaluation methods of metabolic response in patients with non-small cell lung cancer (NSCLC) and determine their prognostic value and (2) explore an optimal cutoff of metabolic reduction to distinguish a more favorable subset of responders. This is a secondary analysis of prospective studies. Enrolled patients underwent 18F-PET/CT within 2 weeks before, during, and months after radiotherapy (post-RT). Metabolic response was assessed using both Peter MacCallum (PM) method of qualitative visual assessment and University of Michigan (UM) method of semiquantitative measurement. The agreement between two methods determined response, and their prediction of outcome was analyzed. Forty-four patients with median follow-up of 25.2 months were analyzed. A moderate agreement was observed between PM- and UM-based response assessment (Kappa coefficient = 0.434), unveiling a significant difference in CMR rate (p = 0.001). Categorical responses derived from either method were significantly predictive of overall survival (OS) and progression-free survival (PFS) (p < 0.0001). Numerical percentage decrease of FDG uptake also showed significant correlations with survival, presenting a hazard ratio of 0.97 for both OS and PFS. A 75 % of SUV decrease was found to be the optimal cutoff to predict OS and 2-year progression. There was a modest discrepancy in metabolic response rates between PM and UM criteria, though both could offer predictive classification for survival. The percentage decrease provides an ordinal value that correlates with prolonged survival, recommending 75 % as the optimal threshold at identifying better responders.


WITHDRAWN: Endosomal trafficking of EGFR regulated by hVps18 via interaction of MVB sorting machinery.
This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.


Prescribing patterns for paediatric hyperopia among paediatric eye care providers.
To survey paediatric eye care providers to identify current patterns of prescribing for hyperopia. Paediatric eye care providers were invited, via email, to participate in a survey to evaluate current age-based refractive error prescribing practices. Questions were designed to determine which factors may influence the survey participant's prescribing pattern (e.g., patient's age, magnitude of hyperopia, patient's symptoms, heterophoria and stereopsis) and if the providers were to prescribe, how much hyperopic correction would they prescribe (e.g., full or partial prescription). The response distributions by profession (optometry and ophthalmology) were compared using the Kolmogorov-Smirnov cumulative distribution function test. Responses were submitted by 738 participants regarding how they prescribe for their hyperopic patients. Most providers within each profession considered similar clinical factors when prescribing. The percentages of optometrists and ophthalmologists who reported considering the factor often differed significantly. Factors considered similarly by both optometrists and ophthalmologists were the presence of symptoms (98.0%, p = 0.14), presence of astigmatism and/or anisometropia (97.5%, p = 0.06) and the possibility of teasing (8.3%, p = 0.49). A wide range of prescribing was observed within each profession, with some providers reporting that they would prescribe for low levels of hyperopia while others reported that they would never prescribe. When prescribing for bilateral hyperopia in children with age-normal visual acuity and no manifest deviation or symptoms, the threshold for prescribing decreased with age for both professions, with ophthalmologists typically prescribing 1.5-2 D less than optometrists. The threshold for prescribing also decreased for both optometrists and ophthalmologists when children had associated clinical factors (e.g., esophoria or reduced near visual function). Optometrists and ophthalmologists most commonly prescribed based on cycloplegic refraction, although optometrists most commonly prescribed based on both the manifest and cycloplegic refraction for children ≥7 years. Prescribing patterns for paediatric hyperopia vary significantly among eye care providers.


An early account of gustatory sweating (Frey's syndrome): a chance observation 250 years ago.
Quite by chance, when reading an old manuscript dealing with fistulae of the parotid duct, the author came across a clear description of what is now well known as gustatory sweating (Frey's syndrome). The incident which gave rise to this observation is recalled and the account is reproduced in the original text.


Intrinsic mechanism for the removal of antibiotic pollution by a dual coagulation process from the perspective of the interaction between NOM and antibiotic.
Antibiotics bring potential risks to human health and ecosystem, and their coexistence with natural organic matters (NOMs) could have harmful impacts on the environment. Herein, a polyaluminium chloride (PAC)-polydimethyl diallyl ammonium chloride (PDMDAAC) dual coagulation process was designed to remove the co-pollutants of chlortetracycline (CTC) and humic acid (HA), representing antibiotics and NOMs, respectively. The main research strength was given to understand molecular interactions and their mechanisms associated with the coagulation and flocculation. We found that the co-existing HA and CTC increased the hydrophily and stability of contaminants, and generated HA@CTC complexes with large particles size. The interaction mechanism between CTC and HA was mainly hydrogen bonding, hydrophobic association action, n-π* electron donor-acceptor interaction, and π-π* conjugation. Lewis acid-base interaction was the main force between HA and CTC. The bonding energies of OH…N, OH…O, and hydrophobic association were -12.2 kcal/mol, -13.1 kcal/mol, and -11.4 kcal/mol, respectively, indicating that hydrogen bonding was stronger than hydrophobic association. The interactions between HA and CTC could improve their removal efficiency in the coagulation process. This is due to that the functional groups (COOH and OH) in the HA@CTC could be adsorbed by Al based hydrolysates. Polar interaction dominated the CTC and HA removal, and PAC was more efficient than PDMDAAC to remove HA@CTC complexes due to its higher complexing capacity. Thanks to the low concentration of residual contaminants and the formation of large and loose flocs, the interaction of HA and CTC could alleviate membrane fouling during ultrafiltration process. This study will provide new insight into the efficient removal of combined pollution and membrane fouling control.


TFE3-positive renal cell carcinoma occurring in three children with dysfunctional kidneys on immunosuppression.
Pediatric RCC is a rare pediatric neoplasm and is distinctly different compared to adult RCC, often demonstrating translocation morphology evidenced by unique histopathological features and TFE3 or TFEB nuclear expression. We report three cases of pediatric TFE3 positive RCC (TFE3-RCC) occurring in the setting of chronic kidney disease and long-term pharmacological immunosuppression, including two cases that developed in the native kidney following kidney transplantation. Together, these cases suggest that the kidney microenvironment in combination with immune dysregulation is likely contributing factors in the pathogenesis of some pediatric RCC, warranting further study. Long-term post-transplant surveillance may warrant screening for RCC.


Optimization of a Trap for Tuta absoluta Meyrick (Lepidoptera: Gelechiidae) and Trials to Determine the Effectiveness of Mass Trapping.
Management of the South American tomato leafminer, Tuta absoluta Meyrick, with insecticides has led to the widespread development of insect resistance. Mass trapping using traps baited with the female-produced sex pheromone is an attractive alternative for the management of this pest. The current study evaluated several commercial trap designs for capture of T. absoluta. Based on its small size and ease of handling, the most effective trap is a small plastic container with entry windows cut on the sides filled with motor oil over water. These traps are most effective when placed near ground level. Tests of septa containing 0.1 or 0.2 mg of the pheromone (95:5) E4, Z8-14Ac/E4,Z8,Z11-14Ac were slightly more attractive than septa loaded with 0.5, 1.0, or 2 mg during the first week of use, but the latter three loadings were slightly more attractive than the first two loadings after 9 weeks. Ideal trap baits were loaded with 0.5 mg of pheromone. Higher numbers of T. absoluta were captured near upwind borders of tomato fields suggesting that treatments against T. absoluta should be concentrated near upwind parts of fields. Comparisons of conventional insecticide treatment versus mass trapping to manage T. absoluta damage in three different test sites showed that even when initial captures in monitoring traps were high (>35 males trap(-1) day(-1)), mass trapping at 48 traps/ha reduced leaf damage more efficiently than conventional insecticide treatment. Based on the typical insecticide recommendations against T. absoluta, mass trapping is an economically viable alternative.


Correlation of serum immunoglobulin subclass concentrations with antibody responses of children to immunization with Haemophilus influenzae type b polysaccharide-pertussis vaccine.
Children less than 24 months of age respond poorly to immunization with the capsular polysaccharide of Haemophilus influenzae type b. Because human antibodies to polysaccharide antigens are relatively restricted to IgG2, a late-maturing subclass, we examined the relationship between serum subclass concentrations and anticapsular antibody responses of 41 healthy children, 9 to 38 months of age, following immunization with type b polysaccharide mixed with pertussis vaccine. Both total and IgG anticapsular antibody responses correlated significantly with preimmune serum concentrations of IgG2 but not with those if IgG1. This correlation was age dependent, however, and after the effect of age was removed by partial correlation, the correlation between anticapsular antibody responses and serum IgG2 concentrations was no longer significant. These findings indicate that the ability to respond to this vaccine coincides with maturation of the ability to secrete immunoglobulin of the IgG2 subclass; however, individual variation in IgG2 that is independent of age does not correlate with antibody response to the type b polysaccharide.


Radioanatomic Assessment of the Geniculate Ganglion Dehiscence and Dimension: A Cadaveric Study.
The main aim of this study placed on cadavers was to compare the data related to geniculate ganglion (GG) dehiscence and dimension obtained from computed tomography (CT) with dissection values. This study was conducted on 20 temporal bones obtained from 10 cadavers (4 female, 6 male) aged between 45 and 92 (71.50 ± 15.98) years. All the measurements related to GG dimension were performed with a CT scanner and microdissection. The size of GG including its area, length, and width did not show statistically significant differences in terms of sex, side, and assessment method (CT and cadaveric dissections). The dehiscent GG was observed in 6 (30%) and 5 (25%) out of 20 temporal bones in CT and cadaveric dissections, respectively. The presence and absence of GG dehiscence in CT and dissection were similar in 75%. Our findings based on dissection data suggest that radiologic evaluation of dehiscent GG detection might be erroneous by 25%, which highlights that surgeons should be careful when lifting the dura to prevent GG injury during middle cranial fossa surgical approaches. On the other hand, there was no statistical difference between CT and dissection measurements related to GG dimension.