Potentiometric membrane sensor based on 6-(4-nitrophenyl)-2,4-diphenyl-3,5-diaza-bicyclo[3.1.0]hex-2-ene for detection of Sn(II) in real samples.
A Sn2+ ion-selective electrode which was prepared with a polymeric membrane based on 6-(4-nitrophenyl)-2,4-diphenyl-3,5-diaza-bicyclo[3.1.0]hex-2-ene (NDDBH) as a ionophore. Effects of experimental parameters such as membrane composition, nature and amount of plasticizer, the amount of additive and concentration of internal solution on the potential response of Sn2+ sensor were investigated. The electrode exhibited a Nernstian slope of 28.8+/-1.1 mV/decade of Sn2+ over a concentration range of 1.0 x 10(-5) to 1.0 x 10(-1) M of Sn2+ in an acidic solution (pH 1). The limit of detection was 4.0 x 10(-6) M. The results show that this electrode can be used in ethanol media until 20% (v/v) concentration without interference. It can be used for more than 6 weeks without any considerable divergence in the potentials. The proposed membrane electrode revealed very good selectivity for Sn(II) ions over a wide variety of other cations and could be used in acidic media. The standard electrode potentials were determined at different temperatures and used to calculate the isothermal coefficient of the electrode. The stability constant (log K(s)) of the Sn(II)-ionophore complex was determined at 25 degrees C by potentiometric titration in mixed aqueous solution. It was used as indicator electrode in potentiometric determination of Sn(II) ion in real samples.


Spontaneous Cranial Bone Regeneration After a Craniectomy in an Adult.
Spontaneous reossification is a very rare phenomenon following a large calvarial defect, particularly in adults. A 29-year-old woman with acute subdural hematoma and brain edema underwent emergent decompressive craniectomy and evacuation of hematoma. Follow-up examination 2 years later showed a well-formed bone along the craniectomy site. To our knowledge, this is the first case report with total spontaneous reossification in adults. A literature review is provided, and the physiology of the process is suggested. Pericranium, diploë, and, above all, dura mater collaborate in spontaneous bone formation. All these layers are very important, and they must be respected during dissection.


Radionuclides as natural tracers of the interaction between groundwater and surface water in the River Andarax, Spain.
The identification of specific aquifers that supply water to river systems is fundamental to understanding the dynamics of the rivers' hydrochemistry, particularly in arid and semiarid environments where river flow may be discontinuous. There are multiple methods to identify the source of river water. In this study of the River Andarax, in the Southeast of Spain, an analysis of natural tracers (physico-chemical parameters, uranium, radium and radon) in surface water and groundwater indicates that chemical parameters and uranium clearly identify the areas where there is groundwater-surface water interaction. The concentration of uranium found in the river defines two areas: the headwaters with U concentrations of 2 μg L-1 and the lower reaches, with U of 6 μg L-1. Furthermore, variation in the 234U/238U isotopic ratio allowed us to detect the influence that groundwater from the carbonate aquifer has on surface water in the headwaters of the river, where the saline content is lower and the water has a calcium bicarbonate facies. The concentration of 226Ra and 222Rn are low in the surface waters: <1.6 × 10-6 μg L-1 and <5.1 × 10-12 μg L-1, respectively. There is a slight increase in the lower reaches where the water has a permanent flow, greater salinity and a calcium-magnesium-sulphate facies. All this is favoured by the influence of groundwater from the detritic aquifer on the surface waters. The results of this study indicate the utility in the use of physico-chemical and radiological data conjointly as tracers of groundwater-surface water interaction in semiarid areas where the lithology of aquifers is diverse (carbonate and detritic) and where evaporitic rocks are present.


Proteomics, photosynthesis and salt resistance in crops: An integrative view.
Salinity is a stressful condition that causes a significant decrease in crop production worldwide. Salt stress affects several photosynthetic reactions, including the modulation of several important proteins. Despite these effects, few molecular-biochemical markers have been identified and evaluated for their importance in improving plant salt resistance. Proteomics is a powerful tool that allows the analysis of multigenic events at the post-translational level that has been widely used to evaluate protein modulation changes in plants exposed to salt stress. However, these studies are frequently fragmented and the results regarding photosynthesis proteins in response to salinity are limited. These constraints could be related to the low number of important photosynthetic proteins differently modulated in response to salinity, as has been commonly revealed by conventional proteomics. In this review, we present an evaluation and perspective on the integrated application of proteomics for the identification of photosynthesis proteins to improve salt resistance. We propose the use of phospho-, thiol- and redox-proteomics, associated with the utilization of isolated chloroplasts or photosynthetic sub-organellar components. This strategy may allow the characterization of essential proteins, providing a better understanding of photosynthesis regulation. Furthermore, this may contribute to the selection of molecular markers to improve salt resistance in crops.


c-Fos expression following context conditioning and deep brain stimulation in the bed nucleus of the stria terminalis in rats.
Deep brain stimulation (DBS) in the bed nucleus of the stria terminalis (BST), a region implicated in the expression of anxiety, shows promise in psychiatric patients, but its effects throughout the limbic system are largely unknown. In male Wistar rats, we first evaluated the neural signature of contextual fear (N = 16) and next, of the anxiolytic effects of high-frequency electrical stimulation in the BST (N = 31), by means of c-Fos protein expression. In non-operated animals, we found that the left medial anterior BST displayed increased c-Fos expression in anxious (i.e., context-conditioned) versus control subjects. Moreover, control rats showed asymmetric expression in the basolateral amygdala (BLA) (i.e., higher intensities in the right hemisphere), which was absent in anxious animals. The predominant finding in rats receiving bilateral BST stimulation was a striking increase in c-Fos expression throughout much of the left hemisphere, which was not confined to the predefined regions of interest. To conclude, we found evidence for lateralized c-Fos expression during the expression of contextual fear and anxiolytic high-frequency electrical stimulation of the BST, particularly in the medial anterior BST and BLA. In addition, we observed an extensive and unexpected left-sided c-Fos spread following bilateral stimulation in the BST.


Surgical alternatives in the treatment of life-threatening ventricular arrhythmias.
We present our experience in the treatment of life-threatening ventricular tachycardia using electrophysiologically guided surgery (97 patients), automatic implantable cardioverter defibrillator (AICD) (42 patients), and orthotopic heart transplantation (15 patients). Eighty-three percent of these patients had ischemic and 17%, nonischemic heart disease. Our results of electrophysiologically directed surgery show an early mortality of 10% and a recurrence of 5% in the ischemic group. In the nonischemic group, the recurrence was 45%. The AICD was implanted in 31 patients with ischemic heart disease, in 5 with ventricular dysplasia, and in 6 with dilative cardiomyopathy, the ejection fractions ranging from 12% to 65%, with a mean of 30%. Early and late mortalities were 5% and 19%, respectively. The AICD was effective in all patients. Survival rate at 1 year was 83% +/- 6.4%. Thirteen of 15 patients have survived heart transplantation for 3-20 months (mean: 11 months). Ejection fractions prior to transplantation ranged from less than 10% to 34% (mean: 16%). We conclude that electrophysiologically guided surgery is highly effective in most cases of ischemia-related ventricular tachycardia. The AICD is considered a palliative alternative in patients with either poor ventricular function, no electrophysiological substrate, or multimorphological tachycardia. Heart transplantation has to be considered especially in young patients in whom progression of the underlying disease can be anticipated. Bridging by AICD is possible when transplantation is not immediately available or recommendable.


Sirolimus-associated acute respiratory distress syndrome in a renal transplant recipient.
Sirolimus is a new potent immunosuppressive drug used in organ transplantation; its major advantage is the absence of deterioration in renal function. Documented adverse effects include myelosuppression and hyperlipidemia. Recently several cases of sirolimus-associated interstitial pneumonitis have been reported, usually of mild severity. We report a new case that was complicated by a severe acute respiratory distress syndrome, which required several days of mechanical ventilation. No infectious or cardiogenic etiology was documented. Low sirolimus blood levels and acute CD4 lymphocytic alveolitis suggested an immune-related mechanism rather than a direct toxic effect of the drug. The patient recovered after discontinuation of sirolimus and the administration of corticosteroids.


Characterization of ultra-high affinity monoclonal antibodies with a dimeric, symmetrical antigen: inhibition of the receptor recognition site of nerve growth factor.
We generated a family of ultra-high affinity monoclonal antibodies (MAb) which inhibit competitively the binding of nerve growth factor (NGF) to its receptor. Preliminary experiments indicated that the dissociation constants (Kd) of some of the MAb:NGF complexes were substantially less than 0.1 nM. Conventional methods, such as ELISA and radioimmunoassays (RIA), were not sufficiently sensitive to measure the Kds of these MAb. Therefore, experimental conditions were developed to determine binding constants for these very high affinity MAb. The experiments establish that the Kds for our anti-NGF MAb range from 2.6 nM to 39 fM. Additionally, the inhibition of NGF binding to NGF-receptor by MAb is fully consistent with a purely competitive model but is not consistent with a model allowing the formation of a ternary complex of NGF, MAb, and NGF-receptor. One MAb, M4, immunoprecipitates NGF indicating interaction between each protomer of the NGF dimer and individual MAb molecules. We also evaluated the effects of mild denaturing conditions on the binding and biological activity of NGF and on recognition by the MAbs. Guanidine HCl or heat treatment of NGF resulted in only small, but significant, changes in binding or biological activity, in parallel with changes in recognition by the MAbs. However, binding, biological activity, and recognition by six of seven MAbs were completely eliminated by beta-mercaptoethanol reduction. Thus, our results are consistent with the MAbs interacting with the receptor recognition site on the surface of the NGF molecule. The high affinity MAbs will serve as sensitive probes of structural elements of NGF responsible for binding and biological activity.


The microstructure of cornea verticillata in Fabry disease and amiodarone-induced keratopathy: a confocal laser-scanning microscopy study.
The purpose of this study is to describe cornea verticillata in Fabry disease and in amiodarone-induced keratopathy and to compare the corneal microstructure of both types. Ten eyes from ten normal subjects, 28 eyes from 22 patients with Fabry disease confirmed by molecular genetic studies, and 16 eyes from 11 patients receiving amiodarone were examined by slit-lamp microscopy and in-vivo confocal laser-scanning microscopy (CLSM) with following three-dimensional reconstruction of the individual corneal layers. Five patients with Fabry disease were monitored during the course of enzyme replacement therapy (ERT). Evidence of cornea verticillata was found by slit-lamp microscopy both in patients with Fabry disease and in those with amiodarone-induced keratopathy; CLSM revealed the same pattern of hyper-reflective deposits in the basal cell layer of corneal epithelium in both sets of patients. Microdot changes in the anterior stroma were more prevalent in patients receiving amiodarone but do not presuppose the simultaneous presence of cornea verticillata. The bulbar conjunctiva was found to be normal in all patients. The tarsal conjunctival epithelium contained round hyper-reflective structures, which are also encountered physiologically, but these were more common in patients with Fabry disease. In one out of the five patients examined, monitoring of corneal changes over time during ERT disclosed a regressive tendency of the deposits in the epithelial basal cell layer documented by CLSM. The microstructural corneal changes typically seen in cornea verticillata in both Fabry disease and in amiodarone-induced keratopathy can be successfully visualized by confocal in-vivo microscopy at the level of the basal cell layer. By analogy, with the grading system for cornea verticillata based on slit-lamp microscopy, staging of these deposits in the basal cell layer can also be performed following in-vivo CLSM. The microdots in the anterior stroma as well as the changes observed in the tarsal conjunctiva should be regarded as having less diagnostic value because such changes may also occur in normal subjects. The utility of CLSM as a tool for monitoring ERT in Fabry disease over time needs to be confirmed in studies with larger sample sizes conducted over a longer period.


Investigating Factors Affecting Elderly's Intention to Use m-Health Services: An Empirical Study.
m-Health as an important part of e-health has recently become one of the most influential initiative in healthcare sector all over the world. In developing countries healthcare service providers started to provide m-health services from the last few years. Despite the widespread acceptance of mobile phones, the adoption of m-health among elderly is significantly low in developing countries. However, little research has been conducted to explore factors influencing elderly's intention to use m-health services particularly in developing countries. The objective of this study is to identify the factors that influence the elderly's intention to use m-health services. To assess elderly's intention to use m-health services, this study applied the Unified Theory of Acceptance and Use of Technology (UTAUT). Data were collected from participants of age 60 years and above. The partial least square method based on structural equation modeling was used to analyze data. The study found that performance expectancy, effort expectancy, social influence, and perceived credibility (p < 0.05) had significant influence on elderly's intention to use m-health services. However, facilitating condition (p > 0.05) had no significant influence on elderly's intention to use m-health services. The findings of this study may become beneficial for the governments, policy makers, and healthcare service providers in developing countries.


Diagnosis and immunocytochemical characterization of an EBV related diffuse B large cell lymphoma of the retroperitoneum from cell block preparations obtained by means of EUS guided FNA.
Diffuse large B cell lymphoma (DLBCL) in the retroperitoneum has been scarcely reported and the diagnostic workup is challenging due to difficulties in access to tissue. A 73-year-old female presented to the gastroenterology clinic, with recent-onset atypical abdominal pain and alternating constipation and diarrhea.


Penicillamine revisited: historic overview and review of the clinical uses and cutaneous adverse effects.
Penicillamine is a well-known heavy metal chelator, classically used in the treatment of Wilson disease, rheumatoid arthritis, and cystinuria. From a dermatologic standpoint, penicillamine was found to be useful in the treatment of systemic sclerosis. The successful therapeutic uses of penicillamine have been hindered by its numerous adverse effects, both cutaneous and extra-cutaneous. It is a unique drug since it provokes a diversity of dermatologic manifestations that include (1) acute hypersensitivity reactions, (2) dermopathies characterized by elastic fiber abnormalities including elastosis perforans serpiginosa and pseudo-pseudoxanthoma elasticum, (3) autoimmune disorders such as pemphigus and penicillamine-induced lupus erythematosus-like syndrome, and (4) miscellaneous dermatoses that result from undefined mechanisms. These cutaneous adverse effects may correlate with the dosage and duration of penicillamine therapy as well as the disease being treated.


Origin and dynamical behaviour of thermal protons in the Venusian ionosphere.
An important source of thermal H(+) and/or D(+) has been overlooked in the ionosphere of Venus which supports the choice of H(+) and/or D(+) as the dominant light ion at high altitudes.


Survival of monoblock RM vitamys compared with modular PINNACLE cups: mid-term outcomes of 200 hips performed by a single surgeon.
Monoblock cups have theoretical advantages over modular cups; however, their superiority in terms of survival has not been confirmed in comparative studies. We compared the mid-term survivorship of 107 RM Pressfit vitamys monoblock cups (Mathys Ltd., Bettlach, Switzerland) with 93 modular pressfit Pinnacle cups (DePuy Synthes, Warsaw, IN, USA). All cases were registered in the Arthroplasty Registry Thessaloniki and performed by a senior surgeon through the same approach between 2013 and 2014. The groups were comparable in sex distribution, preoperative diagnosis, follow-up, cup diameter, head diameter, type and use of screws, HOOS and HSS preop scores; the recipients of RM cup were significantly younger. 3 sockets were revised. The 6-year survival for any reason was 99.1% for the RM and 97.8 % for the PINNACLE group. There was no difference in survival for aseptic loosening and any reason between groups (log-rank test p = 0.921 and p = 0.483, respectively). The age (95% CI, 0.79-1.1), sex (95% CI, 0.2-45.0), cup diameter (95% CI, 0.18-1.1), head diameter (95% CI, 0.004-6.2), preoperative diagnosis and use of screws (95% CI, 0.02-4.3), did not influence hazard ratio for revision between groups. HHS and HOOS were comparable at the last follow-up. Our study demonstrated that both cup designs had similar revision rates at mid-term follow-up, regardless the fact that the RM vitamys was used in a cohort of younger patients; which according to the literature would have led to earlier failures. Further long-term data are needed to evaluate the superiority of RM vitamys in the clinical setting, especially in the young.


Long-term follow-up of congenital distal tibiofibular diastasis: a report of two female patients.
Congenital diastasis of the inferior tibiofibular joint is an extremely rare variant of dysplastic tibial anomaly, which is usually associated with significant shortening of the lower leg and ipsilateral foot deformity due to talus incarceration in the distal tibiofibular mortise. The purpose of this study was to present the long-term results of reconstructive treatment and the functional outcome after a follow-up of 11-16 years. The principles of extremity preservation and reconstruction with the Ilizarov frame have shown a stable ankle joint, a plantigrade foot, and fully independent outdoor ambulation in both patients at the final follow-up. We concluded that amputation should not be performed under this condition.


[Evolution of the obstetrical Shock Index in postpartum haemorrhage according to the use of sulprostone].
The Shock Index (SI) is used in emergency medicine to assess the severity of active bleeding and in the postpartum context for postpartum haemorrhage (PPH). We investigated the diagnostic value of haemodynamic parameters (SI, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP)) in predicting subsequent use of uterotonic sulprostone treatment. This was a retrospective study including parturients with PPH ≥ 500mL between January 2017 and December 2018. Hemodynamic parameters at the diagnosis of PPH were compared according to whether the patient required subsequent sulprostone treatment (sulprostone(+) group) or not (sulprostone(-) group). We included in the analysis 147 patients. The SI was significantly higher in the sulprostone(+) group (0.92±0.28 vs. 0.83±0.22; p=0.04). The SBP (107.2±17.5 vs. 113.8±17.7mmHg; p=0.03), DBP (56.8±12,2 vs. 61.5±13,2mmHg; p=0.04), MAP (73.6±12.6 vs. 78.5±13.4mmHg; p=0.03) were significantly lower in the same group. No difference between AUC of these parameters to predict the use of sulprostone was found (AUC between 0.59 and 0.61). No significant difference was found for the HR between the two groups. The diagnostic value of SI appeared to be low and similar to other haemodynamic parameters in predicting the use of sulprostone.


Evaluation of adalimumab biosimilar candidate (HS016) in Chinese patients with active ankylosing spondylitis based on a health survey: sub-analysis of a phase 3 study.
The equivalence of the biosimilar HS016 to adalimumab (Humira) for the treatment of active ankylosing spondylitis (AS) patients has been previously validated. The aim was to compare the efficacy of HS016 and adalimumab in stratified subgroups at different time points using Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) and short form 36 (SF-36) questionnaires. We carried out a multicenter, randomized, double-blind, parallel, positive control, phase 3 trial of patients with active AS. They were selected randomly to be subcutaneously administered 40 mg HS016 or adalimumab every 2 weeks for a total treatment period of 24 weeks in a 2:1 ratio. A health surveys were used to assess mental and physical improvements of patients as well as other factors. HAQ-S revealed that changes in scores from baseline in both groups were time dependent until 14 weeks and that during the first 4 weeks of treatment the changes declined rapidly. The SF-36 health survey revealed that both HS016 and adalimumab produced rapid beneficial effects against AS during the first 2 weeks of therapy, which gradually declined between 2 and 12 weeks and flattened out after 12 weeks until 24 weeks. This trial demonstrated that both HS016 and adalimumab produced rapid improvements in symptoms during the first 2 weeks of treatment. These findings suggest that HS016 is an alternative economical treatment for Chinese AS patients producing a rapid amelioration of symptoms, aiding them to recover their lifestyle satisfaction. http://www.chictr.org.cn/enindex.aspx , ChiCTR1900022520, retrospectively registered. Key points • HS016 and adalimumab produced rapid AS symptom improvements during the first 2 weeks followed by a slowdown of improvements until week 4 with afterwards few improvements evaluated by HAQ-S • The improvements according to the short form of the 36 (SF-36) questionnaires revealed similar trends as for HAQ-S • There was no significant difference in HAQ-S and SF-36 scores between HS016 and adalimumab.


Hypertension in a patient with Gitelman's syndrome.
Gitelman's syndrome is an autosomal recessive disorder characterized by sodium wasting and hypotension. A middle-aged woman was diagnosed with Gitelman's syndrome because of typical clinical manifestations in the youth and homozygous mutations of 18-base-pair insertion in exon 6 of thiazide-sensitive NaCl-cotransporter gene. It was unusual that she showed hypertension with advancing age. Her serum potassium levels remained low at around 3.5 mEq/l despite potassium supplementation. This case demonstrates that hypertension could result in spite of the extremely decreased sodium reabsorption in Gitelman's syndrome and that essential hypertension is genetically heterogeneous, and abnormality of all genes may not be necessarily required to cause blood pressure rise.


Large adrenocortical adenoma with malignant features on imaging: A case report.
Large adrenocortical adenomas have rarely been reported. We describe a case of a 26-year-old man who underwent an adrenalectomy for a large adrenocortical adenoma (8.6 × 7.7 cm). Although the lesion had typical malignant features on imaging, histopathological examination revealed an adrenocortical adenoma. This highlights that imaging alone may not be able to distinguish adrenocortical carcinomas from adrenal masses. In most cases, a resection should be performed for early diagnosis and management of large adrenal masses with malignant features on imaging. To our knowledge, this is the first report of a large adrenocortical adenoma diagnosed with multiple imaging investigations.


Effects of eluent temperature and elution bandwidth on detection response for aerosol-based detectors.
Aerosol detectors provide generally uniform response for most analytes, independent of their optical properties, and have the advantage of being compatible with elevated temperature mobile phases. Therefore, aerosol detectors present an attractive detection alternative for high temperature liquid chromatography (HTLC) separations. The present study has investigated the effects of HTLC conditions using aqueous mobile phases on the detection response of an evaporative light-scattering detector (ELSD) and a corona-charged aerosol detector (C-CAD). The response of the ELSD was increased up to 5-fold by increasing the separation temperature from 30°C to 180°C. The C-CAD showed much smaller increases in response under the same conditions. This increase in response was found not to result from the increased temperature for the mobile phase but rather from compression of the elution bandwidth at elevated temperature. The effect of bandwidth on detector response was confirmed using flow-injection studies in which the same amount of analyte was introduced into the detector at varying bandwidths. Furthermore, it is shown that a temperature gradient can be used to counteract the effects of varying bandwidths associated with isocratic-isothermal separations, with relatively constant bandwidth and detector response being observed with appropriate temperature gradients. This study demonstrates the necessity to consider the elution bandwidth in HTLC-aerosol detector analysis.


A survey of image processing techniques and statistics for ballistic specimens in forensic science.
This paper provides a review of recent investigations on the image processing techniques used to match spent bullets and cartridge cases. It is also, to a lesser extent, a review of the statistical methods that are used to judge the uniqueness of fired bullets and spent cartridge cases. We review 2D and 3D imaging techniques as well as many of the algorithms used to match these images. We also provide a discussion of the strengths and weaknesses of these methods for both image matching and statistical uniqueness. The goal of this paper is to be a reference for investigators and scientists working in this field.


Intact parathyroid hormone levels and primary hyperparathyroidism.
The aim of this article is to compare clinical characteristics and lab values for metabolic syndrome between primary hyperparathyroidism (PHPT) patients with different levels of serum intact parathyroid hormone (iPTH) and to determine correlation between different clinical characteristics among PHPT patients Methods: We reviewed charts of 212 PHPT patients in this retrospective study. Patients were divided into two groups according to their initial serum iPTH levels. Student's t-tests were used to compare the two groups for differences in clinical characteristics and laboratory values. Pearson's correlation coefficients were used to assess associations. Of the 212 PHPT patients, 100 were classified as m-iPTH group (serum iPTH < 140 pg/mL), whereas 112 patients were defined as h-iPTH group (serum iPTH ≥ 140 pg/mL). The h-iPTH patients were younger, had higher serum calcium and alkaline phosphatase levels, but exhibited lower 25(OH)-vitamin D and HDL levels, when compared with those of m-iPTH patients. Adenoma weights in the h-iPTH group tended to be higher than that in the m-iPTH group. Furthermore, association studies revealed that the iPTH level was positively correlated with adenoma weight and serum calcium and triglyceride (TG) levels but negatively correlated with HDL level. Our study supports the hypothesis that iPTH level is associated with TG and HDL levels and should be a factor to consider in the management of PHPT patients.


Explanatory signal interpretation and metabolite identification strategies for nominal mass FIE-MS metabolite fingerprints.
Flow injection electrospray mass spectrometry (FIE-MS) metabolite fingerprinting is widely used as a 'first pass' screen for compositional differences, where discrimination between samples can be achieved without any preconceptions. Powerful data analysis algorithms can be used to select and rank FIE-MS fingerprint variables highly explanatory of the biological problem under investigation. We describe how to create a species-specific FIE-MS/MS(n) metabolite database and how to then query the database to predict the identity of highly significant variables within FIE-MS fingerprints. The protocol details how to interpret m/z signals within the explanatory variable list based on a correlation analysis in conjunction with an investigation of mathematical relationships regarding (de)protonated molecular ions, salt adducts, neutral losses and dimeric associations routinely observed in FIE-MS fingerprints. Although designed for use by biologists/analytical chemists, collaboration with data-mining experts is generally advised. The protocol is applicable in any areas of bioscience research involving FIE-MS fingerprinting.


Changes in the Expression of Various Transporters as Influencing Factors of Resistance to Cisplatin.
Changes in the expression of transporters have been reported as factors in resistance to cisplatin (CDDP). This study was designed to clarify whether CDDP-resistant strains isolated from a cell line had the same characteristics, and whether these characteristics could be therapeutic targets. Intracellular platinum levels were determined by the inductively-coupled plasma method. mRNA expression levels were determined using the real-time polymerase chain reaction. Some CDDP-resistant HepG2 cell lines exhibited changes in the expression of copper transporter 1, multidrug resistant protein (MRP)2, and/or MRP3, resulting in decreased intracellular platinum amounts, while others showed no change in platinum accumulation. Expression of these transporters was not necessarily maintained in a constant direction within the cell population isolated from the same origin. These results suggest that the CDDP-resistant tumors caused by a decrease in intracellular platinum content consist of a heterogeneous cell population showing expression changes of several transporters.


Enhanced spin-phonon-electronic coupling in a 5d oxide.
Enhanced coupling of material properties offers new fundamental insights and routes to multifunctional devices. In this context 5d oxides provide new paradigms of cooperative interactions that drive novel emergent behaviour. This is exemplified in osmates that host metal-insulator transitions where magnetic order appears intimately entwined. Here we consider such a material, the 5d perovskite NaOsO3, and observe a coupling between spin and phonon manifested in a frequency shift of 40 cm(-1), the largest measured in any material. The anomalous modes are shown to involve solely Os-O interactions and magnetism is revealed as the driving microscopic mechanism for the phonon renormalization. The magnitude of the coupling in NaOsO3 is primarily due to a property common to all 5d materials: the large spatial extent of the ion. This allows magnetism to couple to phonons on an unprecedented scale and in general offers multiple new routes to enhanced coupled phenomena in 5d materials.


Surfactant treatment may accelerate epithelial cell regeneration in hyaline membrane disease of the newborn.
Previous studies of histologic changes in the lungs of infants with hyaline membrane (HMD) disease of the newborn treated with surfactant have focused on the occurrence of hemorrhage and bronchopulmonary dysplasia (BPD). Observations in autopsied infants with HMD suggested a possible acceleration of epithelial cell regeneration in those receiving surfactant. We studied lungs of the 11 autopsied infants with HMD treated with surfactant, who survived less than 1 week, and compared them to 22 infants with HMD not given surfactant. Epithelial cell regeneration, BPD, and airway and interstitial hemorrhage were graded on a 0-to-3 scale. Treated infants showed significantly more epithelial cell regeneration (p<0.05) and airway hemorrhage (p<0.05). Also, treated infants showed recognizable epithelial regeneration 1 day earlier than the nontreated group. The study supports the observation that regeneration of the necrotic respiratory epithelium of HMD is accelerated in infants treated with surfactant.


Factors affecting articulation skills in children with velocardiofacial syndrome and children with cleft palate or velopharyngeal dysfunction: a preliminary report.
To examine the influence of speech perception, cognition, and implicit phonological learning on articulation skills of children with velocardiofacial syndrome (VCFS) and children with cleft palate or velopharyngeal dysfunction (VPD). Cross-sectional group experimental design. Eight children with VCFS and five children with nonsyndromic cleft palate or VPD. All children participated in a phonetic inventory task, speech perception task, implicit priming nonword repetition task, conversational sample, nonverbal intelligence test, and hearing screening. Speech tasks were scored for percentage of phonemes correctly produced. Group differences and relations among measures were examined using nonparametric statistics. Children in the VCFS group demonstrated significantly poorer articulation skills and lower standard scores of nonverbal intelligence compared with the children with cleft palate or VPD. There were no significant group differences in speech perception skills. For the implicit priming task, both groups of children were more accurate in producing primed nonwords than unprimed nonwords. Nonverbal intelligence and severity of velopharyngeal inadequacy for speech were correlated with articulation skills. In this study, children with VCFS had poorer articulation skills compared with children with cleft palate or VPD. Articulation difficulties seen in the children with VCFS did not appear to be associated with speech perception skills or the ability to learn new phonological representations. Future research should continue to examine relationships between articulation, cognition, and velopharyngeal dysfunction in a larger sample of children with cleft palate and VCFS.


Emerging mass spectrometry-based technologies for analyses of chromatin changes: analysis of histones and histone modifications.
Mass spectrometry (MS) is rapidly becoming an indispensable tool for the analysis of posttranslational modifications (PTMs) of proteins, and particularly histone PTMs that regulate physiological processes. The more traditional bottom-up approach of searching for modifications on peptides rather than intact proteins (top-down) has proven useful for finding phosphorylation, acetylation, and ubiquitination sites. With the use of modern instrumentation and various MS-based techniques, peptides and their PTMs can be characterized in a high-throughput manner while still maintaining high sensitivity and specificity. In complement to bottom-up MS, recent advances in MS technology, such as high-field Fourier transform ion cyclotron resonance (FTICR)-mass spectrometry, have permitted the study of intact proteins and their modifications. On-line and off-line protein separation instruments coupled to FTICR-MS allow the characterization of PTMs previously undetectable with bottom-up approaches. The use of unique fragmentation techniques in FTICR-MS provides a viable option for the study of labile modifications. In this chapter, we provide a detailed description of the analytical tools - mass spectrometry in particular - that are used to characterize modifications on peptides and proteins. We also examine the applicability of these mass spectrometric techniques to the study of PTMs on histones via both the bottom-up and top-down proteomics approaches.


Characteristics and impact of theory of planned behavior interventions on smoking behavior: A systematic review of the literature.
Theoretical frameworks such as the theory of planned behavior (TPB) can be applied to design and evaluate smoking behavior interventions. The present systematic review aimed to: (i) determine the characteristics of TPB-based interventions and their reported impact on smoking behavior and TPB variables, (ii) evaluate the level of methodological quality in the included studies, and (iii) assess the quality of the theoretical implementation. Studies were eligible for inclusion if the intervention targeted smoking behavior, was explicitly based on the TPB, and if smoking behavior or intention was measured at least at post-intervention. Relevant articles were identified through searches on databases and internet search engines, responses to messages sent on thematic forums, consultation of prominent authors, and manual searches on key websites and key TPB-publications. Seventeen studies met the inclusion criteria. A majority of studies (65%) targeted the student population (i.e., elementary school, high school, university). Interventions minimally included the provision of health messages. The proportion of studies that reported a significant impact on smoking behavior, intention, attitude, subjective norm, or PBC ranged between 42% and 50%. Regarding methodological quality, unclear or high risks of bias were notably found regarding the selection of participants, data collection methods, withdrawal and drop-outs, and blinding. Regarding theoretical implementation, the reciprocal link between intervention techniques and TPB variables targeted remain unclear for a majority of studies. To better inform tobacco prevention and TPB research, future studies should more systematically use rigorous methods when designing, implementing, and reporting TPB-based interventions.


The role of physician networks in the diffusion of clinical applications of computers.
This study utilizes network analysis to examine the process by which physicians adopt and utilize computers in providing patient care. It also demonstrates how network techniques can be used to determine the role and position of individual physicians in their professional network and to develop educational programs designed to increase the clinical use of computers.


Estrogen and progesterone receptor levels in nonneoplastic breast epithelium of breast cancer cases versus benign breast biopsy controls.
Previous studies and biological mechanisms of carcinogenesis suggest that the steroid receptor content of benign breast epithelium may be related to breast cancer risk. The objective in this study was to compare the levels of estrogen receptor-alpha (ER) and progesterone receptor (PR) in nonneoplastic breast epithelium between breast cancer cases and biopsy controls. Between 1995 and 1997 at two sites (Women's College Hospital in Toronto and Kingston General Hospital), 667 women who were scheduled for diagnostic excisional breast biopsies completed a questionnaire providing personal information and agreed to allow analysis of routinely resected tissue. Histological slides with nonneoplastic epithelium were available for 101 cancer cases and 200 biopsy controls in Toronto and for 105 cancer cases and 119 controls in Kingston. Nonneoplastic epithelium was examined with immunohistochemical assays to determine the percent of epithelial cells staining for ER and PR. Unconditional logistic regression was used to calculate odds ratios (OR) stratified by study site. The ER content of nonneoplastic tissue was higher in cases than biopsy controls in unadjusted analyses; after adjustment for age, however, a weak association remained in only one of the study sites. After adjustment for age, the PR content of nonneoplastic tissue was slightly lower in breast cancer cases than controls in one study site. Furthermore, this inverse association was confined to women with PR negative breast cancer in comparison to the controls. No interaction between ER and PR content of nonneoplastic tissue was observed in relation to the odds of having breast cancer. The results of this study are consistent with only a slight indication of increased ER levels in nonneoplastic tissue in breast cancer cases relative to controls. This study contributes to the understanding of breast cancer by examining both ER and PR in nonneoplastic tissue. Limitations remain, however, such as the necessity of using as controls women with benign breast changes, difficulties in selecting the appropriate tissue for analysis, and tissue sampling concurrent to diagnosis.


Measuring the intensity of rural livelihood diversification strategies, and Its impacts on rural households' welfare: Evidence from South Gondar zone, Amahara Regional State, Ethiopia.
In Ethiopia, rural households are under risk in the sustainability of sources of income and forced to involve in diversified livelihoods because of the uncertain nature of the agricultural sector. Therefore, the aim of the study is to measure the livelihood diversification strategies and its impacts on rural households' welfare. The study used cross-sectional data, which is quantitative and qualitative in nature. Through the multistage sampling technique, the study selected 398 samples from the south Gondar zone. The data was analyzed through descriptive statistics, and Tobit and multiple linear regression models. The descriptive statistics analysis showed that income from crop and livestock productions are the most important contributors (97.74%) to livelihood diversification in the study area. The Simpsons Index of Diversity is (0.4) showing that there is a lower livelihood diversification in the study area. The Tobit model regression results showed that education, family size, irrigation, soil conservation, extension service, livestock, and infrastructure facility affect the intensity of livelihood diversification. Furthermore, the multiple regression result revealed that livelihood diversification has a positive impact on the welfare of rural households. The study concludes that to improve the livelihood and welfare of rural households, diversified livelihood strategies should be enhanced by facilitating farm activities through access to inputs, irrigation schemes, and infrastructure and off-farm activities. This article applied the Simpsons Index of Diversity (SID) to estimate the intensity of income diversification.• The method helps to measure the amount of diversified income and its effect on the welfare of rural dwellers. • The study helps to identify the common livelihood strategies and their relevance to improving rural living style.


Improving the detection of subscapularis tears using a specific transverse CT arthrography image.
The prevalence of subscapularis (SSC) tendon tears is often underestimated. This negatively impacts the shoulder function because the SSC muscle is a powerful internal rotator. The primary aim of this study was to compare a blended clinical and radiological preoperative index of suspicion for SSC tears to the arthroscopic findings. The secondary aim was to compare the surgeon's and radiologist's index of suspicion to determine which is more accurate. Analyzing a transverse image passing under the tip of the coracoid process, in combination with clinical examination, will be the standard for detecting SSC tears. This prospective study enrolled 50 consecutive patients who underwent shoulder arthroscopy. Preoperatively, four clinical tests were doneto detect SSC tears: lift-off, internal rotation lag sign, bear-hug, belly-press. A CT arthrography slice passing under the coracoid process tip was analyzed by the surgeon. The surgeon deduced a radiological index of suspicion for SSC tears then a blended clinical and radiological index of suspicion based on the clinical examination. Lastly, the surgeon looked at the radiologist's findings and index of suspicion for a lesion. The three indexes of suspicion were compared with the actual arthroscopy findings. The surgeon's blended clinical and radiological index of suspicion was similar to his radiological index. Both of the surgeon's indexes of suspicion were higher than the radiologist's. The prevalence of SSC tears was 58 %. We recommend doing multiple clinical tests as they complement each other in detecting SSC tears, since each one activates a different portion of the muscle. We advise surgeons to supplement their clinical examination by analyzing a specific image of the tendon below the coracoid, as the reference view for the starting point of SSC tears. IV, prospective diagnostic study on consecutive patients.


Toxicity of selected cationic drugs in retinoblastomal cultures and in cocultures of retinoblastomal and retinal pigment epithelial cell lines.
Tamoxifen and toremifene are antiestrogenic drugs successfully used in the therapy of breast cancer. Rheumatoid arthritis and malaria have been treated with chloroquine for decades. Unfortunately, tamoxifen and chloroquine are reported to induce retinal changes as a side effect. We now studied the effects of tamoxifen, toremifene, and chloroquine on the viability of the human retinoblastomal cell line Y79, using the WST-1 test or measurement of the cellular ATP content. The studies were made on Y79 cell cultures and on cocultures of Y79 cells and retinal pigment epithelial cell line ARPE-19. The cocultures were used to clarify the effect of retinal pigment epithelium on toxicity to Y79 cells. In the coculture, the drugs were applied to ARPE-19 cells growing in the culture inserts on top of Y79 cells and the viability of ARPE-19 and Y79 cells was assessed separately. Tamoxifen, toremifene, and chloroquine reduced dose-dependently the viability of Y79 cells after 24-h exposure. The ARPE-19 cells proved to be protective after chloroquine exposure in the coculture. The results shed light on the toxicity of tamoxifen and chloroquine in Y79 cells in vitro. With the coculture we were able to simulate the in vivo route of chloroquine to the retina via the retinal pigment epithelium.


Oncostatin M stimulates tissue inhibitor of metalloproteinase-1 via a MEK-sensitive mechanism in human myofibroblasts.
We previously showed that in cultured human myofibroblasts (hMFBs), Oncostatin M (OSM)-stimulated collagen accumulation is associated with increased tissue inhibitor of metalloproteinase (TIMP)1 message. However, the mechanism is unknown. hMFBs were isolated by outgrowth from cirrhotic liver explants and cultured. Using OSM (10 ng/ml) stimulation, with and without PD98059 (PD, a specific mitogen-activated protein kinase/extracellular signal-related kinase (MEK) inhibitor), we measured: TIMP-1 protein in culture medium by Western blot, TIMP-1 mRNA levels and stability by Northern analysis, TIMP-1 promoter activity (including transcription site mutation analysis), DNA binding activity to nuclear proteins by electrophoretic mobility shift assay (EMSA), and total and phosphorylated MAP kinase in hMFB extracts by Western blot. OSM stimulation of hMFBs increased TIMP-1 protein production 1.69-fold, TIMP-1 mRNA levels 2.36-fold, promoter activity 2.22-fold, TIMP-1 message stability, and phosphorylation of mitogen-activated protein kinase (MAPK). PD inhibited OSM-mediated stimulation of TIMP-1 protein, mRNA, promoter activity, phosphorylation of MAPK, and TIMP-1 message stability. An SP-1 transcription site of the TIMP-1 promoter is essential for OSM induction of TIMP-1 promoter activity. EMSA demonstrates that this site binds to transcriptional factors SP-1 and SP-3. OSM stimulates the TIMP-1 axis in hMFBs in vitro via a MEK-MAP kinase cascade.


Autophagy in Plant Immunity.
The highly conserved catabolic process of autophagy delivers unwanted proteins or damaged organelles to vacuoles for degradation and recycling. This is essential for the regulation of cellular homeostasis, stress adaptation, and programmed cell death in eukaryotes. In particular, emerging evidence indicates that autophagy plays a multifunctional regulatory role in plant innate immunity during plant-pathogen interactions. In this review, we highlight existing knowledge regarding the involvement of autophagy in plant immunity, mechanisms functioning in the induction of autophagy upon pathogen infection, and possible directions for future research.


Maternal diet and fatty acid pattern of breast milk.
The effect of habitual maternal diet on the fatty acid composition of breast milk was evaluated by conducting a dietary survey of lactating mothers and by analyzing their breast milk samples. The mean energy intake of the mothers was 9.8 MJ during the first survey week (20 mothers, 6-8 weeks post partum) and 8.6 MJ during the second survey week (13 mothers, 17-22 weeks post partum). Protein, fat and carbohydrate intake comprised 16%, 39% and 45% of the total energy intake, respectively. The breast milk samples contained 3.8% fat. Half of the fatty acids of the diets and breast milk were saturated (S), and one third were monoenoic. Polyunsaturated (P) fatty acids comprised 15% in the diets and 13% in the breast milk. The average P/S ratio was 0.3 both in the diets and breast milk samples. Carbohydrate intake correlated negatively (p less than 0.05) with arachidic acid of breast milk, and both protein and fat intakes correlated positively (p less than 0.05) with palmitic acid of breast milk. The maternal diet had no effect on the total fat content of breast milk. A positive correlation was found between the saturated (p less than 0.05) and polyunsaturated (p less than 0.01) fatty acids of maternal diet and breast milk. As to the single fatty acids, the only significant correlation was found with linoleic acid (p less than 0.01). However, the variation of linoleic acid intake explained only about 27% of the variation occurring in the breast milk.


Regulation of megakaryocytes in W/Wv mice.
W/Wv mice were injected with antiplatelet serum to produce thrombocytopenia or with platelet transfusions to induce thrombocytosis. The responses of their platelets and megakaryocytes were followed to determine if proliferative abnormalities of the megakaryocytic system would be detected. W/Wv mice responded normally to the stimulation from thrombocytopenia with rebound thrombocytosis, macromegakaryocytosis, and macrothrombocytosis. The megakaryocytes of these mice became smaller than normal in response to post-thrombocytopenic rebound thrombocytosis but not to transfusion-induced thrombocytosis. Thus, endogenous thrombocytosis appeared to be a more potent suppressor of megakaryocyte growth than exogenous. These results failed to reveal an effective abnormality of the thrombocytopoietic regulatory system of W/Wv mice in spite of their intrinsically reduced numbers of megakaryocytes and the well known defect of stem cell proliferation. Thrombocytopoietic regulation appeared, therefore, to occur mainly at the committed, rather then pluripotential, stem cell level, and normal responses of the platelet system were observed in spite of severe abnormalities at the pluripotential stem cell level.


Data on the current state of modular systems in a highly dynamic environment: Empirical analyses in the manufacturing industry and automotive industry of Germany.
Today, many companies develop modular systems to realise considerable product differentiation and variation while simultaneously reducing costs through economies of scale [1]. Designing these modular systems to be lasting and robust in a highly dynamic environment [2], avoiding subsequent modification cost [3,4] and staying innovative over the product lifecycle is crucial for sustainable success in an increasingly competitive market [5]. Two closely related surveys were carried out on the initial situation described above. The first survey deals with the major conflict between planning reliability and flexibility with regard to future boundary conditions that the described challenges lead to. The data presented in this article on the first survey was collected from German companies, mainly from the automotive industry, developing and manufacturing complex products using modular systems. Other represented companies operate in the machine and plant construction industry. The survey comprises the answers of 39 participants, gathered via online questionnaire. The 17 questions of the survey are divided into two topics: characteristics of the participants, and the problem description of modular systems in highly dynamic environments and the management thereof. The second survey deals with the anticipation of innovations in the design of modular systems and the selection of the right choice from a variety of possible innovations to be considered. The data presented in this article on the second survey was collected from German automotive manufacturers, which develop and manufacture complex products using modular systems. The survey comprises the answers of 501 participants, gathered via online questionnaire. The 14 questions of the survey are divided into two topics: characteristics of the participants, and the problem description of modular systems and the management thereof. The data obtained allows the identification of existing deficits and dedicated research on solutions.


Food intake control in birds.
The regulation of food intake has been a topic of intense investigation for several decades. Most investigators have used the rat in such studies while considerably fewer studies have been conducted using birds. Research concerned with the control of food intake in birds is discussed herein. In most instances, birds and mammals have similar control mechanisms. The alimentary tract and the liver are peripheral structures which function in the control of feeding in birds but much remains to be studied as to their role. Many brain loci, including the lateral hypothalamus, ventromedial hypothalamus, striatum and olfactory bulbs are also involved in controlling food intake. Studies with birds have revealed marked breed and line differences in the response to factors modulating food intake. The bird appears to provide an excellent model for studies designed to investigate how selection for growth can alter the mechanisms involved in food intake control.


Four-base codon/anticodon strategy and non-enzymatic aminoacylation for protein engineering with non-natural amino acids.
Techniques for position-specific incorporation of non-natural amino acids in an in vitro protein synthesizing system are described. First, a PNA-assisted non-enzymatic tRNA aminoacylation with a variety of natural and non-natural amino acids is described. With this technique, one can aminoacylate a specific tRNA simply by adding a preformed amino acid activated ester-PNA conjugate into an in vitro protein biosynthesizing system. Second, the genetic code is expanded by introducing 4-base codons that can be exclusively translated to non-natural amino acids. The most advantageous point of the 4-base codon strategy is to introduce multiple amino acids into specific positions in single proteins by using mutually orthogonal 4-base codons and orthogonal tRNAs. An easy and quick method for preparation of tRNAs possessing 4-base anticodons is also described. Combination of the non-enzymatic aminoacylation and the 4-base codon/anticodon strategy gives an easy and widely applicable technique for incorporating a variety of non-natural amino acids into proteins in vitro.


Anaerobic fermentation treatment improved Cd2+ adsorption of different feedstocks based hydrochars.
Hydrothermal carbonization technology has attracted wide attention in recent years owing to its advantages, e.g., high yield and clean production, compared with traditional pyrolysis. Anaerobic fermentation (AF) is a new method to modify carbon materials, which may improve the surface properties of hydrochar (HC). To explore whether AF has effects on different feedstocks based HCs, two kinds of HCs derived from wheat straw and poplar sawdust were treated with AF for different time in this study. By comparing the changes in physicochemical properties of anaerobic fermentative hydrochars (AFHCs), adsorption behaviors of Cadmium (Cd2+) on AFHCs were evaluated. The results showed that the surface electrical characteristics, specific surface area, and oxygen-containing functional groups of HCs improved significantly after AF treatment, which confirmed our hypothesis that AF is suitable for improving the adsorption of different feedstocks based HCs. The adsorption capacity of Cd2+ on AFHCs was significantly enhanced by a 3.1-3.4 times increase after AF treatment. The effect of AF treatment on wheat straw hydrochar (WHC) was more evident than poplar sawdust hydrochar (SHC). WHCs treated with AF own higher adsorption capacity of Cd2+, which was attributed to the higher negative charge, more exchangeable cations, and more oxygen-containing functional groups. The adsorption process was found to be a spontaneous endothermic reaction dominated by chemisorption and controlled by electrostatic attraction, ion exchange, functional groups complexation, and π-bonding coordination. These results were contributed to understanding the modification of HC by AF and its application in heavy metal pollution remediation.


Screening for depressive symptoms: validation of the center for epidemiologic studies depression scale (CES-D) in a multiethnic group of patients with diabetes in Singapore.
We determined the reliability and validity of the Center for Epidemiologic Studies Depression Scale (CES-D) against the DSM-IV-based diagnostic inventory, Schedule for Clinical Assessment in Neuropsychiatry (SCAN), in a multiethnic sample of adult subjects with diabetes attending a diabetes center in Singapore. A total of 522 subjects (74.7% Chinese, 11.1% Malay, and 14.2% Indian) completed culturally adapted versions of the CES-D; 291 subjects were administered the SCAN inventory. The CES-D (cutoff score 16) showed high negative predictive values of more than 90% in all three ethnic groups. The prevalence of depressive symptoms (CES-D) and depression (SCAN) was significantly different between the Chinese and Indian subjects (CES-D 27.4 vs. 43.2%, P = 0.006); (SCAN 15.0 vs. 31.1%, P = 0.01). The CES-D proved to be a reliable instrument for identifying patients with depressive symptoms in the multiethnic setting of this study.


Predicting prognosis in gastroentero-pancreatic neuroendocrine tumors: an overview and the value of Ki-67 immunostaining.
Gastroenteropancreatic neuroendocrine tumors (GEP-NETS) are unusual and rare neoplasms for which prognostic assessment and the diagnosis of malignancy, on the basis of histology alone, represent considerable challenges for the pathologist. To date, many molecular markers have been identified with a view to providing accurate and timely prediction of response to treatment and long-term survival. Proliferation remains a key feature of tumor progression, which has been widely estimated by the immunohistochemical use of the Ki-67 nuclear antigen. Given the continued difficulties inherent in prediction of malignancy in pancreatic neuroendocrine tumors (PETs) in particular, it has become unclear whether Ki-67 is truly a reliable prognostication marker. This review seeks to better establish what the consensus is on the role of the Ki-67 proliferation index as a prognostic indicator of long-term outcome in pancreatic neuroendocrine tumors. We conclude that most studies favor the utility of the Ki-67 proliferation index despite different critical percentages and in concert with other pathological parameters in the routine work-up of PETs.


Close distal margin and rectal cancer recurrence after sphincter-preserving rectal resection.
Negative surgical margins are important for local control of rectal cancer treated with sphincter-preserving surgery. However, the association of rectal cancer recurrence with close distal margin is not well established. Data were extracted from a prospective database of patients collected between 1991 and 2003. Included were 627 patients who underwent curative low anterior resection with total mesorectal excision for rectal cancer 2 to 12 cm from the anal verge. Three hundred ninety-nine patients received neoadjuvant therapy, 65 received postoperative adjuvant therapy alone, and 163 were treated with surgery alone. Median follow-up was 5.8 years. On multivariable analysis, overall recurrence was associated with pathologic stage, lymphovascular invasion, and distal margin. Mucosal recurrence was uncommon; only 16 events were recorded, and of those only 8 were at the initial site of isolated tumor recurrence; 7 of the 8 were surgically salvaged. On univariable analysis, mucosal recurrence was associated with close distal margin (5 vs 2% at 5 y) and lymphovascular invasion (7 vs 2%). Pelvic recurrence, other than isolated mucosal recurrence, was associated with distal location (6 vs 4% at 5 y) and lymphovascular invasion (11 vs 4%). Distal margin as a continuous variable was associated with overall recurrence (excluding isolated mucosal recurrence). Close distal resection margin identifies patients with increased risk of mucosal and overall cancer recurrence. Although neither causality nor a minimally acceptable margin length can be defined, the data support the importance of achieving a clear distal resection margin in the surgical management of rectal cancer.


Chlorophylls d and f and Their Role in Primary Photosynthetic Processes of Cyanobacteria.
The finding of unique Chl d- and Chl f-containing cyanobacteria in the last decade was a discovery in the area of biology of oxygenic photosynthetic organisms. Chl b, Chl c, and Chl f are considered to be accessory pigments found in antennae systems of photosynthetic organisms. They absorb energy and transfer it to the photosynthetic reaction center (RC), but do not participate in electron transport by the photosynthetic electron transport chain. However, Chl d as well as Chl a can operate not only in the light-harvesting complex, but also in the photosynthetic RC. The long-wavelength (Qy) Chl d and Chl f absorption band is shifted to longer wavelength (to 750 nm) compared to Chl a, which suggests the possibility for oxygenic photosynthesis in this spectral range. Such expansion of the photosynthetically active light range is important for the survival of cyanobacteria when the intensity of light not exceeding 700 nm is attenuated due to absorption by Chl a and other pigments. At the same time, energy storage efficiency in photosystem 2 for cyanobacteria containing Chl d and Chl f is not lower than that of cyanobacteria containing Chl a. Despite great interest in these unique chlorophylls, many questions related to functioning of such pigments in primary photosynthetic processes are still not elucidated. This review describes the latest advances in the field of Chl d and Chl f research and their role in primary photosynthetic processes of cyanobacteria.


Human ferritin H-chains can be obtained in non-assembled stable forms which have ferroxidase activity.
We found conditions to obtain the Leu-169-->Arg mutant of human ferritin H chain in a stable and non-assembled state. The protein obtained is an oligomer of subunits with a high degree of structured conformation, and when concentrated it re-assembles into ferritin cages. Functional studies showed that (i) it promotes iron oxidation like the assembled ferritin, but at slower rate, (ii) it is readily precipitated by the oxidised iron unless apotransferrin or L-chain ferritin are added to sequester Fe(III). The results confirm that ferroxidase activity is located within the H-chain, and indicate that the cages of the fully assembled ferritins are important not only in maintaining iron in a soluble form, but also in eliciting the activity of the ferroxidase centres.


Dexamethasone abolishes the activation by nerve growth factor of protein kinase N: effects of nerve growth factor and dexamethasone on protein kinase N.
Protein kinase N (PKN) is a basic 45-47 kDa serine/threonine protein kinase activated by NGF and several other factors in PC12 cells and other cell types. It is inhibited in vitro by purine analogs. In this work, we further characterize the modulation of PKN activity following exposure of PC12 cells to dexamethasone or NGF, which respectively direct these cells towards the chromaffin- or neuron-like phenotype. We show here that the two factors elicit opposite effects on the activation of the kinase: dexamethasone inhibits while NGF stimulates the basal level of PKN activity. Simultaneous addition to the cells of the factors causes no variation from basal kinase activity. Addition of dexamethasone not to the cells, but to partially purified PKN during the kinase assay, causes no modulation of the enzyme.


3D-planned corrective osteotomy of metacarpal arch disruption after Motec® wrist prosthesis.
We report two cases of metacarpal arch disruption after Motec® total wrist arthroplasty, with hyperextension of the third metacarpal and dorsal protrusion of the head. Correction osteotomies of the adjacent metacarpals using preoperative 3D surgical planning were successful. This report seeks to shed light on the origin of this deformation and to recommend some operative precautions. It is important that surgeons should be aware of the existence of this complication, as disruption of the transverse metacarpal arch affects both grasp and hand esthetics. LEVEL OF EVIDENCE: IV.


Methylphenidate modifies reward cue responses in adults with ADHD: An fMRI study.
Attention deficit hyperactivity disorder (ADHD) has been associated with neural hyposensitivity to reward-predicting cues. Methylphenidate is widely used in the management of the disorder's symptoms, but its effects on reward sensitivity in ADHD are unknown. The current study used fMRI to measure striatal responses to reward-predicting cues in adults with ADHD on and off methylphenidate and a control group, during a classical conditioning task. Responses to cued reward were also explored. Larger differences in the ventral striatum activation to reward cues versus non-reward cues were observed when the ADHD participants were on methylphenidate compared to placebo. In response to cued-reward outcome, an exploratory analysis showed methylphenidate reduced the BOLD time-series correlation between the dorsal striatum and dorsal medial prefrontal cortex. Methylphenidate's therapeutic effects may be mediated by altering reward processing in individuals with ADHD.


Costs of inpatient and emergency department care for chronic obstructive pulmonary disease in an elderly Medicare population.
Treatment in the hospital setting accounts for the largest portion of healthcare costs for COPD, but there is little information about components of hospital care that contribute most to these costs. The authors determined the costs and characteristics of COPD-related hospital-based healthcare in a Medicare population. Using administrative data from 602 hospitals, 2008 costs of COPD-related care among Medicare beneficiaries age ≥ 65 years were calculated for emergency department (ED) visits, simple inpatient admissions and complex admissions (categorized as intubation/no intensive care, intensive care/no intubation, and intensive care/intubation) in a cross-sectional study. Rates of death at discharge and trends in costs, length of stay and readmission rates from 2005 to 2008 also were examined. There were 45,421 eligible healthcare encounters in 2008. Mean costs were $679 (SD, $399) for ED visits (n = 10,322), $7,544 ($8,049) for simple inpatient admissions (n = 25,560), and $21,098 ($46,160) for complex admissions (n = 2,441). Intensive care/intubation admissions (n = 460) had the highest costs ($45,607, SD $94,794) and greatest length of stay (16.3 days, SD 13.7); intubation/no ICU admissions had the highest inpatient mortality (42.1%). In 2008, 15.4% of patients with a COPD-related ED visit had a repeat ED visit and 15.5-16.5% of those with a COPD-related admission had a readmission within 60 days. From 2005 to 2008, costs of admissions involving intubation increased 10.4-23.5%. Study limitations include the absence of objective clinical data, including spirometry and smoking history, to validate administrative data and permit identification of disease severity. In this Medicare population, COPD exacerbations and related inpatient and emergency department care represented a substantial cost burden. Admissions involving intubation were associated with the highest costs, lengths of stay and inpatient mortality. This population needs to be managed and treated adequately in order to prevent these severe events.


Comparison of the semisolid agar antifungal susceptibility test with the NCCLS M38-P broth microdilution test for screening of filamentous fungi.
Antifungal susceptibility testing of pathogenic molds is being developed. A simple screening semisolid agar antifungal susceptibility (SAAS) test accurately measures susceptibilities of yeasts. The performance of the SAAS screening test for filamentous fungi was assessed by comparing MICs of four antifungals (amphotericin B [AMB], AMB lipid complex [ABEL], itraconazole [ITZ], and posaconazole [POS]) for 54 clinical mold isolates with the results of the National Committee for Clinical Laboratory Standards (NCCLS) proposed broth microdilution method (M38-P). The SAAS test utilized inocula stabbed into tubes of 0.5% semisolid heart infusion agar. In both tests MICs were read after incubation at 35 degrees C for 48 h. The isolates tested were Aspergillus fumigatus, Aspergillus niger, Aspergillus flavus, other Aspergillus spp., Fusarium spp., Penicillium sp., Mucor sp., Scedosporium prolificans, Trichophyton sp., and an unidentified dematiaceous mold. Concordance of test results was determined as the percent agreement of MICs +/- 1 dilution. The overall agreement between the tests for each drug was as follows: AMB, 94%; ABEL, 83%; ITZ, 94%; POS, 94%. For the Aspergillus spp., all but one were susceptible to ITZ by SAAS test; all were susceptible to POS (MIC range, 0.25 to 4 micro g/ml). Three of six non-Aspergillus molds that were resistant to AMB and ABEL by SAAS (MIC >/= 2 micro g/ml) were also resistant by the NCCLS test. The SAAS test compared favorably to the NCCLS broth microdilution test for molds, and most of the clinical isolates tested were susceptible to all four drugs.


Tirzepatide 10 and 15 mg compared with semaglutide 2.4 mg for the treatment of obesity: An indirect treatment comparison.
To compare the efficacy of tirzepatide 10 and 15 mg with semaglutide 2.4 mg using an indirect treatment comparison. Using SURMOUNT-1 and STEP 1 trial data, mean percentage change in body weight from baseline and odds ratio (OR) of achieving 5% or greater weight loss were compared between tirzepatide 10 and 15 mg at week 72 and semaglutide 2.4 mg at week 68 using matching-adjusted indirect comparison of the efficacy estimand. Sensitivity analyses were completed using different methods, including the Bucher method, also using different estimands and/or time points. Greater reductions in percentage change in body weight were observed with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg (tirzepatide 10 mg mean difference: -4.67% [95% CI -5.91%, -3.43%]; tirzepatide 15 mg mean difference: -5.92% [95% CI -7.16%, -4.68%]; both P < .001). Similarly, more participants achieved 5% or greater weight loss with tirzepatide 10 mg (OR 2.61 [95% CI 1.48, 4.57]; P < .001) and 15 mg (OR 2.75 [95% CI 1.57, 4.81]; P < .001) compared with semaglutide 2.4 mg. All sensitivity analyses were consistent, except for an OR of achieving 5% or greater weight loss with tirzepatide 10 mg using the Bucher method to analyse the treatment regimen estimand (P = .074). Currently there are no direct comparisons of tirzepatide and semaglutide for weight management. Using the matching-adjusted indirect treatment comparison method to compare the efficacy of tirzepatide and semaglutide for chronic weight management, this analysis showed greater weight loss with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg.


Endoscopic transnasal dacryocystorhinostomy.
The rigid Hopkins endoscope has been applied to simplify the operation of dacryocystorhinostomy, preventing unnecessary trauma to the medial orbital tissues. The success of the surgical technique is absolutely dependent on a thorough knowledge of the relevant surgical anatomy.


Protocol to locally express cxcl12a during zebrafish olfactory organ development by combining IR-LEGO with live imaging.
Temporal and spatial regulation of gene expression is crucial for proper embryonic development. Infrared laser-evoked gene operator (IR-LEGO) can provide information for various developmental processes. Here, we present a protocol to locally express cxcl12a during zebrafish olfactory organ development1 using a combination of IR-LEGO and live imaging. We describe steps for implementing IR-LEGO, biological sample preparation, live imaging, data collection, and analysis. This protocol can be applied to virtually any genetically modified experimental organism.


Molecular characterization of Phytophthora palmivora responsible for bud rot disease of oil palm in Colombia.
Bud rot disease is a damaging disease of oil palm in Colombia. The pathogen responsible for this disease is a species of oomyctes, Phytophthora palmivora which is also the causal pathogen of several tropical crop diseases such as fruit rot and stem canker of cocoa, rubber, durian and jackfruit. No outbreaks of bud rot have been reported in oil palm in Malaysia or other Southeast Asian countries, despite this particular species being present in the region. Analysis of the genomic sequences of several genetic markers; the internal transcribe spacer regions (ITS) of the ribosomal RNA gene cluster, beta-tubulin gene, translation elongation factor 1 alpha gene (EF-1α), cytochrome c oxidase subunit I & II (COXI and COXII) gene cluster along with amplified fragment length polymorphism (AFLP) analyses have been carried out to investigate the genetic diversity and variation of P. palmivora isolates from around the world and from different hosts in comparison to Colombian oil palm isolates, as one of the steps in understanding why this species of oomycetes causes devastating damage to oil palm in Latin America but not in other regions. Phylogenetic analyses of these regions showed that the Colombian oil palm isolates were not separated from Malaysian isolates. AFLP analysis and a new marker PPHPAV, targeting an unclassified hypothetical protein, was found to be able to differentiate Malaysian and Colombian isolates and showed a clear clade separations. Despite this, pathogenicity studies did not show any significant differences in the level of aggressiveness of different isolates against oil palm in glasshouse tests.


Nonadherence to health promotion depending on chronic obstructive pulmonary disease severity.
Nonadherence to recommended health behaviors reportedly correlates with the prevalence and health outcomes of COPD, but the factors contributing to multiple health promotions are not well understood. To examine the factors associated with nonadherence to health behaviors, specifically focusing on COPD severity. We conducted a secondary data analysis with data from the 2016-2019 Korea National Health and Nutrition Examination Survey. The analyzed data were from 1,627 individuals aged over 40 years who had a FEV1/FVC ratio < 70% measured via spirometer. In this study, nonadherence to health behaviors is the sum of seven health-promoting behaviors in terms of smoking cessation, alcohol abstinence, regular exercise, weight control, recommended sleep time, influenza vaccination, and medical check-up. COPD patients' nonadherence to health behaviors was significantly associated with comorbidity (p=0.017), stress (p=0.002), and COPD severity (moderate, severe; p=0.010, p=0.039, respectively). In addition, the moderate and severe COPD groups showed a higher nonadherence rate than the mild COPD group. Specifically, nonadherence to weight control was the most significantly different behavior according to COPD severity levels, based on the GOLD classification of airflow limitation. Our study findings support that those with higher levels of stress, comorbidities, and severe disease conditions are less likely to adhere to health behaviors. Thus, healthcare providers and policymakers should provide tailored approaches according to COPD severity to educate and support appropriate health behaviors for individuals with COPD.


Cashew apple bagasse as new feedstock for the hydrogen production using dark fermentation process.
Cashew apple bagasse (CAB) has been studied as feedstock for the biohydrogen production using Clostridium roseum and the dark fermentation process. Pretreatment with alkaline hydrogen peroxide (CAB-AHP) on raw material and the acid and enzymatic hydrolysis have been taken into account to evaluate the H2 yields. Results show that the acid hydrolysate obtained from CAB produced higher H2 molar yield (HMY) (15 mmolH2/Lhydrolysate) than the acid hydrolysate from CAB-AHP (4.99 mmolH2/Lhydrolysate), These HMY were noticeably higher than values obtained from the enzymatic hydrolysate of CAB-AHP (1.05 mmolH2/Lhydrolysa) and the enzymatic hydrolysate of CAB (0.59 mmolH2/Lhydrolysa). The maximum biohydrogen productivity (12.57 mLH2/L.h) was achieved using the acid hydrolysate from CAB, with a H2 content of about 72% vol, that could be satisfactory in view of an energetic applications of the biogas. Results suggest that CAB could be considered for the hydrogen production process, providing an appropriate destination for this lignocellulosic biomass, and consequently, reducing the environmental impact it can exert.


Application of an integrated catchment-lake model approach for simulating effects of climate change on lake inputs and biogeochemistry.
Climate change is simultaneously affecting lakes and their catchments, resulting in altered runoff patterns in the catchment and modified mixing and biogeochemical dynamics in lakes. The effects of climate change in a catchment will eventually have an impact on the dynamics of a downstream water body as well. An integrated model would allow considering how changes in the watershed affect the lake, but coupled modelling studies are rare. In this study we integrate a catchment model (SWAT+) and a lake model (GOTM-WET) to obtain holistic predictions for Lake Erken, Sweden. Using five different global climate models, projections of climate, catchment loads and lake water quality for the mid and end of the 21st century have been obtained under two future scenarios (SSP 2-45 and SSP 5-85). Temperature, precipitation and evapotranspiration will increase in the future, overall resulting in an increase in water inflow to the lake. An increasing importance of surface runoff will also have consequences on the catchment soil, hydrologic flow paths, and the input of nutrients to the lake. In the lake, water temperatures will rise, leading to increased stratification and a drop in oxygen levels. Nitrate levels are predicted to remain unchanged, while phosphate and ammonium levels increase. A coupled catchment-lake configuration such as that illustrated here allows prediction of future biogeochemical conditions of a lake, including linking land use changes to changing lake conditions, as well as eutrophication and browning studies. Since climate affects both the lake and the catchment, simulations of climate change should ideally take into account both systems.


Iatrogenic injury to the phrenic nerve nerve in infants and young children.
Five cases of iatrogenic phrenic nerve injury in infants are presented. The difficulties of diagnosis and treatment are outlined and reference made to the possible sites of injury. The necessity for early recognition of the injury, and its prompt relief if indicated, are stressed.


Oral BG-12 (dimethyl fumarate) for relapsing-remitting multiple sclerosis: a review of DEFINE and CONFIRM. Evaluation of: Gold R, Kappos L, Arnold D, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med 2012;367:1098-107; and Fox RJ, Miller DH, Phillips JT, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 2012;367:1087-97.
Multiple sclerosis (MS) is an autoimmune neurodegenerative disease of the central nervous system involving inflammation, chronic demyelination and axonal loss. MS affects more than 2 million people worldwide. This article aims to summarize the findings from two pivotal 2-year, randomized, double-blind, placebo-controlled, Phase III studies of BG-12 (dimethyl fumarate) for relapsing-remitting MS (RRMS): DEFINE (Determination of the Efficacy and Safety of Oral Fumarate in RRMS) and CONFIRM (Comparator and an Oral Fumarate in RRMS). Results from both studies demonstrated that BG-12 provides clinical and radiological efficacy over 2 years across a range of outcomes. These results were apparent as early as 12 weeks and sustained over the course of both studies. BG-12 was found to have an acceptable safety profile, with a similar overall incidence of adverse events across all treatment groups. The combination of robust efficacy, ease of administration and established safety profile is unique to a new therapy in MS. Findings from the pivotal Phase III studies support BG-12 as a potential initial oral treatment for patients with RRMS or as an alternative to other currently available therapies.


Deciphering the biodesulfurization pathway employing marine mangrove Bacillus aryabhattai strain NM1-A2 according to whole genome sequencing and transcriptome analyses.
In the biogeochemical cycle, sulfur oxidation plays a vital role and is typically referred to as the elemental sulfur or reductive sulfide oxidation process. This study aimed to characterize a subtropical mangrove-isolated bacterial strain using biochemical, whole-genome, and transcriptome sequencing analyses to enhance our understanding of sulfur metabolism and biodegradation from a molecular genetic perspective. Strain NM1-A2 was characterized as Gram-positive and found to have a close molecular phylogenetic relationship with Bacillus aryabhattai. NM1-A2 efficiently converted dibenzothiophene (DBT) into 2-hydroxybiphenyl (2-HBP) via a 4S pathway with 95% efficiency, using enzymes encoded by the dsz operon (dszA, dszB, and dszC), which determine monooxygenases (DszA & DszC) and desulfinase (DszB). The whole-genome sequence of NM1-A2 had a length of approximately 5,257,678 bp and included 16 sulfur metabolism-related genes, featuring the ABC transport system, small subunit (ssu) and cysteine (cys) gene families, and adenosine 5'-phosphosulfate (APS) and 3'-phosphoadenosine-5'-phosphosulfate (PAPS) biosynthesis-related genes. Transcriptomic analysis of NM1-A2 using three sulfur groups-magnesium sulfate (MS), sulfur powder (SP), and sodium thiosulfate (ST) resulted in a significant number of differentially expressed genes (1200, 2304, and 2001, respectively). This analysis revealed that intracellular cysteine concentration directly regulated the expression of cys and ssu genes. Sulfate did not directly affect cys gene expression but repressed ssu gene expression. The cys gene expression levels decreased during the conversion of sulfate to sulfide and cysteine. The transcriptomic data was validated by analyzing the expression patterns of NM1-A2 using real-time quantitative PCR validation analysis. The expression levels of cysl, mccB, and nrnA were significantly upregulated, while cysH, metB, and sat were downregulated in the SP, ST, and MS groups, respectively. This research contributes to our understanding of marine mangrove microorganisms' bacterial efficiency through characterization, whole-genome, and transcriptome sequencing-based molecular degradation of organic compounds in the mangrove ecosystem, which may enhance nutrient availability.


Elevated CO2 aggravates invasive thrip damage by altering its host plant nutrient and secondary metabolism.
As atmospheric CO2 concentration continues to increase, plants using CO2 as raw materials for photosynthesis will inevitably be affected, which in turn affects the life history and behavior of herbivorous insects. Our previous research has shown increased food intake and aggravated damage of western flower thrips, Frankliniella occidentalis to kidney bean (Phaseolus vulgaris) caused by elevated CO2 (eCO2), however the molecular mechanism of this phenomenon is unclear. In this study, the comparative transcriptome analysis combined with corresponding phenotypic changes were studied to reveal the molecular mechanism of interaction between F. occidentalis and P. vulgaris under eCO2. Inferred from the results, eCO2 had different degrees of inhibition to the defense responses caused by thrips infestation in P. vulgaris leaf sap based on nutrients, plant hormones and secondary metabolites, making P. vulgaris leaves less resistant to thrips under eCO2 compared to ambient CO2 (aCO2). Besides, the contents of glucose, trehalose, triglycerides and free fatty acids in F. occidentalis adults increased significantly after feeding on the P. vulgaris leaf sap with significantly increased soluble sugars content under eCO2, which might lead to glucolipid metabolic disorders and increased food intake of F. occidentalis adults. The results indicated that decreased plant defense of P. vulgaris and increased food intake of F. occidentalis adults were combined to aggravate the thrips damage under eCO2, providing a theoretical basis for future occurrence trend of thrips under eCO2.


Prognostic impact of pre- and postoperative tumor markers in patients with intrahepatic cholangiocarcinoma.
The present study assessed the impact of pre- and postoperative tumor markers on the survival of patients with intrahepatic cholangiocarcinoma. Medical records of 73 patients with intrahepatic cholangiocarcinoma were reviewed retrospectively. The pre- and postoperative carcinoembryonic antigen and carbohydrate antigen 19-9 levels were assessed. Patient characteristics, clinicopathological factors, and prognostic factors were analyzed. The median recurrence-free survival and overall survival were 30.0 and 90.9 months, respectively. A multivariate survival analysis revealed that elevated postoperative carbohydrate antigen 19-9 (p = 0.023) was the only independent poor prognostic factor. The median overall survival of patients with normal and elevated postoperative carbohydrate antigen 19-9 levels was 101.4 and 15.7 months (p < 0.001), respectively. Multivariate logistic regression identified elevated preoperative carbohydrate antigen 19-9 as an independent preoperative risk factor for elevated postoperative carbohydrate antigen 19-9. The optimal cutoff value of preoperative carbohydrate antigen 19-9 for predicting elevated postoperative carbohydrate antigen 19-9 was 40 U/mL, with a sensitivity and specificity of 92% and 87%, respectively (area under curve = 0.915). Elevated postoperative carbohydrate antigen 19-9 was an independent poor prognostic factor. Preoperative predictors, such as elevated preoperative carbohydrate antigen 19-9, may indicate the need for neoadjuvant therapies to improve the survival.


A novel role of pirfenidone in attenuation acetic acid induced ulcerative colitis by modulation of TGF-β1 / JNK1 pathway.
Colon diseases are a major health burden, particularly ulcerative colitis, in both men and women worldwide. Environmental and genetic factors in various colonic pathologies influence the onset and outcome of diseases. As the evidence from recent research is considered, the importance of inflammation in the onset, progression, and outcome is gaining more traction. The goal of this study was to see if pirfenidone could treat ulcerative colitis (UC) and if so, what mechanisms were involved. By intracolonic instillation [2 ml, 3 percent v/v acetic acid (AA)], ulcerative colitis was induced. Pirfenidone was administered to rats in different experimental groups (125 or 250 and 500 mg/kg, orally) for two weeks. Compared to normal group, the AA group showed an increase in colon weight, length, body weight, clinical evaluation, and macroscopic scoring of UC, serum lactate dehydrogenase, C-reactive protein, malondialdehyde, while decreasing serum total antioxidant capacity. Significant increases in colon Jun N terminal kinase1 (JNK1), transforming growth factor-beta (TGF-β1), interleukin 1 beta (IL1β), and Caspase-3 content. Furthermore, immunohistochemical staining revealed increased nuclear factor kappa B (NF-κB) expression along with histopathological changes. Pirfenidone inhibited inflammatory biomarkers release and restored oxidants/antioxidants hemostasis. In a dose-dependent manner, pirfenidone treatment showed a significantly decrease in all of these parameters. In addition, pirfenidone has significantly preserved the histopathological architecture of tissues. Current data demonstrate that Pirfenidone protects against AA-induced UC by modulating the TGF-β1/JNK1 and Caspase-3 pathways. Pirfenidone's antioxidant, anti-inflammatory, and anti-apoptotic properties are thought to be responsible for its therapeutic benefit.


THE Hb S/beta+ -thalassemia phenotype demonstrates that the IVS-I (-2) (A>C) mutation is a mild beta-thalassemia allele.
We report a family in which two siblings are compound heterozygotes for Hb S [beta6(A3)GluVal] and a rare beta-globin mutation [IVS-I (-2) (A>C)]. Both patients had significant levels of Hb A, indicating that the IVS-I (-2) mutation is a relatively mild beta(+)-thalassemia (beta(+)-thal) allele. This mutation, in compound heterozygosity with Hb S, does not necessarily lead to a mild clinical course.


Synthesis and antitumor activity of novel 6-aryl and 6-alkylpyrazolo[3,4-d]pyrimidin-4-one derivatives.
A series of new 6-arylpyrazolo[3,4-d]pyrimidin-4-ones and 6-alkylpyrazolo[3,4-d]pyrimidin-4-ones were synthesized. Some of the newly synthesized compounds were tested in vitro on human colon tumor cell line (HCT116). Most of the test compounds exploited potent antitumor activity, especially compound 10a which displayed the highest activity among the test compounds with IC(50) equal to 0.47 μg/mL.


[The thermophilic streptomycetes flora in milk powders and condensed milk products (author's transl)].
247 specimens of powdered milk and 165 of condensed milk were tested for their contamination with thermophile Streptomycetes. Colonies of these contaminants were isolated from all specimens of powdered milk and from 73 samples of condensed sweeted milk. The isolated strains corresponded with the following species of thermophilic Streptomycetes: Thermoactinomyces vulgaris, Tsiklinsky 1899, Thermoactinomyces vulgaris, Tsiklinsky 1899 "giant colonies", Micromonospora sp. (Agre et al., 1).


Reversal of boswellic acid analog BA145 induced caspase dependent apoptosis by PI3K inhibitor LY294002 and MEK inhibitor PD98059.
PI3K/Akt and ERK pathways are important for growth and proliferation of many types of cancers. Therefore, PI3K inhibitor LY294002 (LY) and MEK1/2 inhibitor PD98059 (PD) are used to sensitize many types of cancer cell lines to chemotherapeutic agents, where AKT and ERK pathways are over activated. However, in this study, we show for the first time that PD could protect the leukemia cells independent of ERK pathway inhibition, besides, we also report a detailed mechanism for antiapoptotic effect of LY in HL-60 cells against the cytotoxicity induced by a boswellic acid analog BA145. Apoptosis induced by BA145 is accompanied by downregulation of PI3K/Akt and ERK pathways in human myelogenous leukemia HL-60 cells, having activating N-Ras mutation. Both LY and PD protected the cells against mitochondrial stress caused by BA145, and reduced the release of cytochrome c and consequent activation of caspase-9. LY and PD also diminished the activation of caspase-8 without affecting the death receptors. Besides, LY and PD also reversed the caspase dependent DNA damage induced by BA145. Further studies revealed that LY and PD significantly reversed the inhibitory effect of BA145 on cell cycle regulatory proteins by upregulating hyperphosphorylated retinoblastoma, pRB (S795) and downregulating p21 and cyclin E. More importantly, all these events were reversed by caspase inhibition by Z-VAD-fmk, suggesting that both LY and PD act at the level of caspases to diminish the apoptosis induced by BA145. These results indicate that inhibitors of PI3K/Akt and ERK pathways can play dual role and act against chemotherapeutic agents.


Noninvasive Ventilation for the Emergency Physician.
Noninvasive ventilation (NIV) improves oxygenation and ventilation, prevents endotracheal intubation, and decreases the mortality rate in select patients with acute respiratory failure. Although NIV is used commonly for acute exacerbations of chronic obstructive pulmonary disease and acute cardiogenic pulmonary edema, there are emerging indications for its use in the emergency department. Emergency physicians must be knowledgeable regarding the indications and contraindications for NIV in emergency department patients with acute respiratory failure as well as the means of initiating it and monitoring patients who are receiving it.


Investigations on the Novel Antimalarial Ferroquine in Biomimetic Solutions Using Deep UV Resonance Raman Spectroscopy and Density Functional Theory.
Deep ultraviolet (DUV) resonance Raman experiments are performed, investigating the novel, promising antimalarial ferroquine (FQ). Two buffered aqueous solutions with pH values of 5.13 and 7.00 are used, simulating the acidic and neutral conditions inside a parasite's digestive vacuole and cytosol, respectively. To imitate the different polarities of the membranes and interior, the buffer's 1,4-dioxane content was increased. These experimental conditions should mimic the transport of the drug inside malaria-infected erythrocytes through parasitophorous membranes. Supporting density functional theory (DFT) calculations on the drug's micro-speciation were performed, which could be nicely assigned to shifts in the peak positions of resonantly enhanced high-wavenumber Raman signals at λexc = 257 nm. FQ is fully protonated in polar mixtures like the host interior and the parasite's cytoplasm or digestive vacuole (DV) and is only present as a free base in nonpolar ones, such as the host's and parasitophorous membranes. Additionally, the limit of detection (LoD) of FQ at vacuolic pH values was determined using DUV excitation wavelengths at 244 and 257 nm. By applying the resonant laser line at λexc = 257 nm, a minimal FQ concentration of 3.1 μM was detected, whereas the pre-resonant excitation wavelength 244 nm provides an LoD of 6.9 μM. These values were all up to one order of magnitude lower than the concentration found for the food vacuole of a parasitized erythrocyte.


Supporting nursing and allied health student placements in rural and remote Australia: a narrative review of publications by university departments of rural health.
University departments of rural health are Commonwealth-funded to improve recruitment and retention of the rural allied health and nursing (including midwifery) workforce, primarily through student placements. We examined publications by university departments of rural health that were focused on allied health and nursing students undertaking placements in rural Australia, to understand the characteristics, main findings and implications of the research conducted. Interprofessional learning was a key feature of placements and placement education, although other activities such as community engagement added to placement experiences. Factors such as quality supervision and being involved in the community contributed to a positive placement experience and increased rural practice intention. Tracking studies showed a relationship between rural placements, rural practice intention and rural practice. Rural placements occurred across a variety of settings and in locations consistent with the policy framework. Embedding university departments of rural health in rural communities enabled staff to build relationships and increase placement capacity.


Susceptibility to COVID-19 Diagnosis in People with Down Syndrome Compared to the General Population: Matched-Cohort Study Using Primary Care Electronic Records in the UK.
During the COVID-19 pandemic, people with Down syndrome (DS) have experienced a more severe disease course and higher mortality rates than the general population. It is not yet known whether people with DS are more susceptible to being diagnosed with COVID-19. To explore whether DS is associated with increased susceptibility to COVID-19. Matched-cohort study design using anonymised primary care electronic health records from the May 2021 release of Clinical Practice Research Datalink (CPRD) Aurum. Electronic health records from approximately 1400 general practices (GPs) in England. 8854 people with DS and 34,724 controls matched for age, gender and GP who were registered on or after the 29th January 2020. The primary outcome was COVID-19 diagnosis between January 2020 and May 2021. Conditional logistic regression models were fitted to estimate associations between DS and COVID-19 diagnosis, adjusting for comorbidities. Compared to controls, people with DS were more likely to be diagnosed with COVID-19 (7.4% vs 5.6%, p ≤ 0.001, odds ratio (OR) = 1.35; 95% CI = 1.23-1.48). There was a significant interaction between people with DS and a chronic respiratory disease diagnosis excluding asthma and increased odds of a COVID-19 diagnosis (OR = 1.71; 95% CI = 1.20-2.43), whilst adjusting for a number of comorbidities. Individuals with DS are at increased risk for contracting COVID-19. Those with underlying lung conditions are particularly vulnerable during viral pandemics and should be prioritised for vaccinations.