Health-related quality of life in children with chronic myeloid leukemia in the chronic phase.
This study aimed to explore the health-related quality of life (HRQoL) and associated variables in children with chronic myeloid leukemia in the chronic phase (CML-CP) receiving tyrosine kinase inhibitors (TKIs). A cross-sectional questionnaire was given to children with CML and their parents, who were < 18 years at diagnosis of CML and < 19 years at study. The questionnaire comprised three parts, including demographic information, clinical information, and the Chinese version of Pediatric Quality of Life Inventory™ (PedsQL™) Cancer Module 3.0 as HRQoL questionnaire. A total of 240 respondents data were analyzed. Multivariate analysis showed that children with symptoms had worse pain (- 10.2; P < 0.001), nausea (- 17.3; P = 0.001), more treatment anxiety (- 7.2; P = 0.005), worse self-assessment appearance (- 7.1; P = 0.001), communication problems (- 6.4; P = 0.001), and worse HRQoL (- 7.0; P < 0.001). Children with mothers having low educational qualifications had worse pain (- 6.0; P = 0.014), more worried about future (- 5.4; P = 0.042), worse cognition problems (- 7.1; P = 0.002), worse communication problems (- 5.5; P = 0.008), and worse HRQoL (- 4.3; P = 0.005). Younger age children at study had more procedural anxiety (2.7; P = 0.001), treatment anxiety (- 1.7; P = 0.014) and cognition problem (3.6; P < 0.001), as well as worse HRQoL (1.8; P = 0.008). However, older age children at diagnosis were more worried about future (- 2.8; P = 0.001), worse self-assessment appearance (- 1.1; P = 0.042) and worse HRQoL (- 1.8; P = 0.007). Other variables significantly associated with worse HRQoL included female gender, rural household registration and their father's low education level. Parents reported more gastrointestinal disorders, were worried about the future and had less concern about appearance than their children. Female gender, older age at diagnosis, younger age at study, lower mother's education level, and TKI-related symptoms are significantly associated with worse HRQoL in Children with CML. Children and their parents have different priorities in the HRQoL.


MIL-101 (Cr) @ graphene oxide-reinforced hollow fiber solid-phase microextraction coupled with high-performance liquid chromatography to determine diazinon and chlorpyrifos in tomato, cucumber and agricultural water.
An effective, sensitive, relatively-fast and cost-effective method was developed to determine two types of selected organophosphorus pesticides (OPPs) including diazinon and chlorpyrifos in tomato, cucumber and agricultural water samples through applying MIL-101@ graphene oxide-reinforced hollow fiber solid-phase microextraction (MIL-101@GO-HF-SPME). The extracted analytes were desorbed via organic solvent and analyzed through high-performance liquid chromatography-ultraviolet detection (HPLC-UV) after extraction. MIL-101@ GO sorbent which was previously prepared and characterized was first dispersed in methanol by ultrasonication and then immobilized into the pores of a hollow fiber (HF). Several factors involved in MIL-101@GO-HF-SPME experiment such as desorption volume, ionic strength, desorption time, sample pH, extraction time and stirring rate were screened via Plackett-Burman design and then optimized through Box-Behnken design with the purpose of reaching the highest extraction efficiency. The above method showed a good linear range (1-500 μg L-1) with coefficient of determination higher than 0.9948, low limits of determination (LODs, 0.21 and 0.27 μg L-1), acceptable limits of quantifications (LOQs, 0.72 and 0.91 μg L-1), good enrichment factors (EFs, 49 and 41), acceptable absolute recoveries (AR%, 49 and 41%) and good spiking recoveries (88-104%) under the optimized condition at three different spiked levels for chlorpyrifos and diazinon, respectively. It is worth mentioning that due to the clean-up function of HF, there is no time-consuming sample pretreatment procedure (e.g. filtration or centrifugation) prior to the microextraction. Therefore, the presented method took advantage of both excellent adsorption performance of MIL-101@GO and the clean-up function of HF. The results confirmed that the presented method would be promising for the analysis of various types of these pesticides in environmental and vegetable samples.


Added Value of the Vascular Index on Superb Microvascular Imaging for the Evaluation of Breast Masses: Comparison With Grayscale Ultrasound.
To evaluate the value of the vascular index (VI) on Superb Microvascular Imaging (SMI; Canon Medical Systems Corporation, Tokyo, Japan) in comparison with grayscale ultrasound (US) alone for assessing breast masses. We evaluated a total of 70 breast masses (36 malignant and 34 benign lesions) in 70 consecutive patients using grayscale US and SMI. Two breast radiologists analyzed grayscale US alone and the combination of grayscale US and SMI. They also measured the VI based on SMI. The diagnostic performance of grayscale US alone and the combination of grayscale US and SMI was compared. The VI was compared between benign and malignant masses, and the optimal cutoff value was determined. In addition, the interobserver agreement in imaging analyses and the VI was assessed. The interobserver agreements in imaging analyses and the VI were almost perfect. The VI of malignant breast masses was significantly higher than that of benign lesions (P < .001). The optimal cutoff value of the VI for differentiating between malignant and benign breast masses was 2.95, with sensitivity of 86.1% and specificity of 91.2%. The diagnostic performance values of grayscale US alone and the combination of grayscale US and SMI were 0.824 and 0.912, respectively, for reader 1 (P = .028) and 0.795 and 0.853 for reader 2 (P = .101). The VI on SMI was significantly higher for malignant breast masses than for benign lesions, with high interobserver agreement. Our study suggests that the combination of grayscale US and SMI with the VI could improve the characterization of breast masses.


Proteomic analysis of vitreous from diabetic macular edema.
To identify and analyze diabetic macular edema (DME)-related proteins in the vitreous, en masse, using two-dimensional gel (2D gel) electrophoresis and mass-spectrometry (MS). Vitreous samples were corrected from 20 eyes with pre-proliferative diabetic retinopathy associated with DME (DME group) and without DME (non-DME group). They were subjected to 2D gel electrophoresis, and the spot intensities were compared between the groups. Apparently visible spots were excised from the gel, and the proteins were identified by liquid chromatography tandem MS (LC MS/MS) sequence analysis. We identified 14 proteins from the DME group, and 15 proteins from the non-DME group. The intensity of eight spots was markedly higher in DME than non-DME samples and one spot was detected only in non-DME samples. From the eight spots, six proteins were identified, including PEDF, ApoA-4, ApoA-1, Trip-11, PRBP, and VDBP. On the other hand, Apo H was expressed only in non-DME. Certain vitreous proteins expressed exclusively in DME and lacked in DME. These chemical mediators in the posterior vitreous may play a role in the pathogenesis of DME.


Enhancer analysis of the Drosophila zinc finger transcription factor Earmuff by gene targeting.
Many transcription factors are involved in the formation of the brain during the development of Drosophila melanogaster. The transcription factor Earmuff (Erm), a member of the forebrain embryonic zinc finger family (Fezf), is one of these important factors for brain development. One major function of Earmuff is the regulation of proliferation within type II neuroblast lineages in the brain; here, Earmuff is expressed in intermediate neural progenitor cells (INPs) and balances neuronal differentiation versus stem cell maintenance. Erm expression during development is regulated by several enhancers. In this work we show a functional analysis of erm and some of its enhancers. We generated a new erm mutant allele by gene targeting and reintegrated Gal4 to make an erm enhancer trap strain that could also be used on an erm mutant background. The deletion of three of the previously analysed enhancers showing the most prominent expression patterns of erm by gene targeting resulted in specific temporal and spatial defects in defined brain structures. These defects were already known but here could be assigned to specific enhancer regions. This analysis is to our knowledge the first systematic analysis of several large enhancer deletions of a Drosophila gene by gene targeting and will enable deeper analysis of erm enhancer functions in the future.


[Viruses, virus-like and virus-related structures in nasopharyngeal carcinoma (author's transl)].
Five cases of nasopharyngeal carcinoma with typically elevated EB-virus-antigen-titer were studied by light- and electron microscopic methods. Within the cytoplasm corona viruses in different forms, regular capsid-like particles with a diameter of 60 nm, tubuloreticular aggregates, and pathologic alterations of the membranes of the endoplasmatic reticulum could be found. The nuclei of the tumour cells often showed particles within the nucleoplasm with an average diameter of 100 nm containing a central core; the appearance of the particles is similar to that of herpes viruses as shown in the literature concerning EB-viruses. Atypic mitoses are common as well as free nucleoplasma-like condensates within the ground cytoplasm. Multiple doubling of the membranes of the endoplasmatic reticulum are characteristic for the tumor cell cytoplasm. Myelin figures are often situated within the enlarged tubules of the E. R., within mitochondria and within the nuclei. The results are discussed concerning the possible viral etiology of nasopharyngeal carcinoma. We do not believe that the particles found within the nucleoplasm have a relation to nuclear pores. The arguments are discussed.


Influence of concentration on the kinetics of SC-infused insulin. Comparison between square-wave SC infusion and bolus SC injection.
The influence of various concentrations of a constantly SC-infused insulin solution on plasma free insulin (PFI) levels wa studied in eight type 1 diabetic subjects. Soluble insulin at three different concentrations (10, 40, and 100 U/mL) was pumped at two different rates: 1.5 U/h between meals and 15 U/h for 30 minutes just before meals. For each randomly allocated concentration, PFI levels were studied twice in the same day during two six hour postmeal periods. In addition, at the end of the U40 infusion, a comparable amount of insulin was injected as a bolus. The total amount (56 U/d) and distribution of insulin delivered were similar in all patients and with each concentration. The mean maximum PFI levels were 39 +/- 7.2, 28.4 +/- 3.4, 36.2 +/- 6.4, and 29.2 +/- 7.6 mus U/mL, respectively, during the U10, U40, and U100 infusions and the U40 bolus injection; these values were observed, respectively, 60, 120, 90, and 90 minutes after a step up increase of insulin infusion and after the SC bolus injection. PFI levels returned to basal values between three and five hours after the step decrease. There was no significant difference in the kinetics of PFI levels variation, whatever the concentration in the range of 10 to 100 U/mL. For U40 these kinetics did not differ from that observed after a bolus SC injection of soluble insulin.


Mechanical characterisation of porcine rectus sheath under uniaxial and biaxial tension.
Incisional hernia development is a significant complication after laparoscopic abdominal surgery. Intra-abdominal pressure (IAP) is known to initiate the extrusion of intestines through the abdominal wall, but there is limited data on the mechanics of IAP generation and the structural properties of rectus sheath. This paper presents an explanation of the mechanics of IAP development, a study of the uniaxial and biaxial tensile properties of porcine rectus sheath, and a simple computational investigation of the tissue. Analysis using Laplace׳s law showed a circumferential stress in the abdominal wall of approx. 1.1MPa due to an IAP of 11kPa, commonly seen during coughing. Uniaxial and biaxial tensile tests were conducted on samples of porcine rectus sheath to characterise the stress-stretch responses of the tissue. Under uniaxial tension, fibre direction samples failed on average at a stress of 4.5MPa at a stretch of 1.07 while cross-fibre samples failed at a stress of 1.6MPa under a stretch of 1.29. Under equi-biaxial tension, failure occurred at 1.6MPa with the fibre direction stretching to only 1.02 while the cross-fibre direction stretched to 1.13. Uniaxial and biaxial stress-stretch plots are presented allowing detailed modelling of the tissue either in silico or in a surrogate material. An FeBio computational model of the tissue is presented using a combination of an Ogden and an exponential power law model to represent the matrix and fibres respectively. The structural properties of porcine rectus sheath have been characterised and add to the small set of human data in the literature with which it may be possible to develop methods to reduce the incidence of incisional hernia development.


Biological studies of Chlorella pyrenoidosa (strain LARG-1) cultures grown under space flight conditions.
This paper reports data from an electron microscopic analysis of Chlorella pyrenoidosa (LARG-1) cultures after five days of growth in the dark on a semiliquid mineral/glucose medium in the IFS-2 device on board the Soyuz 27-Salyut 6-Soyuz 28 orbital research complex (Soviet-Czechoslovak experiment "Chlorella-1"). For space flight of five days duration the ultrastructural cellular organization of the flight and control cultures were similar. This testifies to normal cell function.


The antidepressant-like effects of topiramate alone or combined with 17β-estradiol in ovariectomized Wistar rats submitted to the forced swimming test.
There is a significant delay in the clinical response of antidepressant drugs, and antidepressant treatments produce side effects. We examined the relationship between 17β-estradiol and topiramate in ovariectomized Wistar rats submitted to the forced swimming test (FST). Topiramate was administered alone or combined with 17β-estradiol to ovariectomized rats submitted to the FST. Topiramate (20 mg/kg, P < 0.05; 30 mg/kg, P < 0.05) reduced immobility by increasing swimming; these effects were antagonized by finasteride (50 mg/kg). In interaction experiments, topiramate (10 mg/kg) plus 17β-estradiol (5 micrograms per rat; P < 0.05) reduced immobility by increasing swimming behavior. Besides, 17β-estradiol (2.5 micrograms per rat) shortened the onset of the antidepressant-like effects of topiramate (P < 0.05). In the open field test, topiramate alone or combined with 17β-estradiol (P < 0.05) reduced locomotion. Topiramate alone or combined with 17β-estradiol produced antidepressant-like actions; and 17β-estradiol shortened the onset of the antidepressant-like effects of topiramate.


Differential effects of testosterone on neuronal populations and their connections in a sensorimotor brain nucleus controlling song production in songbirds: a manganese enhanced-magnetic resonance imaging study.
Nucleus HVC (formerly called high vocal center) of songbirds contains two types of projecting neurons connecting HVC respectively to the nucleus robustus archistriatalis, RA, or to area X. These two neuron classes exhibit multiple neurochemical differences and are differentially replaced by new neurons during adult life: high rates of neuronal replacement are observed in RA-projecting neurons only. The activity of these two types of neurons may also be modulated differentially by steroids. We analyzed by magnetic resonance imaging the effect of testosterone on the volume of RA and area X and on the dynamics of Mn(2+) accumulation in RA and area X of female starlings that had been injected with MnCl(2) through a permanent cannula implanted in HVC. Repeated visualization 6 weeks apart (before and after testosterone treatment) identified a volume increase of both nuclei in testosterone-treated birds associated with a concomitant decrease in controls. Following testosterone treatment, the total amount of Mn(2+) transported to RA and area X increased but the dynamics of accumulation, reflecting in part the activity of HVC neurons, was specifically altered in area X but not in RA. These data indicate that testosterone differentially affects the RA- and area X-projecting neurons in HVC. Manganese-enhanced magnetic resonance imaging (ME-MRI) thus provides repeated measures of connected brain areas and demonstrates testosterone-dependent regionally specific changes in brain activity and functional connectivity. The slow time scales investigated by this technique (compared to functional MRI) appear ideally suited for characterizing slow processes such as those involved in brain plasticity and learning.


Influence of benzodiazepines on the response of the guinea-pig isolated trachea to the contractile action of adenosine.
The effects of diazepam and other agonists of central or peripheral benzodiazepine receptors were studied on the contractile action of adenosine, 2-chloroadenosine and R-PIA (N6-(L-2-phenylisopropyl)-adenosine) on the guinea-pig isolated trachea. These effects were compared to those of dipyridamole. Diazepam 10(-7) to 10(-5) M potentiated the efficacy of adenosine; the maximal contractile effect of adenosine (% vs. acetylcholine 10(-3) M) was 20.4 +/- 4.2 (n = 21) in control conditions and 45.5 +/- 3.7 (n = 6; P less than 0.001) in the presence of diazepam 10(-5) M. Ro5-4864 (10(-7) to 10(-5) M) or alpidem (10(-7) to 10(-5) M), both agonists of peripheral benzodiazepine receptors, potentiated the contractile effects of adenosine to the same extent as diazepam. Clonazepam and zopiclone, both agonists of central benzodiazepine receptors, did not modify these effects. Antagonists of central (flumazenil) or peripheral (RP 52028) benzodiazepine receptors had no influence on the interaction between diazepam or Ro5-4864 and adenosine. Conversely, dipyridamole significantly reduced (10(-7) M) or suppressed (10(-6) M) the contractile effects of adenosine. The contractile effects of 2-chloroadenosine and R-PIA were weakly affected in presence of high concentrations of diazepam and dipyridamole. Epithelium removal potentiated the contractile effect of adenosine on the guinea-pig isolated trachea and increased the potentiating effect of diazepam. It is concluded that benzodiazepines and related compounds can potentiate the contractile effect of adenosine on the guinea-pig isolated trachea through the activation of a peripheral receptor for the benzodiazepines and the resulting inhibition of adenosine uptake.


Co-activation patterns across multiple tasks reveal robust anti-correlated functional networks.
Whether antagonistic brain states constitute a fundamental principle of human brain organization has been debated over the past decade. Some argue that intrinsically anti-correlated brain networks in resting-state functional connectivity are an artifact of preprocessing. Others argue that anti-correlations are biologically meaningful predictors of how the brain will respond to different stimuli. Here, we investigated the co-activation patterns across the whole brain in various tasks and test whether brain regions demonstrate anti-correlated activity similar to those observed at rest. We examined brain activity in 47 task contrasts from the Human Connectome Project (N = 680) and found robust antagonistic interactions between networks. Regions of the default network exhibited the highest degree of cortex-wide negative connectivity. The negative co-activation patterns across tasks showed good correspondence to that derived from resting-state data processed with global signal regression (GSR). Interestingly, GSR-processed resting-state data was a significantly better predictor of task-induced modulation than data processed without GSR. Finally, in a cohort of 25 patients with depression, we found that task-based anti-correlations between the dorsolateral prefrontal cortex (DLPFC) and subgenual anterior cingulate cortex were associated with clinical efficacy of transcranial magnetic stimulation therapy targeting the DLPFC. Overall, our findings indicate that anti-correlations are a biologically meaningful phenomenon and may reflect an important principle of functional brain organization.


Personal pronouns and the autistic child.
The long-recognized difficulties of the speaking autistic child with the use and nonuse of personal pronouns ["reversals" and "avoidance"] have been generally attributed either to the nondifferentiation of the self or to the frequently coexisting symptom of echolalia. These explanations are reconsidered in this eclectic analysis from the perspective of current theory and research in development of self and of language. Emphasis is on studies of normal development of personal pronouns and the roles played in that process by listening, echoic memory, mitigated echolalia [recoding], and person deixis. It is concluded that multiple developmental obstacles of a social, cognitive, and grammatical nature underlie the more obvious symptoms and militate against the child's resolution of labels and their referents. Treatment alternatives that de-emphasize the primacy of I are offered.


An Electronic Search Algorithm for Early Disseminated Intravascular Coagulopathy Diagnosis in the Intensive Care Unit: A Derivation and Validation Study.
We aim to create and validate an electronic search algorithm for accurate detection of disseminated intravascular coagulopathy (DIC) from medical records. Patients with DIC in Mayo Clinic's intensive care units (ICUs) from Jan 1, 2007, to May 4, 2018, were included in the study. An algorithm was developed based on clinical notes and ICD diagnosis codes. A cohort of 50 patients was included with DIC diagnosis, its variations, and no diagnosis of DIC. Then, the next set of 50 patients was used to refine the algorithm. Results were compared with a manual reviewer and the disagreements were resolved by the third reviewer. The same process was repeated with 'revised clinical note search' for the first and second derivation cohort with additional exclusion terms. The obtained sensitivity and specificity were reported. The generated algorithm was applied to another set of 50 patients for validation. In the first derivation cohort- DIC search by clinical notes and diagnosis codes had 92% sensitivity and 100% specificity. Sensitivity dropped to 71% in the second cohort although specificity remains the same. Therefore, the algorithm was refined to clinical notes search only. The revised search was reapplied to first and second derivation cohorts and results obtained for the first derivation were the same but 91.3% sensitive and 100% specific for the second derivation. The search was locked and applied in the validation cohort with 95.8% sensitivity and 100% specificity, respectively. The revised clinical note based electronic search algorithm was found to be highly sensitive and specific for DIC during the corresponding ICU duration.


Is occupation the "driving force" for tobacco consumption? A cross-sectional study to assess prevalence, patterns, and attitude towards tobacco use among long-distance bus drivers and conductors in Western Maharashtra.
Tobacco use remains a major cause of preventable deaths worldwide. The recent Global Adult Tobacco Survey 2016-2017 has shown the prevalence of tobacco use among Indian population to be 28.6%. In Maharashtra, 35.5% of all adult males either smoke tobacco or use some form of smokeless tobacco. Not much data are available on tobacco use with respect to different occupations in India, though risk of tobacco use is known to be higher among individuals in certain occupations. This cross-sectional descriptive study was conducted among 190 long-distance bus drivers and conductors of long route buses departing from one of the main bus stations of the State Transport Corporation in Pune city. Data were collected using a pretested, structured questionnaire by interview method. Prevalence of tobacco consumption (TC) among the respondents was 55.8% (95% confidence interval; 48.4-63). Among the tobacco users, 54% reported initiation at age <18 years "peer pressure" and "curiosity" were the main reasons for initiation while "feeling alert" and "feeling mature" were reasons for continued use. A large proportion (74.5%) of the respondents expressed their intention to quit tobacco in the near future. Long-distance bus drivers and conductors showed a high prevalence of TC which may be linked to certain occupation-related factors. Targeted tobacco cessation activities at workplaces may be considered as a strategy for better impact of tobacco control activities in India.


The cellular distribution and oxidation state of platinum(II) and platinum(IV) antitumour complexes in cancer cells.
The cellular distribution of platinum in A2780 ovarian cancer cells treated with cisplatin and platinum(IV) complexes with a range of reduction potentials has been examined using elemental analysis (synchrotron radiation-induced X-ray emission). The cellular distribution of platinum(IV) drugs after 24 h is similar to that of cisplatin, consistent with the majority of administered platinum(IV) drugs being reduced. Micro-X-ray absorption near-edge spectra of cells treated with cisplatin and platinum(IV) complexes confirmed the reduction of platinum(IV) to platinum(II). In cells treated, the most difficult to reduce complex, cis, trans, cis-[PtCl(2)(OH)(2)(NH(3))(2)], platinum(IV) was detected in the cells along with platinum(II). The observations are in accordance with the relative ease of reduction of the platinum(IV) complexes used and support the requirement of reduction for activation of platinum(IV) complexes.


Screening for antidiabetic activities.
Screening extracts and drug entities for antidiabetic bioactivity is essentially limited to animal models as the processes leading to hyperglycemia and the complications of diabetes involve more than one organ. Further, in vitro results seldom translate into meaningful in vivo outcomes especially in a disease such as Diabetes Mellitus. In vivo studies on specialized animal models have allowed great progress in tailoring research questions towards individualized genetic and biochemical contributors and their effect on the pathogenesis of the disease processes. Various disease models have been used either through genetic-manipulation (transgenic models) or through chemical induction (disease-induced models). Although there is a surplus of animal models (spontaneous and induced) to study Type I and Type II diabetes, there is no ideal or standard model for studying the individualized effects of various classes of antidiabetic drugs. Rodents, most commonly rats and mice, have been used by researchers as animal models of the disease and both normoglycemic and diabetic animals are used to assess the antidiabetic activities of drugs or extracts under investigation. Screening for antidiabetic activities can be achieved by measuring a wide range of biomarkers and end points including blood glucose and insulin levels.


Alexithymia and emotional awareness in anorexia nervosa: time for a shift in the measurement of the concept?
The present study compared 35 patients with anorexia nervosa (AN) with an age matched control group using the Toronto Alexithymia Scale (TAS-20; a self-report instrument) and the Levels of Emotional Awareness Scale (LEAS; a performance-based instrument). Depression and anxiety have been shown to account for elevated levels of alexithymia in AN, and an elevated level of perfectionism might affect self-reporting in general. The AN-group reported a higher level of alexithymia on the TAS-20 compared to the control group, a difference that disappeared after controlling for depression or anxiety (but not for perfectionism). The findings suggest that the AN-patients believe that they have difficulties in identifying and reporting emotions, but actually perform as well as the control group when confronted with the task of identifying and reporting their emotions according to LEAS. It might be time to rethink the measurement of alexithymia. Maybe, similar to assessment of personality disorders, it should not be assessed when patients are depressed, or it should be assessed through instruments and modalities that are not sensitive to the mood state of the patient.


The state of hormonal contraception today: benefits and risks of hormonal contraceptives: progestin-only contraceptives.
The progestin component of hormonal contraceptives accounts for most of their contraceptive effects. Several dosage forms of progestin-only contraceptives have been developed, including pills, injectables, implants, and intrauterine devices. Emergency contraceptives may also contain progestin only and are indicated for prevention of pregnancy following unprotected intercourse or contraceptive failure. Each form has benefits, some specific to the form. An understanding of benefits and risks allows clinicians a wider choice when recommending effective hormonal contraception.


Xenotransplantation: Where Are We with Potential Kidney Recipients? Recent Progress and Potential Future Clinical Trials.
Inter-species transplantation, xenotransplantation, is becoming a realistic strategy to solve the organ shortage crisis. Here we focus on seminal publications that have driven research in xenotransplantation, as well as recently published literature and future endeavors. Advances in gene editing technology have allowed for the efficient production of multi-transgenic porcine donors leading improved xenograft survival in baboons, up to 2-years following heterotopic heart xenotransplantation and from weeks to several months following life-supporting kidney xenotransplanation. As technology evolves, additional challenges have arisen, including the development of proteinuria, early graft loss associated with porcine CMV, disparities in organ growth between donors and recipients as well as high-dose continuous immunosuppression requirements. To address these issues, our laboratory developed a tolerance-inducing protocol which has allowed for >6 months survival of a life-supporting kidney with further approaches currently underway to address the challenges mentioned above. Our recent findings, reviewed in this article, led us to develop methods to overcome obstacles, which, in conjunction with the work of others, are promising for future clinical applications of xenotransplantation.


The concurrent and longitudinal associations of temperament and nutritional risk factors in early childhood.
Early childhood temperament is increasingly recognized as an important attribute that may impact screen time use, outdoor play and childhood obesity. The relationship between temperament and nutrition in preschool children is less clear. The objective of the study is to investigate if temperament dimensions (negative affectivity, effortful control and surgency) in early childhood are associated with nutritional risk factors. Six hundred seventy-eight children were followed (mean age at baseline visit 3.1 years; mean time to follow-up 16.5 months). Parents reported on child temperament and nutritional risk factors during regularly scheduled well-child clinic visits. A mixed effect model demonstrated a significant association between higher negative affectivity (1.03; 95% CI 0.69 to 1.37) and higher effortful control (-0.88; 95% CI -1.27 to -0.49) on concurrent nutritional risk, independent of covariates. Multivariate linear regression analysis identified that higher effortful control, and not negative affectivity, was significantly associated with a decrease in nutritional risk (-0.67; 95% CI -1.10 to -0.24) over time, independent of covariates. There was no relationship identified between surgency and nutritional risk. Three-year-old children with higher effortful control had reduced nutritional risk at 5 years of age. Future nutritional risk prevention strategies may benefit from interventions to increase effortful control in early childhood.


Self-Chargeable Flexible Solid-State Supercapacitors for Wearable Electronics.
Flexible supercapacitors (SCs) always face the charging issue when they are used in some special situations (e.g., wilderness island) that cannot provide electricity, which would limit the continuous energy supply for the attached wearable electronics. Herein, a self-chargeable flexible solid-state supercapacitor (FSSSC) was creatively constructed by sandwiching a piezoelectric polyvinyl alcohol/potassium hydroxide/barium titanate electrolyte between symmetric NiCo2O4@activated carbon cloth electrodes. By virtue of the efficient synergy of each component in the FSSSC, the device exhibits integrated merits with excellent flexibility, satisfactory electrochemical properties, and considerable self-charging capability through synchronously collecting and converting mechanical energy (e.g., repeated bending) into storable electrochemical energy in a persistent way. When the devices are serially connected and self-charged, they can be used to drive typical electronics with normal working. Such a unique material and device design enables the FSSSC with combined capabilities such as energy-harvesting and conversion and storage device for self-powered wearable electronics.


A newly identified polysaccharide from Ganoderma atrum attenuates hyperglycemia and hyperlipidemia.
A polysaccharide from Ganoderma atrum (PSG-1) was purified and characterized, and its hypoglycemic and hypolipidemic effects were investigated in high fat diet- and streptozotocin-induced type 2 diabetic rats. Oral administration of PSG-1 at 200 or 400 mg/kg body weight significantly reduced fasting blood glucose and serum insulin levels. PSG-1 significantly decreased the levels of serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, free fatty acid and insulin resistance, and increased high-density lipoprotein cholesterol level and insulin sensitivity. In addition, PSG-1 inhibited the expression of pro-apoptotic protein, Bax and increased the expression of anti-apoptotic protein, Bcl-2 in pancreatic cells, suggesting that PSG-1 exerted a protective role in the pancreas of diabetic rats. These results indicated that PSG-1 may have a potential for the treatment of hyperglycemia, hyperlipidemia, hyperinsulinemia and insulin resistance in type 2 diabetes.


Haloxyfop-P-methyl induces immunotoxicity and glucose metabolism disorders and affects the Nrf2/ARE pathway mediated antioxidant system in Chiromantes dehaani.
Haloxyfop-P-methyl is used extensively in agricultural production, and its metabolites in soil have potentially toxic effects on aquatic ecosystems. In this study, we explored the toxicity of haloxyfop-P-methyl on Chiromantes dehaani. The results of the 21-day toxicity test showed that haloxyfop-P-methyl decreased the weight gain (WG), specific growth rate (SGR) and hepatosomatic index (HSI). In glucose metabolism, haloxyfop-P-methyl reduced pyruvate, lactate, lactate dehydrogenase and succinate dehydrogenase, but enhanced glucose-6-phosphate dehydrogenase and hexokinase. Furthermore, expression of glucose metabolism-related genes was upregulated. We cloned the full-length CdG6PDH gene, which contains a 1587 bp ORF that encoded a 528 amino acid polypeptide. In antioxidant system, haloxyfop-P-methyl increased glutathione, thioredoxin reductase and thioredoxin peroxidase activities and activated the Nrf2/ARE pathway through upregulation of ERK, JNK, PKC and Nrf2. In immunity, low concentrations haloxyfop-P-methyl, or short-term exposure, upregulated the expression of immune-related genes and enhanced immune-related enzymes activity, while high concentrations or long-term exposure inhibited immune function. In summary, haloxyfop-P-methyl inhibited the growth performance, disrupted glucose metabolism, activated the antioxidant system, and led to immunotoxicity. The results deepen our understanding of the toxicity mechanism of haloxyfop-P-methyl and provide basic biological data for the comprehensive assessment of the risk of haloxyfop-P-methyl to the environment and humans.


Synonymous codon usage pattern in glycoprotein gene of rabies virus.
Rabies virus (RABV) is the causative agent of a fatal nervous system ailment. The disease is zoonotic and prevalent in many developing countries. The glycoprotein (G) of RABV is the major antigenic determinant of the virus and plays a pivotal role in its neurovirulence. Various aspects of 'G' protein biology have been explored, but the factors affecting the nucleotide choice and synonymous codon usage have never been reported. In the present study, we have analyzed the relative synonymous codon usage and effective number of codons (Nc) using 132 'G' protein genes of RABV. Corresponding analysis was used to calculate major trends in codon usage. The correlation between base composition and codon usage as well as the plot between Nc and GC3 suggest that mutational pressure is the major factor that influences the codon usage in the G gene of RABV. In addition, factors like aromaticity, aliphatic index and hydropathy have shown slight correlation suggesting that natural selection also contributes to the codon usage variations of the 'G' gene. In conclusion, codon usage bias in 'G' gene of RABV is mainly by mutational pressure and natural selection.


African Swine Fever (ASF) Trend Analysis in Wild Boar in Poland (2014-2020).
African swine fever (ASF) is a lethal hemorrhagic disease of Suidae, i.e., domestic pigs and wild boars. The disease was introduced to Poland in 2014 and is now present in the wild boar population. Appropriate ASF prevention requires further research for answers to fundamental questions about the importance of vectors in virus transmission, the impact of environmental factors on the presence of ASFV in wild boar habitats, and the role of survivors as potential virus carriers and their part in the potential endemicity of ASF. In order to analyze the changes in the molecular and serological prevalence of ASFV in wild boar population in Poland, real-time PCR and ELISA/IPT tests were conducted. In the analyzed period (2014-2020), most of the ASF-positive wild boars were molecular/virus-positive, however, over the years the percentage and the number of seropositive animals has increased. At the beginning of the epidemic, the disease was limited to a small area of the country. Since then, it has spread to new provinces of Poland. From the beginning and until today, most notifications of ASF-positive wild boars were for carcasses (passive surveillance), however, the number of serologically positive animals is still increasing. Despite the fact that notifications of ASF outbreaks are still being received near the eastern border of Poland, the old ASF area seems to be limited mainly to ASF serologically positive animals, which may indicate the beginning of ASF endemicity in Poland.


Assessing the relative efficacy of antiretroviral activity of different drugs on macrophages.
HIV-infected monocyte/macrophage-derived cells are believed to play a major role in the spread of HIV through the body. Not only are fresh monocytes and more differentiated macrophages relatively insensitive to the cytopathic effect of HIV, but once infected they can efficiently infect T-cells. The protocols in this chapter can be used to culture HIV in monocytes/macrophages and to study factors such as drugs and chemokines that influence its replication. Support protocols describe the 6-d-adherence method for preparing mature monocytes/macrophages, a quick and simple means of obtaining mature cells for routine HIV-infection studies, as well as methods for quantitation of HIV in monocytes/macrophages.


Phantom and animal studies of a new hepatobiliary agent for MR imaging: comparison of Gd-DTPA-DeA with Gd-EOB-DTPA.
To investigate the characteristics of Gd-DTPA-DeA as a hepatobiliary contrast agent for MR imaging in comparison with those of Gd-EOB-DTPA. We undertook phantom experiments to assess T1 relaxivity for Gd-DTPA-DeA, Gd-EOB-DTPA, and Gd-DTPA in human plasma. For Gd-DTPA-DeA and Gd-EOB-DTPA, we evaluated the contrast effect in rats using an SPGR sequence. The contrast ratios of liver and abdominal aorta were measured up to 21 minutes after intravenous administration of the agents. Visualization of the bile duct and renal pelvis was also assessed. In human plasma, T1 relaxivity was similar for Gd-DTPA-DeA and Gd-EOB-DTPA, and higher than those for Gd-DTPA. Whereas the contrast ratio of liver peaked about five minutes after the injection of Gd-EOB-DTPA and was followed by a subsequent decline, a continuous rise was shown for Gd-DTPA-DeA, resulting in a larger maximal contrast effect. Contrast ratios of the abdominal aorta were larger for Gd-DTPA-DeA. Biliary excretion was observed for both agents but occurred earlier with Gd-EOB-DTPA. While renal excretion was shown for all rats three minutes after the injection of Gd-EOB-DTPA, it was not observed for Gd-DTPA-DeA. Gd-DTPA-DeA may be used as a hepatobiliary contrast agent and shows different pharmacokinetics from Gd-EOB-DTPA.


Analysis of protein phosphorylation in human neutrophils.
Polymorphonuclear neutrophils play a key role in host defense and inflammation. Neutrophils can be activated by a variety of soluble and particulate factors, leading to an increase in the phosphorylation of numerous proteins on tyrosines, serines and threonines. Upon covalent binding of phosphates to these amino acids, the charge and conformation of the corresponding proteins are modified, generally leading to changes in protein functions such as protein-protein interactions and enzymatic activity. Protein phosphorylation in neutrophils can be studied by following protein incorporation of radiolabeled inorganic phosphate. This technique is based on labeling the intracellular ATP pool with 32P prior to applying a stimulus that induces changes in protein phosphorylation status. The proteins are extracted from the cells, immunoprecipitated or not, resolved on polyacrylamide gel electrophoresis, then transferred onto nitrocellulose membranes and visualized by means of autoradiography. Phosphorylated sites of a multisite-phosphorylated protein can be analyzed by using two-dimensional tryptic phosphopeptide mapping. This chapter describes a phosphorylation protocol and the analysis of the phosphorylation of a neutrophil protein, p47phox, by two-dimensional tryptic phosphopeptide mapping.


Postnatal development of intra-epithelial leukocytes in the chicken digestive tract: phenotypical characterization in situ.
In the present study, we characterized intra-epithelial leukocytes in the digestive tract of chickens during postnatal development. Their phenotype was characterized by monoclonal antibodies in cryostat sections and the numbers of the different cell-types were counted in the epithelium of the esophagus, proventriculus, duodenum, jejunum, cecum, and colon. All intra-epithelial leukocytes bore the leukocyte-common antigen CD45; 35% were T lymphocytes, and 50% bore a B-cell marker. However, no immunoglobulin-bearing cells were detected in the epithelium. Monocytes and macrophages were found only in the epithelium of the esophagus. A remaining population of non-B, non-T, non-monocyte cells (15%) was present in all parts of the digestive tract. The number of intra-epithelial leukocytes was greatest in the duodenum and jejunum, and decreased in the proximal part of the cecum and in the colon. Intra-epithelial leukocytes were only sporadically detected in the proventriculus. The total number of intra-epithelial leukocytes increased until 8 weeks after hatching and then decreased at 18 months. In the esophagus, the total number of intra-epithelial leukocytes changed little during aging. We found that the intra-epithelial leukocytes of chickens and rodents are distinct in that chicken intra-epithelial leukocytes comprise a cell population that bears a B-cell antigen but that lacks surface immunoglobulins.


Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction.
Monoamine oxidase inhibitors (MAOI) are known to cause serotonin toxicity (ST) when administered with selective serotonin reuptake inhibitors (SSRI). Methylene blue (methylthionium chloride, MB), a redox dye in clinical use, has been reported to precipitate ST in patients using SSRI. MB was assessed for MAO inhibition and so for its potential to precipitate ST. Inhibition of purified human MAO was quantified using kinetic assays and visible spectral changes to study the interactions of MB with MAO A. MB was a potent (tight binding) inhibitor for MAO A. It also inhibited MAO B but at much higher concentration. Interactions of MB with the active site of MAO A were confirmed by its action both as an oxidising substrate and as a one-electron reductant. MB is a potent reversible inhibitor of MAO A with implications for gut uptake of amines when administered orally. At concentrations reported in the literature after intravenous administration, MAO B would be partially inhibited but MAO A would be completely inhibited. This inhibition of MAO A would be expected to lead to perturbations of 5-hydroxytryptamine metabolism and hence account for ST occurring when administered to patients on SSRI treatment.


A review of the role of radiation therapy in the treatment of non-hodgkin lymphomas.
Until recently, non-Hodgkin lymphoma has been difficult to understand. This was due to a lack of appreciation for histologic types, their sub-classifications, modes of spread, and sites of recurrence.The treatment of choice for stage I-II disease is radiation therapy. The value of irradiating adjacent uninvolved node areas or the more extensive Hodgkin-type mantle or inverted "Y" fields is uncertain.Most patients already have reached stage III or IV when first seen. Stage III cases should be treated by a combination of radiation therapy and chemotherapy. There are protocol studies evaluating the role of chemotherapy alone in stage III disease. The primary treatment of stage IV disease probably should be chemotherapy followed by radiation therapy to involved areas or to residual bulky disease.


Which Symptoms of Depression and Anxiety Matter Most? An Investigation of Subjective Importance Ratings With College Students in India.
One goal of clinical psychological science is to help people with problems that matter to them. However, little is known about which kinds of symptoms are viewed as most important, particularly among individuals in non-western settings. We examined the extent to which young adults in India rated individual symptoms of depression and anxiety as important, concerning, and undesirable. Participants were college students at Indian Universities (n = 283). They received a measure of depressive symptoms (Patient Health Questionnaire-9) and anxiety symptoms (Generalized Anxiety Disorder Screener-7). For each of the 16 symptoms, they provided three judgments relating to the extent to which they found the symptom important, harmful, and undesirable. These judgments were averaged to form a "subjective importance rating" (SIR) for each symptom. Anxiety symptoms were viewed as more important than depressive symptoms (d = 0.34), and nonsomatic symptoms were viewed as more important than somatic symptoms (d = 0.83). Females rated symptoms as more important than males (d = 0.32), and individuals with higher self-reported symptoms rated symptoms as more important. Sad mood, suicidal ideation, and controlling worries were rated as the most important symptoms, whereas concentration problems, appetite problems, and psychomotor problems were rated as the least important. Overall, some symptoms are viewed as more important and concerning than others. We discuss how this understanding can affect our conceptualization, assessment, and treatment of mental disorders around the world.


Structural and replicative forms of mitochondrial DNA from human leukocytes in relation to age.
The structure and replication of human leukocyte mitochondrial DNA (mtDNA) was investigated in healthy young adult males (23--37 years old), middle-aged males (42--52 years old) with secondary polycythemia, and elderly males (80--89 years old) who exhibited different degrees of age-related disease syndromes. The distribution of the various cell types within the white cell population was within normal limits in all samples. Total mtDNA was isolated in ethidium bromide--CsCl gradients and examined by electron microscopy after spreading by the aqueous and formamide techniques. The individual frequencies of catenated forms ranged from 2 to 6% but showed relatively little change (declining slightly) with age. The individual frequencies of circular dimers varied from 0 to 0.1% in the young adult and polycythemic groups and in 10 out of 12 elderly individuals. One elderly individual had a circular dimer frequency of 0.3% (including a circular molecular of tetramer size) and another had 4.5%. This finding suggest that agerelated cellular pathology may exist in the blood-forming system in some cases. The mode of replication of leukocyte mtDNA agrees well with that described for mouse L cells. There was no evidence of aberrant mtDNA replication as a result of aging.


rBaltMIP, a recombinant alpha-type myotoxin inhibitor from Bothrops alternatus (Rhinocerophis alternatus) snake, as a potential candidate to complement the antivenom therapy.
Phospholipase A2 inhibitors (PLIs) are important targets in the search and development of new drugs. This study aimed at evaluating the potential of an alpha-type phospholipase A2 inhibitor from Bothrops alternatus (Rhinocerophis alternatus) snake in its recombinant form (rBaltMIP) to complement the conventional antivenom therapy. Biochemical experiments showed that rBaltMIP presented pI 5.8 and molecular masses of ∼21 kDa by SDS-PAGE and 19.57 kDa by MALDI/TOF MS. After tryptic peptides sequencing, the results were compared with other PLIs available in databases, showing 100% identity between rBaltMIP and its native inhibitor BaltMIP and from 92% to 96% identity with other inhibitors. Myotoxic activities of BthTX-I and BthTX-II toxins were measured via plasma CK levels, showing myotoxic effective concentrations (EC50) of 0.1256 μg/μL and 0.6183 μg/μL, respectively. rBaltMIP neutralized the myotoxicity caused by these two toxins up to 65%, without promoting primary antibody response against itself. Nevertheless, this recombinant PLI was immunogenic when standard immunization protocol with Freud's adjuvant was used. In paw edema assays, EC50 of 0.02581 μg/μL and 0.02810 μg/μL, respectively, were observed with edema reductions of up to 40% by rBaltMIP, suggesting its use as an additional antivenom. In addition, myotoxicity neutralization experiments with the myotoxin BthTX-I showed that rBaltMIP was more effective in inhibiting muscle damage than the conventional antivenom. Thus, considering the severity of envenomations due to Bothrops alternatus (Rhinocerophis alternatus) and the low neutralization of their local effects (such as myotoxicity) by the current antivenoms, rBaltMIP is a promising molecule for the development of novel therapeutic strategies for clinical applications.


Is Formal Research Training Associated With Academic Success in Oral and Maxillofacial Surgery?
Pursuing promotion in academic rank and seeking funded research opportunities are core elements of academic practice. Our purpose was to assess whether formal research training influences academic rank or National Institutes of Health (NIH) funding among full-time academic oral and maxillofacial surgeons (OMSs). We performed a cross-sectional study of full-time academic OMSs in the United States. The primary predictor variable was completion of formal research training, defined as a research fellowship or advanced non-clinical doctoral research degree (PhD, DMSc, DPH, DPhil, ScD). The outcomes measures were current academic rank and successful acquisition of NIH funding (yes vs no). Other study variables included MD degree, clinical fellowship training, years since training completion, and Hirsch index (H-index), a measure of academic productivity. We computed the descriptive, bivariate, and multiple regression models and set P ≤ .05 as significant. A total of 299 full-time academic OMSs were included in the study sample. Of the 299 OMSs, 41 (13.7%) had had formal research training. Surgeons with formal research training had a greater mean interval since completion of training (P = 0.01) and had a greater mean H-index (P = 0.02). Formal research training was not associated with academic rank (P = .10) but was associated with an increased likelihood of receiving NIH funding (P < .001). In a multiple logistic regression model, after adjusting for years since completing training and H-index, formal research training was associated with an increased likelihood of obtaining NIH funding (odds ratio, 3.22; 95% confidence interval, 1.15 to 9.00; P = .03). Among academic OMSs, those with formal research training had greater success with obtaining NIH funding. However, formal research training did not appear to influence an OMS's current academic rank.


Neural architecture of the brachiolaria larva of the starfish, Asterina pectinifera.
The nervous system of the brachiolaria larva of the starfish, Asterina pectinifera, was characterized using immunohistochemistry with the neuron-specific monoclonal antibodies 1E11 and 1F9 and an anti-serotonin antibody. The antigen recognized by 1F9 was determined by immunoprecipitation, peptide identification by mass spectrometry, and cDNA cloning as a novel START (steroidogenic acute regulatory protein [StAR]-related lipid transfer) domain-containing protein. Nerve cells are prominent in the brachiolar arms, ciliary bands, and adult rudiment. The brachiolar arms contain sensory-like nerve cells in the adhesive papillae, flask-shaped nerve cells in the adhesive disk, and bundles of fibers with branches interconnecting them. In the ciliary bands, nerve cells are interconnected with axon bundles along the ciliary bands and some neurons send fibers toward the oral and aboral epidermis. These neural components of the ciliary bands are regionally modified to form masses such as lateral and oral ganglia. The future aboral epidermis of the adult rudiment forms a nerve plexus with cell bodies enriched over spicules. Serotonergic nerve cell bodies are found throughout the nervous system except in the adhesive disk, the bipinnaria arms, and the adult rudiment. In addition, there are neural components in the esophagus and in the coelom where nerve fibers or bundles have distinct orientations with respect to the muscle fibers. The neuroanatomy of the brachiolaria suggests how it may function in controlling larval physiology and identifies intriguing problems on the origin of larval and adult nerves.


The oculo-auriculo-fronto-nasal syndrome (OAFNS) - description of a rare and complex craniofacial deformity and its interdisciplinary management before school age.
Craniofacial clefts are certainly among the most challenging congenital malformations with respect to functional, aesthetic and psychosocial consequences. The aetiology is still under discussion, recent molecular genetic findings suggest defects in the ciliary function of neural crest cells during facial development. The severity of craniofacial clefting is known to be extremely variable. Different classifications have been proposed however nomenclature is not uniform. If vertical, median craniofacial clefting of fronto-naso-maxillary structures is accompanied by auriculo-mandibular malformations the term oculo-auriculo-fronto-nasal syndrome (OAFNS) has been proposed. Extreme craniofacial abnormalities have to be expected in this rare disorder. Adequate correction is a surgical challenge and interventions have to be adapted individually to patient's needs with respect to general condition, age and growth. This case report describes both the underlying pathology as well as the interdisciplinary management of a female patient from birth to 6 years of age affected by this rare combination of vertical craniofacial clefting and bilateral auriculo-mandibular dysplasia.


Prognostic value of pre-treatment lymphocyte count and T cell levels in localized bronchogenic carcinoma.
In the patient with clinically localized bronchogenic carcinoma, the pre-treatment peripheral blood lymphocyte count and the thymus-dependent lymphocyte (T cell) level correlated with the prognosis of the tumor histology was either squamous cell, oat cell, or undifferentiated carcinoma. Patients whose pre-treatment lymphocyte count was less than 1,000/ml or whose T cell level was less than 750/ml either died or developed distant metastases by nine months after treatment of their localized tumor. By contrast, 55% of patients whose pre-treatment T cell level was greater than 750/ml were alive and without evidence of metastases nine months after treatment (P less than 0.02). Analysis of survival of these patients by the life-table method through the first post-treatment year further demonstrates the prognostic value of a low pre-treatment lymphocyte count or T cell level. The pre-treatment lymphocyte count and T cell level in patients with adenocarcinoma did not correlate with prognosis.


Use of health services and unmet needs among adults with cerebral palsy in Ireland.
To describe use of health services, unmet needs relating to health services, and identify factors associated with service use among adults with cerebral palsy (CP) in Ireland. Data relating to demographics, secondary diagnoses, current use of health services and assistive devices, and unmet needs for both were obtained on adults with CP from the National Physical and Sensory Disability Database. Logistic regression was used to identify factors associated with service use. A total of 1268 adults with CP were included in this study. Over half were male (56%) and 78% lived with parents, siblings, or other family relatives. Physiotherapy, occupational therapy, and orthotics/prosthetic services were the most commonly used services, used by 57%, 48%, and 35% of the sample respectively. Unmet needs were highest for physiotherapy (23%) and occupational therapy services (13%). Age, sex, living arrangements, and wheelchair use were frequently associated with current service use. Adults with CP used a wide range of health services and unmet needs were reported for all services. The findings highlight a need for planning and development of services to meet their needs, regardless of their age, mobility level, or living arrangements. Adults with cerebral palsy (CP) in Ireland used a wide range of therapeutic, respite, personal assistance, and support services. Unmet needs were highest for physiotherapy and occupational therapy services. Adults aged 25 years and above were less likely to use therapy services compared with younger adults. Adults living with parents, siblings, or family relatives were less likely to use personal assistance and physiotherapy services.


A simple treatment of post-lumbar-puncture headache.
We report a case of post-lumbar-puncture headache successfully treated with intravenous caffeine sodium benzoate. The patient presented to the emergency department with a severe headache three days after a myelogram of the lumbar region. Caffeine sodium benzoate (500 mg) in 1 liter of fluid (D5LR) intravenously over one and a half hours was administered. The patient reported complete resolution of symptoms and no recurrence of headache. Caffeine sodium benzoate is a simple treatment of post-lumbar-puncture headaches. It should be considered as a safe alternative to an epidural blood patch for the treatment of post-lumbar-puncture headaches.


Utility of Postoperative Serial Renal Function Monitoring in Patients Undergoing Radical Cystectomy for Urothelial Carcinoma.
The aim of this study is to examine the rates of clinical actions (CAs) as a result of serial creatinine (SCr) values and to examine postoperative SCr trends to assess the utility of SCr measurements in radical cystectomy (RC) patients. We performed a retrospective chart review using our institution's database on all patients who underwent radical cystectomy for urothelial carcinoma (UC) from 2009 to 2019. Preoperative and all postoperative inpatient creatinine values were recorded. Minor CAs included fluid boluses, fluid rate changes, and medication changes. Major CAs included OR take-backs for stent repositioning, nephrostomy tube placement, nephrology consultation, and hemodialysis. A total of 238 RCs were performed with a resultant 2952 SCr measurements. The median number of SCr measurements per patient was 9 (interquartile range, IQR 7) with median length of hospital stay of 10 days (IQR 9 days). There were 92 minor and 12 major CAs as a result of 3% and 0.44% of SCr measurements, respectively. All major CAs were seen in patients experiencing complicated postoperative course. The median postoperative day with the highest creatinine was day 2. Predictors of postoperative CAs included preoperative renal dysfunction and obesity. SCr measurements remain a clinically valuable tool in postoperative management. Nonetheless, this present study suggests that prolonged SCr monitoring is of limited clinical utility. As such, discontinuing SCr checks after postoperative day 3 in patients experiencing uncomplicated postoperative course is safe and may lead to both cost savings and decreased patient discomfort.


Selective effects of TPA and IL-1 on protein phosphorylation in murine thymocytes.
Protein kinase C activity was demonstrated in murine thymocytes and the effects of TPA and IL-1 on this enzyme were studied. TPA, but not IL-1, could substitute for diacylglycerol in protein kinase C activation. Although TPA and IL-1 are both potent comitogens for murine thymocytes they markedly differ in their effects on protein phosphorylation and protein kinase C activation. Treatment of intact thymocytes with TPA resulted in a marked increase in the phosphorylation of an endogenous protein with Mr approximately 44,000. Enhanced phosphorylation of this protein was also observed when protein kinase C was activated in thymocyte extracts. In contrast to TPA, IL-1 neither induced phosphorylation of the 44,000-Da protein nor activated protein kinase C. The data suggests that protein kinase C does not mediate the comitogenic effect of IL-1 in murine thymocytes.


The influence of specialists on prescribing by GPs. A qualitative study.
To investigate specialists' influence on prescribing by general practitioners. A focus group study of 35 GPs. Hunter Urban Division of General Practice, New South Wales. Although GPs thought specialists had only a small influence on their prescribing overall, it was substantial in some clinical areas, in complex conditions and conditions seen infrequently. Specialists were seen as authoritative and unbiased. Local specialists were particularly influential. Specialist influence came from seeing how specialists managed patients, clinical meetings, and specific verbal advice. It influenced the prescribing of new drugs, selection of drugs within a class and sometimes changed established prescribing practices. Interventions to change GPs' prescribing practices should address the importance of specialist influence, and not focus on GPs alone.


Genotoxic effects of some organophosphorus pesticides. II. In vivo chromosomal aberration bioassay in bone marrow cells in rat.
The genotoxic effects of 4 organophosphorus pesticides, i.e., ekatin, fenitrothion, methylparathion and phorate, were assessed employing in vivo chromosomal aberration bioassay in bone marrow cells in rat. Methylparathion and phorate were found to be mutagenic while ekatin was weakly mutagenic. The frequency of chromosomal aberrations induced by fenitrothion did not differ significantly from that observed in negative control.


Role of neuronal nitric oxide synthase in the antiallodynic effects of intrathecal EGCG in a neuropathic pain rat model.
Epigallocatechin-3-gallate (EGCG), the major catechin in green tea, is known to have antioxidant activity against nitric oxide (NO) by scavenging free radicals, chelating metal ions, and inducing endogenous antioxidant enzymes. NO and NO synthase (NOS) play an important role in nociceptive processing. In this study, we examined the effects of intrathecal EGCG in neuropathic pain induced by spinal nerve ligation and the possible involvement of NO. Intrathecal EGCG attenuated mechanical allodynia in spinal nerve ligated-rats, compared to sham-operated rats, with a maximal possible effect of 69.2%. This antinociceptive effect was reversed by intrathecal pretreatment with l-arginine, a precursor of NO. Intrathecal EGCG also blocked the increase in nNOS expression in the spinal cord of spinal nerve-ligated rats, but iNOS expression was not significantly suppressed. These findings suggest that intrathecal EGCG could produce an antiallodynic effect against spinal nerve ligation-induced neuropathic pain, mediated by blockade of nNOS protein expression and inhibition of the pronociceptive effects of NO.


Lactobacillus uvarum sp. nov.--a new lactic acid bacterium isolated from Spanish Bobal grape must.
Five strains isolated from grape musts in Spain in 1997, have been characterized by several molecular techniques, and three of them have been identified as pertaining to a new species. All strains are Gram-positive rods, aerotolerant and homofermentative bacteria that do not exhibit catalase activity. Phylogenetic analysis based on 16S rRNA gene sequences placed these strains within the genus Lactobacillus, closely related to Lactobacillus mali. DNA-DNA hybridization experiments confirmed that strain 71 belongs to the lately described species L. satsumensis, strain 88 belongs to L. mali and the other three isolates have an independent status at species level. Restriction analysis of the amplified 16S rRNA gene (16S-ARDRA), internal spacer region (ISR) analysis, random amplified polymorphism DNA (RAPD) and ribotyping were performed in order to establish genotypic similarities and differences between the new species and their closest species. The three isolates can be genetically differentiated from their closest relatives by RAPD analysis and ribotyping. Phenotypically, they can be distinguished by several traits such as their ability to grow at pH 3.3 and NaCl 5% (w/v) and by certain carbohydrate fermentations. The name L. uvarum sp. nov. is proposed. The type strain is 8T (=DSM 19971T = colección española de cultivos tipo (CECT) 7335T).


Caring from a distance: how a COVID-19 visitor ban affects relatives when a loved one is admitted to a neurological or neurosurgical ward.
Neurological patients often suffer physical, cognitive, communicative, behavioural or psychosocial limitations. This may weaken the preconditions for participating in decisions about their treatment, rehabilitation and future. These impairments often cause relatives to care and advocate for the patient. This practice was gravely interrupted by the COVID-19 visitor ban. This study aims to investigate how relatives of neurological patients experienced the visitor ban and to identify potential areas for improvement. Twelve semi-structured interviews with relatives of neurological patients were conducted. Data were analysed by performing a thematic analysis inspired by Braun and Clark. The following six themes emerged: Visitor ban as a necessary evil, Losing control and feeling checkmate, Mending the information gap, Waiting by the phone, Empathy and compassion as the core of a good relationship and Caring for a loved one from a distance. Having a loved one admitted to a neurological ward during the COVID-19 visitor ban greatly restrains relatives and affects the relationship with their loved one and the hospital healthcare staff. Healthcare staff need to take responsibility and reach out, while simultaneously exploring new ways of communicating.


Tankyrase: a promising therapeutic target with pleiotropic action.
Tankyrase 1 (TNKS1) and tankyrase 2 (TNKS2) enzymes belong to the poly (ADP-ribose) polymerase (PARP) family participates in process of poly-ADP-ribosylation of different target proteins which leads to ubiquitin-mediated proteasomal degradation. Tankyrases are also involved in the pathophysiology of many diseases, especially cancer. Their functions include cell cycle homeostasis (primarily in mitosis), telomere maintenance, Wnt signaling pathway regulation, and insulin signaling (particularly GLUT4 translocation). Studies have implicated that genetic changes, mutations in the tankyrase coding sequence, or up regulation and down regulation of tankyrase are reflected in the numerous disease conditions. Investigations are pursued to develop putative molecules that target tankyrase in various diseases such as cancer, obesity, osteoarthritis, fibrosis, cherubism, and diabetes, thereby providing a new therapeutic treatment option. In the present review, we described the structure and function of tankyrase along with its role in different disease conditions. Furthermore, we also presented cumulative experimental evidences of different drugs acting on tankyrase.


Peridynamic modeling of nonlinear surface acoustic waves propagating in orthotropic materials.
Due to the elastic nonlinearity of the material, high-amplitude surface acoustic waves undergo nonlinear evolution during propagation and may lead to material failure. To enable the acoustical quantification of material nonlinearity and strength, a comprehensive understanding of this nonlinear evolution is necessary. This paper presents a novel ordinary state-based nonlinear peridynamic model for the analysis of the nonlinear propagation of surface acoustic waves and brittle fracture in anisotropic elastic media. The relationship between seven peridynamic constants and second- and third-order elastic constants is established. The capability of the developed peridynamic model has been demonstrated by predicting surface strain profiles of surface acoustic waves after propagating in the silicon (111) plane and the 〈112¯〉 direction. On this basis, the nonlinear wave-induced spatially localized dynamic fracture is also studied. The numerical results reproduce the main features of nonlinear surface acoustic waves and fracture observed in experiments.


Mesothelioma associated with commercial use of vermiculite containing Libby amphibole.
To describe asbestos-related mortality among manufacturing workers who expanded and processed Libby vermiculite that contained amphibole fiber. Standardized mortality ratio was calculated for 465 white male workers 31 years after last Libby vermiculite exposure. Two workers died from mesothelioma, resulting in a significantly increased standardized mortality ratio of 10.5 (95% confidence interval, 1.3 to 38.0). These workers were in the upper 10th percentile of cumulative fiber exposure, that is, 43.80 and 47.23 fiber-years/cm, respectively. One additional worker with cumulative fiber exposure of 5.73 fiber-years/cm developed mesothelioma but is not deceased. There were no other significantly increased standardized mortality ratios. Workers expanding and processing Libby vermiculite in a manufacturing setting demonstrated an increased risk for the development of mesothelioma following exposure to the amphibole fiber contained within this vermiculite ore source.


Improved enzymatic saccharification of bulrush via an efficient combination pretreatment.
Glycerol (Gly) was selected as hydrogen-bond-donor for preparing ChCl-based DES (ChCl:Gly), and the mixture of ChCl:Gly (20 wt%) and NaOH (4 wt%) was utilized for combination pretreatment of bulrush at 100 °C for 60 min (severity factor LogRo = 1.78). The effects of DES pretreatment on the chemical composition, microstructure, crystal structure, and cellulase hydrolysis were explored. NaOH-ChCl:Gly could remove lignin (80.1%) and xylan (66.8%), and the enzymatic digestibility of cellulose reached 87.9%. The accessibility of bulrush was apparently increased to 645.2 mg/g after NaOH-ChCl:Gly pretreatment. The hydrophobicity and lignin surface area were reduced to 1.56 L/g and 417 m2/g, respectively. The crystallinity of cellulose was increased from 20.8% to 55.6%, and great changes in surface morphology were observed, which explained the improvement of enzymatic hydrolysis efficiency. Overall, DES combined with alkali treatment could effectively promote the removal of lignin and xylan in bulrush, thus the relative saccharification activity was greatly affected.


A biomaterial-silicon junction for photodetection.
Bio-integrated optoelectronics can be interfaced with biological tissues, thereby offering opportunities for clinical diagnosis and therapy. However, finding a suitable biomaterial-based semiconductor to interface with electronics is still challenging. In this study, a semiconducting layer is assembled comprising a silk protein hydrogel and melanin nanoparticles (NPs). The silk protein hydrogel provides a water-rich environment for the melanin NPs that maximizes their ionic conductivity and bio-friendliness. An efficient photodetector is produced by forming a junction between melanin NP-silk and a p-type Si (p-Si) semiconductor. The observed charge accumulation/transport behavior at the melanin NP-silk/p-Si junction is associated with the ionic conductive state of the melanin NP-silk composite. The melanin NP-silk semiconducting layer is printed as an array on an Si substrate. The photodetector array exhibits uniform photo-response to illumination at various wavelengths, thus providing broadband photodetection. Efficient charge transfer between melanin NP-silk and Si provides fast photo-switching with rise and decay constants of 0.44 s and 0.19 s, respectively. The photodetector with a biotic interface comprising an Ag nanowire-incorporated silk layer as the top contact can operate when underneath biological tissue. The photo-responsive biomaterial-Si semiconductor junction using light as a stimulus offers a bio-friendly and versatile platform for artificial electronic skin/tissue.


Amelioration of ketoconazole in lipid nanoparticles for enhanced antifungal activity and bioavailability through oral administration for management of fungal infections.
Ketoconazole (KZ) is a broad-spectrum imidazole antifungal agent, used in opportunistic systemic fungal infection treatment. Gastrointestinal absorption of this drug is variable and depends on the pH of the absorption site. The objective of the investigation was the development and characterization of (KZ) loaded lipid nanoformulations (KZ-LNFs) such as solid lipid nanoparticles (KZ-SLNs) and nanostructured lipid carriers (KZ-NLCs) that could improve oral bioavailability and enhance antifungal activity through oral delivery. KZ-LNFs were prepared using homogenization aided with the sonication method, using dynasan 116 as solid lipid and castor oil as liquid lipid. Prepared KZ-LNFs were evaluated for physicochemical characteristics and optimized. Optimized KZ-LNFs were further evaluated using X-ray diffractometry (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), stability, and freeze-drying. Furthermore, optimized KZ-LNFs were evaluated for in vitro antifungal efficacy against Candida albicans, and bioavailability studies were carried out in Wistar rats by single oral administration compared with KZ suspension as control formulation (KZ-CS). The optimized KZ-SLN formulation showed particle size and entrapment efficiency of 210.9 ± 3.4 nm and 84.8 ± 1.5 % compared to 167.8 ± 5.8 nm and 95.3 ± 2.0 % for optimized KZ-NLC formulation. XRD complemented and confirmed DSC results, KZ was well entrapped inside the core of carrier systems in a molecularly dispersed state. Furthermore, KZ-LNFs formulations exhibited a spherical shape in SEM. In vitro release studies demonstrated a sustained release profile for KZ from KZ-LNFs over a 24 h. After oral administration of the optimized KZ-containing SLN and NLC formulations, there were 2-folds, 2.4-folds, and 2-folds, 2.7-folds enhancements in Cmax and AUC0→∞, respectively compared with KZ-CS. Both NLC and SLN formulations were stable over three months at 4 °C and 25 °C and showed an enhanced antifungal activity. Overall, SLN and NLC formulations considered as alternative delivery vehicles for KZ oral administration in fungal infections treatment.


Stalking the link between reproduction and aging: After decades of research, it still remains a mystery whether and how reproduction drives the process of aging: After decades of research, it still remains a mystery whether and how reproduction drives the process of aging.
The hypothesis that aging and number of offspring are linked with each other has attracted much attention and research, but evidence for it remains elusive.


Linking surface tension to water polarization with a new hypothesis: The Ling-Damodaran Isotherm.
Studying aqueous solutions of complex (bio)polymers is essential from both theoretical and practical perspectives. To understand the principles that govern the properties of these solutions is pivotal for the study of biological processes, considering that the most distinguished components of the cells are polymers (proteins, nucleic acids). These macromolecular aqueous systems, known as colloids, has raise the interest of scientists in recent years. It is known that several physicochemical properties deviate from ideal behaviour in this kind of solutions and that the physical state of water is different compared to its pure state. Particularly, the surface tension of such mixtures often shows a peculiar profile at semi-dilute and concentrated conditions. Here, we joined the colloidal concept of water polarization (proposed in the Association-Induction Hypothesis) with Damodaran's formalism for surface tension to theoretically derive a compelling mathematical model that explains the behaviour of polymer solutions. We measured the surface tension and osmolarity of different polyethylene oxide solutions and we used the ACDAN fluorescence probe to assess the water dipolar relaxation (polarization) in these mixtures. As a proof of concept, we also studied the influence of these polymer solutions on lipid interfaces. Our isotherm model explains the experimental observations with a unifying view that correlates with other measured properties, such as osmolarity and water dipolar relaxation. This provides a link between interfacial and bulk physicochemical properties of polymer solutions, also giving a new framework for studying the interaction of colloidal systems with lipid membranes interfaces.


Transitive movements in a deafferented man.
It has not been determined if the performance of transitive movement requires sensory feedback from the limb to the brain. We tested a deafferented patient's ability to pantomime, imitate, and use actual objects in both eyes open and eyes closed conditions. Although his performance deteriorated when his eyes were closed, the major error made by this patient was the inability to correctly orient the instrument (or pretended instrument) toward the object of the instrument's action.


An Interpretable Prediction Model for Identifying N7-Methylguanosine Sites Based on XGBoost and SHAP.
Recent studies have increasingly shown that the chemical modification of mRNA plays an important role in the regulation of gene expression. N7-methylguanosine (m7G) is a type of positively-charged mRNA modification that plays an essential role for efficient gene expression and cell viability. However, the research on m7G has received little attention to date. Bioinformatics tools can be applied as auxiliary methods to identify m7G sites in transcriptomes. In this study, we develop a novel interpretable machine learning-based approach termed XG-m7G for the differentiation of m7G sites using the XGBoost algorithm and six different types of sequence-encoding schemes. Both 10-fold and jackknife cross-validation tests indicate that XG-m7G outperforms iRNA-m7G. Moreover, using the powerful SHAP algorithm, this new framework also provides desirable interpretations of the model performance and highlights the most important features for identifying m7G sites. XG-m7G is anticipated to serve as a useful tool and guide for researchers in their future studies of mRNA modification sites.


Routine neuroradiological diagnosis with the EMI 5005 body scanner.
The experience with the EMI 5005 body scanner in the neuroradiological diagnosis of about 500 cerebral and 30 spinal examinations is reported. The advantages and disadvantages of this machine are discussed.


Vaccines for respiratory disease in cattle.
Respiratory disease is one of the most serious disease complexes affecting beef cattle production. For example, it is claimed to cost the UK industry about 70 million pounds per year. It is usually associated with young cattle and can occur in a variety of situations. It is a good example of multifactorial disease in that its aetiology involves both infection by a variety of microorganisms and a number of environmental factors. Several distinct syndromes occur and a number of microorganisms are thought to be important including the bacteria Pasteurella haemolytica type A1, P. multocida, Haemophilus somnus, Corynebacterium pyogenes, Mycoplasma bovis and M. dispar. Of the viruses, bovine herpes virus 1 (BHV1) and respiratory syncytial virus (RSV) are known to be important, the former also causing the specific syndrome, infectious bovine rhinotracheitis (IBR) in addition to its involvement in the pneumonia complex. Other viruses of possible importance include para-influenza 3 (Pi3), adenoviruses, bovine viral diarrhoea (BVD) virus, coronavirus and rhinovirus.


Soil ingestion--a major pathway of heavy metals into livestock grazing contaminated land.
An estimated 4000 km2 of agricultural land in England and Wales has been contaminated in varying degrees by past mining and smelting activities. Contaminants include one or more of the metals Cu, Pb, Zn, Cd and As. Studies conducted in southwest and central England conclude that only a small proportion of these metals are taken up into the leaf material of pasture plants and that plant uptake would not seem to constitute a major pathway to grazing animals. Using the titanium content of faeces as a stable indicator of soil ingestion, we found that grazing cattle involuntarily ingest from 1% to nearly 18% of their dry matter intake as soil; sheep may ingest up to 30%. Soil ingestion varies seasonally and with farm management. Calculations based on soil, plant and faecal analyses show that from 9% to 80% percent of the Pb and 34% to 90% of the As intake into cattle on contaminated land is due to ingested soil.


Autonomic and cardiovascular function in the geriatric patient.
The elderly patient is at an increased risk for hemodynamic instability during anesthesia. The underlying mechanisms are primarily a decrease in the beta-receptor response to stimulation, stiffening of the connective tissue throughout the cardiovascular system, and increased vascular resistance during surgical stress and an increased dependency on cardiac filling. Unfortunately, the ability to maintain a steady preload diminishes with age and in general, changes in blood volume are buffered less effectively. Anesthetic management requires closer monitoring of blood pressure and a greater emphasis on vasomotor tone than on fluid administration when treating hypotension.


Defining the fetal origin of MLL-AF4 infant leukemia highlights specific fatty acid requirements.
Infant MLL-AF4-driven acute lymphoblastic leukemia (ALL) is a devastating disease with dismal prognosis. A lack of understanding of the unique biology of this disease, particularly its prenatal origin, has hindered improvement of survival. We perform multiple RNA sequencing experiments on fetal, neonatal, and adult hematopoietic stem and progenitor cells from human and mouse. This allows definition of a conserved fetal transcriptional signature characterized by a prominent proliferative and oncogenic nature that persists in infant ALL blasts. From this signature, we identify a number of genes in functional validation studies that are critical for survival of MLL-AF4+ ALL cells. Of particular interest are PLK1 because of the readily available inhibitor and ELOVL1, which highlights altered fatty acid metabolism as a feature of infant ALL. We identify which aspects of the disease are residues of its fetal origin and potential disease vulnerabilities.


In vivo transmural potential difference: an early monitor of rejection in small bowel transplantation.
To determine if serial measurements of transmural potential difference (TMPD) can serve as an early monitor of rejection in small bowel transplantation, three groups of rats were studied. The groups are defined as follows: (1) group 1, isolated loop (N = 5): 20 cm of distal jejunum was defunctionalized (Thiry-Vella loop); (2) group 2, isotransplant (N = 5): 20 cm of distal jejunum was isotransplanted between inbred Lewis rats, as a Thiry-Vella loop; the native bowel remained in continuity; (3) group 3, allotransplant (N = 8): allotransplantation as in group 2 but between outbred Sprague-Dawley rats. Using luminal and peritoneal electrodes, TMPD was measured serially every third day. Biopsies of the stoma were taken on the same days for histologic examination of rejection. Group 1 animals (isolated loop) did not show a significant decrease in TMPD from day 1 to day 20. Group 2 (isotransplant animals) had a significant decrease in TMPD as compared with group 1 on day 5 (P less than .01), but by day 8, TMPD returned to baseline. Biopsies in groups 1 and 2 showed no signs of rejection. Group 3 (allotransplant animals) showed a significant decrease in TMPD as compared with group 1 on day 5 (P less than .01). The severity of the histologic signs of rejection parallelled the TMPD decrease throughout the remainder of the study. Monitoring TMPD is a sensitive method of detecting early rejection in small intestine transplantation.


RETINAL ARTERY OCCLUSION IN YOUNG: AN UNUSUAL CASE OF BRANCH RETINAL ARTERY OCCLUSION IN A 6-YEAR-OLD CHILD.
To report a unique case of the branch retinal artery occlusion in a 6-year-old child due to hamartoma. A 6-year-old male child presented with chief complaints of foreign body sensation in the left eye without any significant antecedent history of local or systemic cause. Best-corrected visual acuity in the left eye was 20/20. Fundus biomicroscopy revealed altered fundal reflex in superotemporal quadrant and gliotic tissue (Hamartoma) at the first bifurcation of the superior branch of retinal artery. Phakomatosis were ruled out with pediatrician consultation. All related blood investigations were normal. Optical coherence tomography showed focal thinning and optical coherence tomography angiography showed capillary nonperfusion in the corresponding quadrant of the retina. Fluoroscopy under general anesthesia confirmed the diagnosis. We came to the diagnosis of branch retinal artery occlusion may be because of local compression by the hamartoma. Three factors controls the occurrence of the vascular occlusion according to Virchow that is, hypercoagulability, hemodynamic changes, and endothelial injury/dysfunction. In our patient, external compression causing hemodynamic changes and subsequent endothelial injury/dysfunction, which promotes thrombosis seems to be the cause of the branch retinal artery occlusion. Patient was advised scheduled periodic follow-up.


Non-esterified fatty acid metabolism and postprandial lipaemia.
Non-esterified fatty acids (NEFA, or free fatty acids) are an important metabolic fuel. Both the concentration of NEFA and their flux through the circulation vary widely from hour to hour, reflecting nutritional state and physical activity. Inappropriately elevated plasma NEFA concentrations may have a number of adverse effects on both carbohydrate and lipid metabolism. These adverse effects are likely to be most marked in the postprandial period, when NEFA release from adipose tissue is usually suppressed. Although the regulation of NEFA release in the postabsorptive state is well understood in molecular terms, the predominant pathway for release of NEFA in the postprandial state is the action of lipoprotein lipase (LPL) in adipose tissue capillaries on chylomicron-triacylglycerol (TG). Fatty acids released by LPL may either be sequestered in the adipocytes by esterification, or released as NEFA into the plasma. The regulation of this branch-point, which may be of crucial significance for postprandial metabolism, is not well understood. Factors stimulating tissue retention of fatty acids include insulin and acylation stimulating protein. There is considerable indirect evidence that impaired regulation of this step occurs in insulin resistance and other conditions collectively recognised by an elevated concentration of apolipoprotein B (hyper-apo B). Inappropriate release of NEFA in the postprandial period is likely both to reduce the sensitivity of glucose metabolism to insulin and to accentuate postprandial lipaemia. Further study of the regulation of this pathway is much needed.


Low-dose cytarabine and aclarubicin combined with granulocyte colony-stimulating factor for the treatment of relapsed or primary refractory acute lymphocytic leukemia: a retrospective study of 25 Chinese patients.
Despite improvements in treatment, the prognosis of relapsed or primary refractory acute lymphocytic leukemia (ALL) remains poor, and outcomes are worse in older adults with the short first complete remission (CR). Attainment of the second CR by salvage therapy would improve the survival of these patients and may enable them to undergo curative treatment with allogeneic hematopoietic stem cell transplantation. The fact that there are diverse salvage protocols for these adult patients but without a striking CR-induction efficacy indicates that efforts are still needed to indentify new effective reinduction regimens. In this study, the CAG regimen (cytarabine, 10 mg/m(2) subcutaneously every 12 h on days 1-14; aclarubicin, 5-7 mg/m(2) intravenously daily on days 1-8; and concurrent granulocyte colony-stimulating factor, 200 µg/m(2) /day subcutaneously) was administered to 25 patients with relapsed or refractory ALL, including 11 T-cell ALL (T-ALL) and 14 B-cell (B-ALL) patients (age range, 11-61 years; median age, 26 years), to assess its efficacy as a salvage therapy. One course of the CAG regimen resulted in an overall response [CR or partial remission (PR)] rate of 64%, a CR rate of 56% and generally mild adverse effects. An overall response was observed in all 11 T-ALL patients (10 CR and 1 PR) and 35.7% of B-ALL patients (p = 0.0009). The significant treatment potential of CAG regimen for relapsed or primary refractory ALL, especially for T-ALL patients, described in this report would prepare them for a second CR to pursue longer survival.


The central helicase domain holds the major conformational epitopes of melanoma differentiation-associated gene 5 autoantibodies.
Autoantibodies against MDA5 serve as a biomarker for dermatomyositis (DM) and a risk factor for interstitial lung disease (ILD). MDA5 is a protein responsible for sensing RNA virus infection and activating signalling pathways against it. However, little is known about antigen epitopes on MDA5 autoantibodies. We aimed to determine the interaction of the MDA5 autoantibody-antigen epitope. Cell-based assays (CBAs), immunoprecipitation-immunoblot assays, and various immunoblotting techniques were used in the study. We demonstrate that DM patient autoantibodies recognize MDA5 epitopes in a native conformation-dependent manner. Furthermore, we identified the central helicase domain formed by Hel1, Hel2i, Hel2, and pincer (3Hel) as the major epitopes. As proof of principle, the purified 3Hel efficiently absorbed MDA5 autoantibodies from patient sera through immunoprecipitation-immunoblot assay. Our study uncovers the nature of antigen epitopes on MDA5 and provides guidance for diagnosis and targeted therapeutic approach development.


[Cystectomy in the elderly patient].
Bladder cancer is a carcinoma of the elderly population. The highest incidence of bladder cancer is between the ages of 70 and 80 years old. Radical cystectomy remains the gold standard for muscle invasive bladder cancer treatment. In this article different aspects of radical cystectomy in elderly patients are reviewed. The Pubmed-MEDLINE database was searched using the following keywords: radical, cystectomy, elderly and age.


Permanent tooth agenesis in non-syndromic Robin sequence and cleft palate: prevalence and patterns.
Partial tooth agenesis is frequently observed in Robin sequence. Tooth anomalies are increasingly considered as an extended phenotype of the cleft palate population. The study objective was to compare the prevalence and patterns of tooth agenesis in a group of patients with non-syndromic Robin sequence (ns-RS) and a group with non-syndromic cleft palate (ns-CP). The panoramic radiographs of 115 ns-RS and 191 ns-CP patients were assessed for agenesis of the permanent dentition (excluding third molars) and the patterns recorded using the Tooth Agenesis Code. Partial tooth agenesis was observed in 47.8% of ns-RS and 29.8% of ns-CP patients with a greater prevalence in the mandibula than in the maxilla, particularly in ns-RS. The teeth most frequently absent in both groups were the mandibular second premolars and maxillary lateral incisors. Tooth agenesis was bilateral in two-thirds of affected ns-RS patients and one-half of ns-CP patients. In ns-RS, bilateral agenesis of the mandibular second premolars was more frequently observed in female than that in male patients. Completely symmetrical patterns of hypodontia were found in around 45% of ns-RS patients with tooth agenesis compared to 35% in ns-CP. No association was found between the extent of the palatal cleft and the severity of hypodontia. Tooth agenesis is more prevalent in ns-RS than that in ns-CP, demonstrates a much greater predilection for the mandible in ns-RS, and bears no relation to the extent of the palatal cleft. When compared to ns-CP, additional developmental disturbances are likely involved in the etiology of tooth agenesis in ns-RS. Future research could help identify the underlying genetic traits and aid in classifying patients in those with and without expected tooth agenesis in order to facilitate orthodontic management strategies.


Quality assessment in head and neck oncologic surgery in a Brazilian cancer center compared with MD Anderson Cancer Center benchmarks.
Quality assessment is a major tool for evaluation of health care delivery. In head and neck surgery, the University of Texas MD Anderson Cancer Center (MD Anderson) has defined quality standards by publishing benchmarks. We conducted an analysis of 360 head and neck surgeries performed at the AC Camargo Cancer Center (AC Camargo). The procedures were stratified into low-acuity procedures (LAPs) or high-acuity procedures (HAPs) and outcome indicators where compared to MD Anderson benchmarks. In the 360 cases, there were 332 LAPs (92.2%) and 28 HAPs (7.8%). Patients with any comorbid condition had a higher incidence of negative outcome indicators (p = .005). In the LAPs, we achieved the MD Anderson benchmarks in all outcome indicators. In HAPs, the rate of surgical site infection and length of hospital stay were higher than what is established by the benchmarks. Quality assessment of head and neck surgery is possible and should be disseminated, improving effectiveness in health care delivery. © 2015 Wiley Periodicals, Inc. Head Neck 38: 1002-1007, 2016.


Oxidation of guanines in the iron-responsive element RNA: similar structures from chemical modification and recent NMR studies.
The translation or stability of the mRNAs from ferritin, maconitase, erythroid aminoevulinate synthase and the transferrin receptor is controlled by the binding of two iron regulatory proteins to a family of hairpin-forming RNA sequences called iron-responsive elements (IREs). The determination of high-resolution nuclear magnetic resonance (NMR) structures of IRE variants suggests an unusual hexaloop structure, leading to an intra-loop G-C base pair and a highly exposed loop guanine, and a special internal loop/bulge in the ferritin IRE involving a shift in base pairing not predicted with standard algorithms. Cleavage of synthetic 55- and 30-mer RNA oligonucleotides corresponding to the ferritin IRE with complexes based on oxoruthenium(IV) shows enhanced reactivity at a hexaloop guanine and at a guanine adjacent to the internal loop/bulge with strong protection at a guanine in the internal loop/bulge. These results are consistent with the recent NMR structures. The synthetic 55-mer RNA binds the iron-regulatory protein from rabbit reticulocyte lysates. The DNA analogs of the 55- and 30-mers do not show the same reactivity pattern. The chemical reactivity of the guanines in the ferritin IRE towards oxoruthenium(IV) supports the published NMR structures and the known oxidation chemistry of the metal complexes. The results constitute progress towards developing stand-alone chemical nucleases that reveal significant structural properties and provide results that can ultimately be used to constrain molecular modeling.


Dichotic listening indices of right hemisphere semantic processing.
A new dichotic listening technique, based on a psychophysical threshold procedure and providing ordinal scale measurement of lateral asymmetry, was used to investigate variation in the size of right-ear advantage for verbal vs manual response modalities across three semantic categories of stimuli in 60 right-handed males. For manual responders, abstract words elicited a significantly greater right-ear advantage than did concrete words, while emotional words elicited a non-significant left-ear advantage. Verbal responders showed no significant difference in the size of right-ear advantage across stimuli. The results suggest that both response modality and stimulus type are important variables for dichotic listening paradigms seeking evidence of right hemisphere contributions to semantic processing.