Determinant-regulated onset of experimental autoimmune encephalomyelitis: distinct epitopes of myelin proteolipid protein mediate either acute or delayed disease in SJL/J mice.
In the present study we address the question of whether distinct self-determinants can target alternative autoimmune disease patterns in experimental autoimmune encephalomyelitis (EAE), an animal model widely used for studying multiple sclerosis. We have found that the clinical course of EAE can be determined by the target peptide selected for induction of disease. In SJL/J mice, actively induced and passively transferred EAE mediated by the immunodominant PLP determinants p139-151 and p178-191 consistently produced a rapid onset of severe clinical signs. In contrast, a delayed onset of both active and passive EAE is associated with the nondominant cryptic PLP determinant p104-117. The delayed disease induced with p104-117 is not associated with any unusual peptide feature, with bystander immunoregulation, with inept class II MHC binding, or with failure to induce T cell expression of CD44, VLA-4, or IL-2 receptor upon activation. However, delayed disease is associated with innate qualities of the T cell repertoire responding to the p104-117 determinant. T cell lines responding to the cryptic p104-117 show limited TCR-V beta utilization compared to the diverse repertoire responding to the dominant p139-151 determinant. The repertoire deletions are accompanied by low level production of pathogenic Th1 cytokines (IFN gamma; IL-2) and increased production of regulatory Th2 (IL-4) cytokine in activated p104-117 primed T cells. Thus, the delayed encephalitogenicity of p104-117 may be due to TCR-V beta deletions and activation defects in the responding T cell repertoire. The development of "slow disease" mediated by autoreactivity against hidden self-determinants may have important implications in the pathogenesis of both relapsing and chronic autoimmune demyelinating disease.


Study of the applicability of Sponge City concepts for flood mitigation based on LID (low impact development) measures: A case study in Conakry City, Republic of Guinea.
Urban flooding is becoming a significant urban epidemic in many nations throughout the world as a result of land use and climate change, and regular heavy rains. In this study, we choose to investigate the viability of Sponge City concepts for flood mitigation based on low impact development (LID) strategies in a 26.66 km2 area situated in Guinea's capital city of Conakry. The Storm Water Management Model (SWMM5) was used to simulate the impact of LID measures on the lowering of runoff peaks and node flooding. Simulation results before and after LID facilities are compared in order to understand how LID measures improve flood mitigation. The study showed that LID techniques effectively reduce runoff, which helps mitigate the effects of flooding. The study demonstrated that all LID, whether used singly or in combination, can lower runoff and flooding. However, when it comes to reducing runoff and flooding, LID-combinations perform better than individual LID implementations. For the five return periods (one, five, 20, 50, and 100 years), the LID-combination reduced runoff by 67.83, 65.02, 50.44, 40.18, and 35.88%, and reduced flooding by 85.32, 72.65, 54.05, 46.17, and 42.80%, respectively. Additionally, the reduction rate of overflow junctions is 100, 100, 80, 67, and 70%, respectively.


Characterizing K2 Candidate Planetary Systems Orbiting Low-Mass Stars IV: Updated Properties for 86 Cool Dwarfs Observed During Campaigns 1-17.
We present revised stellar properties for 172 K2 target stars that were identified as possible hosts of transiting planets during Campaigns 1-17. Using medium-resolution near-infrared spectra acquired with the NASA Infrared Telescope Facility/SpeX and Palomar/TripleSpec, we found that 86 of our targets were bona fide cool dwarfs, 74 were hotter dwarfs, and 12 were giants. Combining our spectroscopic metallicities with Gaia parallaxes and archival photometry, we derived photometric stellar parameters and compared them to our spectroscopic estimates. Although our spectroscopic and photometric radius and temperature estimates are consistent, our photometric mass estimates are systematically ΔM * = 0.11 M⊙ (34%) higher than our spectroscopic mass estimates for the least massive stars (M *,phoi < 0.4 M⊙). Adopting the photometric parameters and comparing our results to parameters reported in the Ecliptic Plane Input Catalog, our revised stellar radii are ΔR * = 0.15R⊙ (40%) larger and our revised stellar effective temperatures are roughly ΔT eff = 65K cooler. Correctly determining the properties of K2 target stars is essential for characterizing any associated planet candidates, estimating the planet search sensitivity, and calculating planet occurrence rates. Even though Gaia parallaxes have increased the power of photometric surveys, spectroscopic characterization remains essential for determining stellar metallicities and investigating correlations between stellar metallicity and planetary properties.


Optical design of zero-power Hubble Space Telescope wave-front correctors for null testing.
The optical design of the second-generation wide-field/planetary-camera instrument for the Hubble Space Telescope has been modified to compensate for the spherical aberration of the optical telescope assembly (OTA) by introduction of undercorrected spherical aberration into the wave front. This instrument can be tested in a simple manner to ensure that its aberration contribution has the proper sign and magnitude. We present designs for a near-zero power doublet lens that can be used to generate a spherically aberrated wave front that is similar to the OTA wave front. When this lens is used in combination with the instrument, a near-perfect or nulled wave front should be produced, resulting in a high-quality point image on axis. We also present lens designs for a similar test that can be performed on the OTA simulators now being built to verify the other second-generation instruments.


H4K5 histone acetylation of BRG1 is associated with heroin administration rather than addiction.
Diacetylmorphine hydrochloride (heroin) addiction is a chronic relapsing brain disorder that is a heavy public health burden worldwide. Brm/SWI2-related gene-1 (BRG1) is a tumor suppressor gene that can influence embryogenesis and the development of the cerebellum. The current study aimed to investigate the effect of histone H4 lysine 5 (H4K5) modifications on the BRG1 gene in brain tissue of the ventral tegmental area (VTA) of heroin-addicted rats. A total of 21 male Sprague Dawley rats were raised in a standard manner and underwent heroin self-administration training. Rats were randomly divided into three equal groups: Group A, self-administered delivery of heroin; group B, yoked delivery of heroin; and group C, yoked delivery of saline. The VTA was harvested and subjected to chromatin immunoprecipitation (ChIP) analysis. Gene expression was evaluated by quantitative polymerase chain reaction. We calculated the recovery rate, which indicated the percentage of the total input BRG1 recovered by ChIP. Our results showed that BRG1 was less associated with H4K5 histone modification in the group of rats that underwent heroin self-administration than in the other two groups (A vs. B, P=0.031; A vs. C, P=0.067). The recovery fold changes of the self-administration group and the passive-administration group were significantly different from those of the group with yoked saline (A vs. C, P=0.013; B vs. C, P=0.009; A vs. B, P=0.731). The results of the current study demonstrated that H4K5 histone acetylation of BRG1 in the VTA may be associated with heroin administration, but not addiction.


Vasculitic Peripheral Neuropathy, Differences Between Systemic and Non-Systemic Etiologies: A Case Series and Biopsy Report.
Vasculitic peripheral neuropathy (VPN) is caused by vessel inflammation leading to peripheral nerve injury of acute-to-subacute onset. When VPN occurs in the context of systemic disease it is classified as Systemic Vasculitic Neuropathy (SVN) and as Non-Systemic Vasculitic Neuropathy (NSVN) when restricted to the nerves. This study aimed to compare the clinical characteristics, biopsy findings and disease outcome in patients with VPN. Clinical records of adult patients with VPN diagnosed at our institution between June-2002 and June-2019 were retrospectively reviewed. Demographic characteristics, clinical manifestations, nerve conduction studies, nerve biopsies, treatment and clinical evolution were analyzed in all patients with at least 6 months follow-up. Twenty-five patients with VPN were included (SVN, n = 10; NSVN, n = 15). No significant differences in demographic or clinical features were found between groups. The median delay between symptom onset and nerve biopsy was significantly longer in NSVN patients (10 vs 5.5 months, p = 0.009). Erythrocyte sedimentation rate (ESR) values over 20 mm/h were significantly more common in SVN patients (100% vs. 60%, p = 0.024). Nerve biopsies showed active lesions more frequently in treatment-naive patients compared to those who had received at least 2 weeks of corticosteroids (92% vs 38%; p = 0.03), with a higher proportion of definite VPN cases (92 vs 46%; p = 0.04). Although the clinical manifestations are similar, ESR is an important tool to help distinguish between both conditions. Early nerve biopsy in untreated patients increases diagnostic accuracy, avoiding misdiagnosis.


Estimation and false discovery control for the analysis of environmental mixtures.
The analysis of environmental mixtures is of growing importance in environmental epidemiology, and one of the key goals in such analyses is to identify exposures and their interactions that are associated with adverse health outcomes. Typical approaches utilize flexible regression models combined with variable selection to identify important exposures and estimate a potentially nonlinear relationship with the outcome of interest. Despite this surge in interest, no approaches to date can identify exposures and interactions while controlling any form of error rates with respect to exposure selection. We propose two novel approaches to estimating the health effects of environmental mixtures that simultaneously (i) estimate and provide valid inference for the overall mixture effect and (ii) identify important exposures and interactions while controlling the false discovery rate (FDR). We show that this can lead to substantial power gains to detect weak effects of environmental exposures. We apply our approaches to a study of persistent organic pollutants and find that controlling the FDR leads to substantially different conclusions.


Investigating the effect of aqueous extracts of basil and savory on antioxidant activity, microbial and sensory properties of probiotic yogurt.
The low viability of probiotics causes the short shelf life of fermented products. Therefore compounds which prolong the viability of probiotic bacteria can increase or at least maintain the health- benefiting properties of these products. On the other hand, the addition of antioxidants is one of the methods to increase the shelf life of food products which has recently become more prevalent. In this respect, herbal extracts which are a good source of antioxidants can be appropriate alternative. The aim of this study was to evaluate the effect of adding basil and savory extracts on antioxidant activity, and on the microbial and organoleptic characteristics of probiotic yogurt. The effect of adding basil extract (8% and 10%) and savory extract (6% and 8%) separately to low fat yogurt (1.5% fat) containing Lactobacillus paracasei subsp. paracasei was investigated. The samples were stored at 4°C. The viability of Lactobacillus paracasei subsp. paracasei, antioxidant activ- ity and sensory properties of probiotic yogurt were evaluated on the 1st, 7th, 14th and 21st days. Basil and savory extracts significantly increased the viability of probiotic bacteria (p < 0.05). Dur- ing storage, probiotic counts markedly decreased (p < 0.05) in comparison to the control sample. The addi- tion of herbal extracts significantly increased antioxidant activity, but this activity decreased during storage (p < 0.05). The scores for taste, odor, color and overall acceptance decreased as herbal extracts increased, but there was no significant difference between the test samples and control sample in terms of the texture score (p > 0.05). During storage, there was no significant difference between the organoleptic scores of the samples (p > 0.05), but the taste score did increase significantly (p < 0.05). It can be concluded that adding herbal extracts had a positive effect on the viability of probiotics and antioxidant activity of probiotic yogurt.


Involvement of nitric oxide in neuroglycopenia-induced insulin and glucagon secretion in the mouse.
Neuroglycopenia induced by administration of 2-deoxy-D-glucose is known to stimulate the secretion of both insulin and glucagon in mice by a mechanism that is dependent on neural activity. In the present study, we examined whether the neurotransmitter nitric oxide (NO) is involved in this process. Therefore, 2-deoxy-D-glucose (500 mg/kg) was injected intravenously alone or together with the inhibitor of NO synthase, NG-nitro-L-arginine methyl ester (50 mg/kg) to conscious mice. It was found that NG-nitro-L-arginine methyl ester inhibited the increased plasma levels of both insulin (by 26%; P = 0.039) and glucagon (by 45%; P < 0.001) at 10 min after injection of 2-deoxy-D-glucose. Similarly, the NO synthase inhibitor, NG-nitro-L-arginine, which is devoid of the anticholinergic property of NG-nitro-L-arginine methyl ester, inhibited the responses of both insulin (by 53%; P = 0.026) and glucagon (by 57%; P = 0.003) to 2-deoxy-D-glucose. In contrast, the stereoisomer of NG-nitro-L-arginine methyl ester, NG-nitro-D-arginine methyl ester, which is devoid of NO synthase inhibitory activity, was without effect on 2-deoxy-D-glucose-induced insulin and glucagon secretion. Plasma levels of adrenaline and noradrenaline after administration of 2-deoxy-D-glucose were also reduced by NG-nitro-L-arginine methyl ester. In contrast, the insulin and glucagon secretory responses to intravenous injection of arginine (250 mg/kg), glucose (500 mg/kg) or the cholinergic agonist, carbachol (30 micrograms/kg), were not influenced by NG-nitro-L-arginine methyl ester, NG-nitro-D-arginine methyl ester or NG-nitro-L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)


View dependencies in the visual recognition of social interactions.
Recognizing social interactions, e.g., two people shaking hands, is important for obtaining information about other people and the surrounding social environment. Despite the visual complexity of social interactions, humans have often little difficulties to visually recognize social interactions. What is the visual representation of social interactions and the bodily visual cues that promote this remarkable human ability? Viewpoint dependent representations are considered to be at the heart of the visual recognition of many visual stimuli including objects (Bülthoff and Edelman, 1992), and biological motion patterns (Verfaillie, 1993). Here we addressed the question whether complex social actions acted out between pairs of people, e.g., hugging, are also represented in a similar manner. To this end, we created 3-D models from motion captured actions acted out by two people, e.g., hugging. These 3-D models allowed to present the same action from different viewpoints. Participants' task was to discriminate a target action from distractor actions using a one-interval-forced-choice (1IFC) task. We measured participants' recognition performance in terms of reaction times (RT) and d-prime (d'). For each tested action we found one view that led to superior recognition performance compared to other views. This finding demonstrates view-dependent effects of visual recognition, which are in line with the idea of a view-dependent representation of social interactions. Subsequently, we examined the degree to which velocities of joints are able to predict the recognition performance of social interactions in order to determine candidate visual cues underlying the recognition of social interactions. We found that the velocities of the arms, both feet, and hips correlated with recognition performance.


Awake craniotomy for glioma resection: Technical aspects and initial results in a single institution.
Although variations in the technique of awake craniotomy (AC) have been widely reported, a key member of this interdisciplinary procedure is the healthcare professional performing assessments of neurological function during resection. The expertise of the latter will depend on the neurological function to be tested and on available resources of the institution. This report details our initial experience of an AC service utilizing the expertise of a speech and language therapist (SLT) and an experienced neuro-physiotherapist (NP) to monitor patient function during glioma resection. Forty-five patients underwent 50 AC procedures for eloquently located gliomas over a 3-year period. Patients with a glioma involving speech or sensorimotor areas were assessed preoperatively by the SLT/NP respectively. The same therapist monitored the patient's neurological function intraoperatively and executed a rehabilitation program tailored to the needs of the patient in the postoperative period. Three patients underwent biopsy only, due to intraoperative seizures precluding intraoperative mapping (2 cases) or speech arrest on stimulation of a small recurrent tumor. The remaining 47 cases were suitable for repetitive neurological assessment "awake" during tumor debulking. One patient with a large sensorimotor tumor developed intraoperative hemiparesis due to outward brain herniation (which recovered postoperatively). Ten patients developed a new or worsened neurological deficit in the initial postoperative period (6 were detected intraoperatively), of which 5 eventually had resolution and returned to baseline function within 2 weeks. In our initial experience based anecdotally on a previous similar "non-awake" caseload, we have found AC with the input of the SLT/NP to be a key component in ensuring optimal functional outcomes for patients with gliomas in eloquently located areas.


Finite Class Bayesian Inference System for Circle and Linear Walking Gait Event Recognition Using Inertial Measurement Units.
Accurate and fast human motion pattern recognition is the key to ensuring lower limb assistive devices' appropriate assistance. The research on human motion pattern recognition of lower limb assistive devices mainly focuses on sagittal gait. The motion pattern such as circular walking (CW) is asymmetric about the sagittal plane of the body. CW is common in daily living. However, the recognition algorithm of CW is rarely reported. Since lower limb assistive devices interact with humans, lacking the capability of recognizing CW is dangerous. Thus, to realize the accurate and fast recognition of CW, this article proposed a finite class Bayesian interference system (FC-BesIS). FC-BesIS is designed to recognize walking activities (linear walking and CW) and gait events (heel contact, load response, mid stance, terminal stance, pre-swing, initial swing, mid swing, and terminal swing). A finite class method which reduces the number of potential classes according to elimination rules before decision-making is introduced. Elimination rules are designed based on likelihood estimation and sensor information. The experiments show that walking activities and gait events can be accurately and fastly recognized by FC-BesIS. The experiments also show that the performance of FC-BesIS in mean recognition accuracy (MRA) and mean decision time (MDT) is improved compared with BesIS. The MRA of walking activities and gait events are 100% and 97.38%, respectively. The MDT of walking activities and gait events are 28.19 ms and 33.94 ms, respectively. Overall, FC-BesIS has been proved to be an accurate and fast recognition algorithm for human motion patterns using wearable sensors.


A bio-inspired self-propelling endoscopic device for inspecting the large intestine.
This article presents an inchworm-inspired, pneumatic, endoscopic device intended to navigate inside a colon. The device consists of a propulsion segment with two linear balloons and two gripper segments with four twisted balloons. The three segments can be sequentially actuated by pressurized air, which achieves a propulsive motion like an inchworm. Experimental results of the pneumatic characteristics show that the device has excellent adaptability to pipes of different diameters and good controllability of the propulsion velocity. The device is flexible enough to pass through an elbow pipe without requiring special controls, and the inspection performance of a device equipped with a camera in a flexible pipe is also presented. Moreover, the device is able to advance in an excised swine colon, which shows its great potential for applications in colonoscopy.


Thermal Degradation of Polystyrene (PS) Nanocomposites Loaded with Sol Gel-Synthesized ZnO Nanorods.
Thermal degradation of polystyrene/ZnO (PS/ZnO) nanocomposites was investigated in this study. PS/ZnO polymer nanocomposites were prepared by using ZnO nanorods as nanofillers that were prepared via the sol-gel route. The as-prepared ZnO nanoparticles showed nanocrystallites in rod-like shapes with a non-uniform hexagonal cross-section and diameter varying from 40 to 75 nm. PS/ZnO nanocomposites with ZnO nanoparticles content ranging from 0-3 wt% are prepared via the common casting method. Even dispersion for ZnO nanoparticles within as-prepared PS/ZnO nanocomposites was verified through SEM/EDX measurements. Thermal degradation of the samples was checked by using the thermogravimetric (TG) analysis and differential scanning calorimetry (DSC) under non-isothermal conditions and a constant heating rate of 10 °C min. The thermal stability of the nanocomposite is elevated compared to that of pristine PS due to the addition of the ZnO nanoparticles. The homogeneity of the PS/ZnO nanocomposites is verified by systematic increases in thermal degradation with increasing ZnO content. The characterization degradation temperatures at different weight loss percentages of ZnO nanoparticles increase at high ZnO wt%. Static activation energy of decomposing is based on TGA data. Activation energies showed some enhancement after the addition of ZnO nanorods into the PS matrix. Enhancing the thermal stability of PS with ZnO addition within the investigated ZnO concentration range is verified by TG, DSC results.


Demonstrating the impact of your teaching: benefits of Higher Education Academy Fellowship for librarians.
This feature suggests that health librarians who teach or support Higher Education (HE) students can and should gain accreditation and recognition for their teaching by the route of HEA Fellowship. We outline the process by which Fellowship could be attained by those working within HE and those in NHS libraries who work with HE students, suggesting which aspects of librarianship practice could provide the necessary evidence for Fellowship. The synergies between Fellowship and Chartership are examined and the criteria for HEA (UK Professional Standards Framework or UKPSF) are mapped against those for Chartership (Professional Knowledge and Skills Base (PKSB). D.I.


Neoplasias of the colorectal crypts.
Colorectal cancers are often preceded by noninvasive neoplasias arising in the surface epithelium, namely tubular, tubulovillous and villous adenomas. That neoplasias may also arise in the colorectal crypts is less well known. Between 1998 and 2002, colonoscopies, rectoscopies and colorectal surgical specimens from 8647 patients were received at this Department for histological diagnosis. The material included 502 adenomas, 865 invasive tumours and 221 cases of ulcerative colitis (UC). The following cryptal lesions were investigated: (a) neoplasias arising in the crypts, (b) neoplasias possibly arising in the crypts and (c) cryptal lesions alleged to be premalignant. Over the 5-year period, the most frequent phenotype encountered was single crypt dysplasia (in all 5 colectomies from familial adenomatous polyposis patients), followed by serrated adenomas (11.2%), hyperplastic polyps (8.4%), dysplasia in UC (6.3%), pure carcinoid tumours (1.7%), signet ring cell carcinoma (1.1%), adenocarcinoid tumours (0.2%) and de novo carcinomas (0.1%). In this survey, no case of Paneth cell adenoma or of cryptal neoplasia in lymphoid-associated mucosa (also known to originate from the crypts) was found. Hence, it was demonstrated that several neoplasia phenotypes actually arise in the colorectal crypts. The awareness that colorectal neoplasias may evolve from that particular cellular domain may cast more light on the understanding of the complex mechanisms of colorectal carcinogenesis.


Religiosity and adolescents' premarital sexual attitudes and behaviour: an empirical study of conceptual issues.
A review of the literature concerning the relationship between religiosity and premarital sexual attitudes and behavior revealed inconsistencies in research findings and problems with methodology and operationalization of variables. A postal questionnaire to 527 16-18 year olds examined the associations between 6 models of religiosity (religious upbringing, denominational affiliation, ritual/behavioral, self-attitude/self-schema, and salience of religious identity) and personal sexual standards, attitudes towards sexually active others, virginal status, anticipation of sexual intercourse, and frequency of both coitus and noncoital sexual experiences over the previous year. A negative relationship between religiosity and a number of sexual attitudes and behaviors was observed, though nonsignificant relationships in the case of sexual experiences without intercourse suggested the maintenance of a technical virginity to accord with religious precepts. There was also some evidence that Catholic adolescents were more likely to be sexually active than non-Catholics when current religiosity was controlled for. The results lent strongest support to models which implicated self-conception either in terms of self-attitudes/self-schemas or the salience of religious identity. Implications of the study and suggestions for future research are outlined.


A Novel Robotic-Assisted Technique to Implant the Responsive Neurostimulation System.
The responsive neurostimulation system (RNS) (NeuroPace Inc, Mountain View, California) was approved as an adjunctive therapy for medically refractory focal epilepsy. RNS detects epileptiform patterns and delivers electrical stimulation to abort seizures. To describe a novel technique of RNS lead implantation using robotic-assisted targeting of ictal-onset zones based on stereoelectroencephalography (sEEG) localization. Secondary objectives are to report the accuracy of robotic-assisted lead implantation using the ROSA robot as well as to report the clinical outcome achieved after RNS implantation by this method. A total of 16 patients with medically refractory focal epilepsy underwent sEEG implantation for ictal-onset localization followed by robotic RNS implantation. The electrode most correlative with ictal onset on sEEG was chosen as the target for the RNS electrode. Seizure control was measured at 6-mo and 1-yr follow-up. Ictal-onset electrocorticography (ECoG) data from RNS were compared with ictal onset from sEEG leads based on calculations of lead target to actual lead location from the ROSA robot. At 6-mo follow-up, the average percent seizure reduction was 82% based upon self-reported seizure diaries. At 1-yr follow-up, 8 patients had an average of 90% seizure reduction. The location of seizure onset from ECoG data show similar onset from sEEG leads within 0.165-mm discrepancy. The ROSA robot provides an ideal method for targeting subcortical ictal-onset zones. This method of RNS lead implantation achieves high accuracy and is associated with favorable clinical outcomes.


Development of Multifunctional Pullulan/Chitosan-Based Composite Films Reinforced with ZnO Nanoparticles and Propolis for Meat Packaging Applications.
Pullulan/chitosan-based multifunctional edible composite films were fabricated by reinforcing mushroom-mediated zinc oxide nanoparticles (ZnONPs) and propolis. The ZnONPs were synthesized using enoki mushroom extract and characterized using physicochemical methods. The mushroom-mediated ZnONPs showed an irregular shape with an average size of 26.7 ± 8.9 nm. The combined incorporation of ZnONPs and propolis pointedly improved the composite film's UV-blocking property without losing transparency. The reinforcement with ZnONPs and propolis improved the mechanical strength of the pullulan/chitosan-based film by ~25%. Additionally, the water vapor barrier property and hydrophobicity of the film were slightly increased. In addition, the pullulan/chitosan-based biocomposite film exhibited good antioxidant activity due to the propolis and excellent antibacterial activity against foodborne pathogens due to the ZnONPs. The developed edible pullulan/chitosan-based film was used for pork belly packaging, and the peroxide value and total number of aerobic microorganisms were significantly reduced in meat wrapped with the pullulan/chitosan/ZnONPs/propolis film.


Hybrid stage I palliation in a 1.1 kg, 28-week preterm neonate with posterior malalignment ventricular septal defect, left ventricular outflow tract obstruction, and coarctation of the aorta.
The hybrid stage I procedure has emerged as a less-invasive alternative to the standard surgical Norwood procedure in the palliation of high-risk hypoplastic left heart syndrome and variants. This approach may also benefit patients requiring complex neonatal repair who have significant anatomic and/or perioperative risk factors that either prevent or complicate durable and robust biventricular circulation from being safely achieved. An extremely low-birth weight (1.1 kg) 28-week gestation preterm neonate with postnatal diagnosis of posterior malalignment ventricular septal defect, severe left ventricular outflow tract obstruction, aortic annular hypoplasia, and aortic arch obstruction underwent initial palliation with a hybrid stage I procedure. In this case, hybrid stage I palliation allowed for both somatic and left heart growth followed by ultimate uncomplicated biventricular repair.


Green approaches for the synthesis of metal and metal oxide nanoparticles using microbial and plant extracts.
Green synthesis approaches are gaining significance as promising routes for the sustainable preparation of nanoparticles, offering reduced toxicity towards living organisms and the environment. Nanomaterials produced by green synthesis approaches can offer additional benefits, including reduced energy inputs and lower production costs than traditional synthesis, which bodes well for commercial-scale production. The biomolecules and phytochemicals extracted from microbes and plants, respectively, are active compounds that function as reducing and stabilizing agents for the green synthesis of nanoparticles. Microorganisms, such as bacteria, yeasts, fungi, and algae, have been used in nanomaterials' biological synthesis for some time. Furthermore, the use of plants or plant extracts for metal and metal-based hybrid nanoparticle synthesis represents a novel green synthesis approach that has attracted significant research interest. This review discusses various biosynthesis approaches via microbes and plants for the green preparation of metal and metal oxide nanoparticles and provides insights into the molecular aspects of the synthesis mechanisms and biomedical applications. The use of agriculture waste as a potential bioresource for nanoparticle synthesis and biomedical applications of biosynthesized nanoparticles is also discussed.


Ultrasensitive Pressure-Induced Optical Materials: Europium-Doped Hafnium Silicates with a Khibinskite Structure for Optical Pressure Sensors and WLEDs.
Ultrasensitive pressure-induced optical materials are of great importance owing to their potential applications in optical pressure sensors. However, the lack of outstanding pressure sensitivity, observable color evolution, and structure reliability limits their further development in both practical applications and luminescence theory. To overcome the above problems, an enlightening methodology is proposed to explore the high sensitivity and phase stability of hafnium silicate K2HfSi2O7 (KHSO) phosphor with a Khibinskite structure. By employing X-ray diffraction (XRD) Rietveld refinement, cryogenic spectroscopy, and ancillary calculations, information on Eu2+ ion occupation is completely obtained at atmospheric pressure. The remarkable pressure sensitivity (dλ/dP = 3.25 nm/GPa-1) and excellent phase stability up to 20 GPa, along with the reproducible color hue variation, exhibit unprecedented superiority when used in optical pressure sensors. These advantages can be assigned to the pressure-induced Eu2+-selective occupation and the unique properties of 5d-4f transition (Stokes shift, nephelauxetic effect, and intense crystal field strength), which are clearly proved by measuring the XRD patterns, Raman spectra, and Gaussian fitting spectra under compression and decompression processes. The excellent luminescence property manifests that KHSO/Eu2+ can be considered as a potential luminescent material for solid-state lighting and optical pressure sensors.


Antagonistic effects of high and low temperature pretreatments on the germination and pregermination ethylene synthesis of lettuce seeds.
Red light-induced germination of Grand Rapids lettuce seeds (Lactuca sativa L.) incubated at 20 C was inhibited if the seeds were first imbibed at 30 C for 36 hours. This effect was counteracted by exogenous ethylene and associated with a reduction in the rate at which the seeds produced ethylene throughout the pregermination period. A chilling treatment reversed the effect of a prior imbibition at 30 C on both germination and ethylene production. The possibility that the pretreatments influence germination through their effects on ethylene production is discussed.Other evidence presented indicates that the inability of seeds to germinate at supraoptimal temperature is not due either to a rapid loss of far red-absorbing phytochrome or to an inadequate capacity for ethylene synthesis. It was also shown that a chilling treatment potentiated germination at high temperature without affecting the ethylene synthetic capacity of the seeds.


Expression and localization of calreticulin in tobacco anthers and pollen tubes.
The developmental expression pattern and localization of calreticulin were studied in Nicotiana tabacum L. anthers, pollen and pollen tubes. High transcript and protein levels were detected throughout anther development. Immunolocalization of calreticulin in the anthers showed particular dense label in tapetum and pollen at developmental stage 2, when the tapetum is highly active and the pollen tetrads are formed. Much lower transcript and protein levels were detected in dry and hydrated pollen and in pollen tubes. Immunofluorescence labeling of both chemically fixed and cryo-fixed and freeze-substituted pollen tubes showed the presence of calreticulin in Golgi apparatus and endoplasmic reticulum (ER). Calreticulin was seen throughout the stacks in the Golgi apparatus and in the areas with coated-Golgi vesicles but much less so in the ER. Calreticulin was not found in the secretory vesicles. A relatively intense label was occasionally seen adjacent to the wall of the tube. No significant label was observed in mitochondria, vacuoles, generative cells, cell wall or callose plugs. The present results are consistent with a role of calreticulin in Ca2+-dependent folding of secreted glycoproteins in tapetum, pollen and pollen tubes.


Nerve growth factor enhances the excitability of rat sensory neurons through activation of the atypical protein kinase C isoform, PKMζ.
Our previous work showed that nerve growth factor (NGF) increased the excitability of small-diameter capsaicin-sensitive sensory neurons by activating the p75 neurotrophin receptor and releasing sphingolipid-derived second messengers. Whole cell patch-clamp recordings were used to establish the signaling pathways whereby NGF augments action potential (AP) firing (i.e., sensitization). Inhibition of MEK1/2 (PD-98059), PLC (U-73122, neomycin), or conventional/novel isoforms of PKC (bisindolylmaleimide I) had no effect on the sensitization produced by NGF. Pretreatment with a membrane-permeable, myristoylated pseudosubstrate inhibitor of atypical PKCs (aPKCs: PKMζ, PKCζ, and PKCλ/ι) blocked the NGF-induced increase in AP firing. Inhibitors of phosphatidylinositol 3-kinase (PI3K) also blocked the sensitization produced by NGF. Isolated sensory neurons were also treated with small interfering RNA (siRNA) targeted to PKCζ. Both Western blots and quantitative real-time PCR established that PKMζ, but neither full-length PKCζ nor PKCλ/ι, was significantly reduced after siRNA exposure. Treatment with these labeled siRNA prevented the NGF-induced enhancement of excitability. Furthermore, consistent with the high degree of catalytic homology for aPKCs, internal perfusion with active recombinant PKCζ or PKCι augmented excitability, recapitulating the sensitization produced by NGF. Internal perfusion with recombinant PKCζ suppressed the total potassium current and enhanced the tetrodotoxin-resistant sodium current. Pretreatment with the myristoylated pseudosubstrate inhibitor blocked the increased excitability produced by ceramide or internal perfusion with recombinant PKCζ. These results demonstrate that NGF leads to the activation of PKMζ that ultimately enhances the capacity of small-diameter capsaicin-sensitive sensory neurons to fire APs through a PI3K-dependent signaling cascade.


Regional and cellular pathology in frontotemporal dementia: relationship to stage of disease in cases with and without Pick bodies.
Frontotemporal dementia (FTD) is a prevalent neurodegenerative disease of heterogeneous histopathology. Neuropathological subtypes are identified on the basis of the presence or absence of tau- or ubiquitin-positive neuronal inclusions. Our recent work has established four disease stages that are independent of neuropathological subtype and reflect the clinical and degenerative progression observed in FTD. The variability in the extent of neuronal loss, astrogliosis, and microvacuolation are, therefore, more likely to reflect disease stage with potentially predictable differences between cases at early versus late disease stages. Understanding the variability in these parameters may assist in determining the importance of diverse disease subtypes in FTD. We examined 21 cases of sporadic, behavioural variant FTD and quantified the progression of histopathological change. The neuropathology of early disease was marked by severe astrogliosis of both the frontal and temporal cortices and neuronal loss, which was more evident in upper cortical layers of the frontal lobe. In late disease, neuronal loss was evident from both layer III and V in frontal and temporal cortices, and particularly the CA1 sector of the hippocampus. In addition, we compared the neuropathology of Pick's disease, dementia lacking distinctive histopathology and FTD with motor neuron disease, and found no difference in these pathological subtypes on the basis of neuronal loss, astrogliosis or microvacuolation. These results show that the earliest cellular changes in FTD occur in glia, and that disease stage rather than FTD subtype determines the pattern and extent of neuronal degeneration.


T cell receptor (TCR)-induced death of immature CD4+CD8+ thymocytes by two distinct mechanisms differing in their requirement for CD28 costimulation: implications for negative selection in the thymus.
Negative selection is the process by which the developing lymphocyte receptor repertoire rids itself of autoreactive specificities. One mechanism of negative selection in developing T cells is the induction of apoptosis in immature CD4+CD8+ (DP) thymocytes, referred to as clonal deletion. Clonal deletion is necessarily T cell receptor (TCR) specific, but TCR signals alone are not lethal to purified DP thymocytes. Here, we identify two distinct mechanisms by which TCR-specific death of DP thymocytes can be induced. One mechanism requires simultaneous TCR and costimulatory signals initiated by CD28. The other mechanism is initiated by TCR signals in the absence of simultaneous costimulatory signals and is mediated by subsequent interaction with antigen-presenting cells. We propose that these mechanisms represent two distinct clonal deletion strategies that are differentially implemented during development depending on whether immature thymocytes encounter antigen in the thymic cortex or thymic medulla.


Ulcer healing potential of ethanolic extract of Caralluma attenuata on experimental diabetic rats.
Available data indicated that diabetes mellitus (DM) increases the vulnerability of the gastric ulcers and the need of the hour is to develop effective agents to treat ulcer with diabetes for better patient compliance and cost effectiveness. The ulcer-healing properties of ethanolic extract of Caralluma attenuata (CAEt) against both chemically- and physically induced gastric ulcers in experimental rats are recently studied. To assess the ulcer healing potential of Ethanolic Extract of Caralluma attenuata on Experimental Diabetic Rats. The current study aimed to evaluate ulcer healing properties of CAEt on the aspirin induced gastric ulcer in rats with streptozotocin induced DM. The hypothesis is based on the fact that DM results in compromising the mucosal defensive factors associated with delay in gastric ulcer healing, and if these changes can be corrected by using agents known for their antidiabetic and antiulcer properties. Experimental albino rats were divided into six groups. Except for Group I, other groups contained streptozotocin-induced diabetic rats. Group I (normal control) and Group II (diabetic control) were administered vehicle, Groups III and IV (diabetic experimental) were administered CAEt in dose of 100 mg/kg and 250 mg/kg, respectively, and Groups V and VI (positive controls) were respectively administered oral standard drugs omeprazole, 20 mg/kg, and tolbutamide 10 mg/kg. The results confirmed that the CAEt significantly decreases the ulcer index (P < 0.05) in the aspirin-induced gastric ulcers and also significantly exhibit antioxidant and glucose lowering activity in the diabetic ulcer rats. The study showed that C. attenuata has the potential to be used as an antiulcer agent in experimental diabetic rats.


Fusion of the erythropoietin receptor and the Friend spleen focus-forming virus gp55 glycoprotein transforms a factor-dependent hematopoietic cell line.
The Friend spleen focus-forming virus (SFFV) gp55 glycoprotein binds to the erythropoietin receptor (EPO-R), causing constitutive receptor signaling and the first stage of Friend erythroleukemia. We have used three independent strategies to further define this transforming molecular interaction. First, using a retroviral selection strategy, we have isolated the cDNAs encoding three fusion polypeptides containing regions of both EPO-R and gp55. These fusion proteins, like full-length gp55, transformed the Ba/F3 factor-dependent hematopoietic cell line and localized the transforming activity of gp55 to its transmembrane domain. Second, we have isolated a mutant of gp55 (F-gp55-M1) which binds, but fails to activate, EPO-R. We have compared the transforming activity of this gp55 mutant with the EPO-R-gp55 fusion proteins and with other variants of gp55, including wild-type polycythemia Friend gp55 and Rauscher gp55. All of the fusion polypeptides and mutant gp55 polypeptides were expressed at comparable levels, and all coimmunoprecipitated with wild-type EPO-R, but only the Friend gp55 and the EPO-R-gp55 fusion proteins constitutively activated wild-type EPO-R. Third, we have examined the specificity of the EPO-R-gp55 interaction by comparing the differential activation of murine and human EPO-R by gp55. Wild-type gp55 had a highly specific interaction with murine EPO-R; gp55 bound, but did not activate, human EPO-R.


Exchangeable sodium induced changes in yield, water relation and cation composition of fennel (Foeniculum vulgare Mill).
A pot experiment was conducted with the objectives to assess the adaptation potential of fennel crop grown at 10, 20, 25, 35 and 40 ESP (exchangeable sodium percentage) levels. Results showed that the rate of seed germination, plant growth including branching pattern, umbels per plant and 1000 test seed weight were adversely affected by sodic soils. Assuming that fifty percent reduction in seed yield and Na+/K+ ratio in leaf tissue as an index of alkali tolerance revealed that fennel was tolerant up to 25 ESP. The cell sap pH and EC reflected optimum osmoticum maintenance to withstand sodicity stress at this level and beyond this leaf water potential decreased (negatively) more to impede water uptake.


Activity levels of some radionuclides in Mariout and Brullus lakes, Egypt.
Mariout and Brullus are two of the highly fish-productive lakes in the northern coast of Egypt along the Mediterranean Sea. They are widely used to drain industrial wastes, sewage and agriculture drainage. The activities of (238)U, (232)Th, (40)K and (137)Cs were measured in the uppermost part of the surface sediments of the two lakes, using gamma-ray spectrophotometry. Brullus Lake recorded significantly higher (238)U and (232)Th and lower (40)K (17.22±2.49, 10.03±0.56 and 299.70±17.78 Bq kg(-1)) than Mariout Lake (12.65±1.53, 7.24±0.76 and 518.75±46.24 Bq kg(-1), respectively). Cesium-137 shows nearly equal activities in both lakes (3.33±0.46 and 3.68±0.70 Bq kg(-1), respectively). Activity distributions of (238)U and (232)Th in the sediments of Mariout Lake show a significant increase to the west, southwest and northeast, (40)K activity increased westwards, while the (137)Cs level was increased to the east and northeast, indicating agriculture drainage, industrial wastes and lands reclamation around the lake. At Brullus Lake, the activity trends of (238)U, (232)Th, (40)K and(137)Cs were increasing to the west and south towards the agriculture and industrial waste-water-feeding drains.


Endothelin receptor antagonism: role in the treatment of pulmonary arterial hypertension related to scleroderma.
Pulmonary arterial hypertension (PAH) is a devastating disease, which is associated with a 1-year survival of about 50% without specific treatment. Pulmonary vascular remodelling, thrombosis and vasoconstriction are thought to be directly involved in increasing pulmonary vascular resistance (PVR), which, left untreated, ultimately leads to right ventricular failure and death. A total of 10-12% of patients with systemic sclerosis (SSc) develop PAH, which is a leading cause of mortality in these patients. Targeted treatment regimens involving oral therapies, in particular endothelin receptor antagonists (ERAs), such as bosentan, sitaxsentan (sitaxentan) and ambrisentan, are now being used and this approach has improved symptoms as well as survival. 1-Year survival has improved to about 80%, while 3-year survival in advanced SSc-PAH has improved from 44% to 65% since the introduction of ERAs. Subanalysis of BREATHE-1, a pilot study and the STRIDE-2X randomized controlled trials has reported improvements in time to clinical worsening, 6-minute walk distance (6mwd) and right heart haemodynamics in SSc-PAH patients given bosentan and sitaxsentan, respectively, compared with placebo. The ARIES studies have also demonstrated a delay in the time to clinical worsening and improvement in 6mwd in connective tissue associated-PAH patients given ambrisentan compared with placebo. Unfortunately, these drugs are expensive and also have the potential for adverse interactions with other PAH and supportive therapies. Mandatory monthly liver function tests are required for safe administration of bosentan, ambrisentan and sitaxsentan, while dose adjustment of warfarin and careful monitoring are required when sitaxsentan is initiated. Earlier diagnosis and treatment of PAH may further improve outcomes with current ERAs. WHO functional class (FC) has traditionally been used to determine which patients with PAH will start therapy. The EARLY study has reported significant reductions in PVR and time to clinical worsening in mildly symptomatic PAH patients treated with bosentan, and many PAH clinicians now believe WHO FC should be used as a monitoring tool once targeted therapies have been initiated and not as a tool for deciding when to start PAH specific therapies.Many pathways are thought to be involved in the pathophysiology of the PAH. There is growing evidence that combination therapies targeting different pathophysiological steps may be necessary to effectively treat SSc-PAH. The COMPASS-1 study has reported an acute haemodynamic benefit in PAH when a single-dose of sildenafil is used in combination with bosentan and COMPASS-2 will investigate whether this acute response translates into long-term benefit. Well designed morbidity and mortality trials in SSc-PAH should help increase our understanding and treatment of this orphan disease.


Autonomic nervous function and baroreflex sensitivity in hypertensive diabetic patients.
Little is known about how the cardiac autonomic nervous function (CAN) changes with gradually increasing systolic blood pressure (SBP). This study investigated cardiac autonomic nervous function in diabetic patients and controls with different grades of SBP. We measured heart rate variability (HRV) and spontaneous baroreflex sensitivity (BRS) by power spectral analysis in 118 Chinese type-2 diabetic patients and 137 age-matched controls. Subjects were further subdivided into 4 SBP groups. Results showed total HRV and BRS values were significantly lower in several diabetic SBP groups. Total HRV and BRS decreased with increasing SBP, with significant differences in the 140-159 mm Hg or 160-179 mm Hg groups compared with other groups of diabetic and control subjects. We found that HRV and BRS can reflect cardiovascular autonomic dysfunction of diabetes when accompanied by hypertension. In our selected Chinese diabetic and control subjects, HRV and BRS parameters were influenced by gradually increasing SBP.


Cardiac vagal effects of rilmenidine in the dog: comparison with clonidine.
1. The cardiac vagal effects of rilmenidine (5 micrograms kg-1 min-1) and clonidine (0.5 micrograms kg-1 min-1) were studied in chloralose anaesthetized dogs. 2. Rilmenidine and clonidine progressively reduced the vagal stimulation-induced bradycardia. As indicated by the ED70, rilmenidine was about 23 times less potent than clonidine in this respect. Concomitantly, both drugs dose-relatedly decreased heart rate and mean blood pressure with potency ratios of rilmenidne to clonidine of about 1:23 and 1:12, respectively. 3. Importantly, the heart rate values observed under vagal stimulation during drug infusion never exceeded the values under basal vagal stimulation, and with both drugs large interindividual variations occurred under vagal stimulation. 4. These results show that the vagal bradycardia inhibition produced by rilmenidine and clonidine results from their true bradycardic effects and not from actual cardiac vagolytic properties.


A correlation between Magnetic Resonance Spectroscopy (1-H MRS) and the neurodevelopment of two-year-olds born preterm in an EPIRMEX cohort study.
Preterm infants are at risk of neurodevelopmental impairments. At present, proton magnetic resonance spectroscopy (1H-MRS) is currently used to evaluate brain metabolites in asphyxiated term infants. The purpose of this study was to identify in the preterm EPIRMEX cohort any correlations between (1H-MRS) metabolites ratio at term equivalent age (TEA) and neurodevelopmental outcomes at 2 years. Our study included EPIRMEX eligible patients who were very preterm infants (gestational age at birth ≤32 weeks) and who underwent a brain MRI at TEA and 1H-MRS using a monovoxel technique. The volumes of interest (VOI) were periventricular white matter posterior area and basal ganglia. The ratio of N Acetyl Aspartate (NAA) to Cho (Choline), NAA to Cr (creatine), Cho to Cr, and Lac (Lactate) to Cr were measured. Neurodevelopment was assessed at 24 months TEA with ASQ (Ages and Stages Questionnaire). A total of 69 very preterm infants had a 1H-MRS at TEA. In white matter there was a significant correlation between a reduction in the NAA/Cho ratio and a total ASQ and/or abnormal communication score, and an increase in the Lac/Cr ratio and an abnormality of fine motor skills. In the gray nuclei there was a trend correlation between the reduction in the NAA/Cho ratio and sociability disorders; and the increase in the Lac/Cr ratio and an anomaly in problem-solving. Using NAA as a biomarker, the vulnerability of immature oligodendrocytes in preterm children at TEA was correlated to neurodevelopment at 2 years. Similarly, the presence of lactate at TEA was associated with abnormal neurodevelopment at 2 years in the preterm brain.


Delivering the payload. Bacterial pathogenesis.
A specialized protein secretion pathway is used by some Gram-negative bacterial pathogens for delivery of virulence factors directly into mammalian host cells. This pathway is parallel to, and probably evolved from, a system used for construction of the bacterial flagellum.


Health care logistics: who has the ball during disaster?
In contemporary organizations, a wide gamut of options is available for sustaining and supporting health care operations. When disaster strikes, despite having tenable plans for routine replenishment and operations, many organizations find themselves ill-prepared, ill-equipped, and without effective mechanisms in place to sustain operations during the immediate aftermath of a crisis. Health care operations can be abruptly halted due to the non-availability of supply. The purpose of this work is to add to a necessary, growing body of works related specifically to health care logistics preparedness and disaster mitigation. Logistics management is a specialized genre of expertise within the health care industry and is largely contributive to the success or failure of health care organizations. Logistics management requires extensive collaboration among multiple stakeholders-internal and external to an organization. Effective processes and procedures can be largely contributive to the success or failure of organizational operations. This article contributes to the closure of an obvious gap in professional and academic literature related to disaster health care logistics management and provides timely insight into a potential problem for leaders industry-wide. One critical aspect of disaster planning is regard for competent logistics management and the effective provision of necessary items when they are needed most. In many communities, there seems to be little evidence available regarding health care logistics involvement in disaster planning; at times, evidence of planning efforts perceptibly end at intra-organizational doors within facilities. Strategic planners are being continually reminded that health care organizations serve a principal role in emergency preparedness planning and must be prepared to fulfill the associated possibilities without notification. The concern is that not enough attention is being paid to repeated lessons being observed in disasters and emergency events.


U-shaped association between body mass index and the prevalence of wheeze and asthma, but not eczema or rhinoconjunctivitis: the ryukyus child health study.
Studies reporting on the association between obesity and allergies have mostly focused on asthma. Little is known about the relationship of obesity to other allergic diseases, and the information that is available has been inconsistent. We examined the association between body mass index (BMI) and the prevalence of wheeze, asthma, eczema, and rhinoconjunctivitis in Japanese schoolchildren. Study subjects were 24,399 children aged 6-15 years in Okinawa, Japan. Outcomes were based on diagnostic criteria from the International Study of Asthma and Allergies in Childhood. BMI was categorized into five groups; <5th, 5th to 35th, >35th to 65th, >65th to 95th, and >95th percentile groups. Adjustment was made for sex, age, region of residence, number of siblings, smoking in the household, physical activity, paternal and maternal history of allergic disorders, and paternal and maternal educational levels. The prevalence values of wheeze, asthma, eczema, and rhinoconjunctivitis in the previous 12 months were 10.8%, 7.6%, 6.9%, and 7.6%, respectively. Compared with the referent category (>35th to 65th percentile group), higher percentile categories were positively associated with the prevalence of wheeze. A U-shaped relationship between BMI and asthma was observed. No material associations between BMI percentile categories and the prevalence of eczema or rhinoconjunctivitis were found. These findings suggested that being either underweight or overweight might increase the likelihood of asthma among Japanese schoolchildren.


Minimal Detectable Change for the ImPACT Test Administered Remotely.
Immediate Postconcussion Assessment and Cognitive Testing (ImPACT) is one of the most widely used computerized neurocognitive assessment batteries in athletics and serves as both a baseline and postinjury assessment. It has become increasingly popular to administer the ImPACT baseline test in an unsupervised remote environment; however, whether the lack of supervision affects the test-retest reliability is unknown. To establish the minimal detectable change (MDC) of composite scores from the ImPACT test when administered to National Collegiate Athletic Association Division I student-athletes in an unsupervised remote environment before 2 consecutive athletic seasons. Cross-sectional study. Participants were provided with a unique link and detailed written instructions on how to complete the ImPACT test at home. Division I student-athletes. Remote baseline ImPACT results from the 2020-2021 and 2021-2022 athletic seasons were analyzed. The MDC was calculated at the 95%, 90%, and 80% CIs for each of the ImPACT composite scores as well as the average and SD. The MDC at the 95% CI was 18.6 for the verbal memory composite score, 24.44 for visual memory, 8.76 for visual motor, 0.14 for reaction time, and 6.13 for impulse control. One-way repeated-measures multivariate analysis of variance, repeated-measures analysis of variance, and Wilcoxon signed ranks tests suggested no difference in the composite scores and impulse control between time points. The ImPACT composite scores and impulse control did not change between the 2 remote testing time points when administered approximately 1 year apart. Our study suggests that the MDC serves as a clinician's guide for evaluating changes in ImPACT baseline scores and in making clinical judgments on sport-related concussion when the test is administered at home.


Genetic dissection of a major QTL for kernel weight spanning the Rht-B1 locus in bread wheat.
Genetic dissection uncovered a major QTL QTKW.caas-4BS corresponding with a 483 kb deletion that included genes ZnF, EamA and Rht-B1. This deletion was associated with increased grain weight and semi-dwarf phenotype. Previous studies identified quantitative trait loci (QTL) for thousand kernel weight (TKW) in the region spanning the Rht-B1 locus in wheat (Triticum aestivum L.). We recently mapped a major QTL QTKW.caas-4BS for TKW spanning the Rht-B1 locus in a recombinant inbred line (RIL) population derived from Doumai/Shi 4185 using the wheat 90K array. The allele from Doumai at QTKW.caas-4BS significantly increased TKW and kernel number per spike, and conferred semi-dwarf trait, which was beneficial to improve grain yield without a penalty to lodging. To further dissect QTKW.caas-4BS, we firstly re-investigated the genotypes and phenotypes of the RILs and confirmed the QTL using cleaved amplified polymorphic sequence (CAPS) markers developed from flanking SNP markers IWA102 and IWB54814. The target sequences of the CAPS markers were used as queries to BLAST the wheat reference genome RefSeq v1.0 and hit an approximate 10.4 Mb genomic region. Based on genomic mining and SNP loci from the wheat 660K SNP array in the above genomic region, we developed eight new markers and narrowed QTKW.caas-4BS to a genetic interval of 1.5 cM. A 483 kb deletion in Doumai corresponded with QTKW.caas-4BS genetically, including three genes ZnF, EamA and Rht-B1. The other 15 genes with either differential expressions and/or sequence variations between parents were also potential candidate genes for QTKW.caas-4BS. The findings not only provide a toolkit for marker-assisted selection of QTKW.caas-4BS but also defined candidate genes for further functional analysis.


Description of a new species, Toxorhynchites (Toxorhynchites) tyagii (Diptera: Culicidae), from Nilgiri hills, Western Ghats, southern India.
Specimens of Toxorhynchites (Toxorhynchites) tyagii, sp. n., were collected from the fringe areas of Gudaloor town, Ooty in the Nilgiri hills at an altitude of 1000 m above sea level in Western Ghats ranges in southern India during October 2011 and from Darjeeling ranges in the northern hilly region of Raymatang TG in Jalpaiguri district, West Bengal, in eastern India during February 2012. The adults, pupa and fourth-instar larva of this species are described and illustrated to distinguish it from Toxorhynchites (Tox.) splendens and Toxorhynchites (Tox.) edwardsi, which are the closest allies of Tx. (Tox.) tyagii. Besides possessing remarkable distinguishing male genital characteristics, Tx. tyagii differs from Tx. splendens also by the presence of conspicuous yellow scale-patches over the wing root that extend to the scutellum, and differs from Tx. edwardsi by having midtarsomeres 3-5 all dark whereas in Tx. edwardsi tarsomeres 3 and 4 and a larger part of 5 are white.


A model for colour preference behaviour of spring migrant aphids.
Aphids are economically and ecologically important herbivorous insects. A critical step in their life cycle is the visually guided host finding behaviour. To elucidate the role of colour in host finding of aphid spring migrants we conducted large colour trap experiments in the field and analysed aphid catch data, using trap spectral reflectance data as input. Based on known and putative photoreceptor sensitivities we developed and optimized a simple empirical colour choice model for spring migrants of different aphid species which confirmed and explained the yellow preference of these insects. In a further step, we applied multivariate statistical methods to behavioural and reflectance data, but without data on photoreceptor sensitivities, to find the wavelengths of greatest importance for the aphids' behavioural responses. This analysis confirmed the position of the green photoreceptor peak previously obtained independently with electrophysiological methods. In a final step, we applied the colour preference model to a dataset of leaf spectra. This showed that aphid visual preference would be dependent on the plants' nutritional status, with lower nitrogen input being associated with stronger preference, despite known benefits of high nitrogen levels for aphid reproduction and fitness. Ecological and evolutionary implications of these results are discussed. This article is part of the theme issue 'Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods'.


How to continue COVID-19 vaccine clinical trials? The ethics of vaccine research in a time of pandemic.
Between December 2020 and March 2021, the US Food and Drug Administration and the European Medicines Agency issued Emergency Use Authorizations and Conditional Marketing Authorizations for the distribution of the first COVID-19 vaccines. Although these vaccines were thoroughly assessed before their approval, regulators required companies to continue ongoing placebo-controlled clinical trials in order to gather further reliable scientific information on their safety and efficacy, as well as to start new studies to evaluate additional candidates. The aim of this paper is to present and discuss the ethical issues raised by the tension between the need to continue these types of clinical trials and the obligations related to the protection of the rights and well-being of research participants. Specifically, we question whether-how, and to what extent-fundamental principles governing research involving human beings can be applied to the current pandemic situation. We argue that continuing ongoing placebo-controlled clinical trials can be considered ethically justifiable only if all participants are adequately informed of any developments that may affect their willingness to remain enrolled, including the current situation of resource scarcity and the prioritization criteria established for vaccination. However, we also argue that currently approved vaccines, which are considered safe and effective enough to be administered to millions of people as part of the vaccination campaign, necessarily represent the "best proven intervention" currently available and, therefore, should be used as comparators in future studies instead of placebo.


Plasma membrane form of phosphatidate phosphohydrolase: a possible role in signal transduction during liver fibrogenesis.
1. Several growth factors important in liver regeneration and fibrosis stimulate phospholipase D in plasma membranes via a receptor/G-protein-coupled mechanism resulting in hydrolysis of phosphatidylcholine to phosphatidate. Phosphatidate can be further hydrolysed to diacylglycerol by phosphatidate phosphohydrolase. Phosphatidate and diacylglycerol can act as 'second-messengers' and regulation of phosphatidate phosphohydrolase activity could control the balance between them. 2. A form of phosphatidate phosphohydrolase, located in the plasma membrane and insensitive to inhibition by N-ethylmaleimide, has recently been identified that is distinct from the 'metabolic' form, which is present in the cytosol and microsomes and is sensitive to N-ethylmaleimide. 3. We have investigated the hypothesis that the balance between regeneration and fibrosis is, in part, determined by the activity of plasma membrane phosphatidate phosphohydrolase through its effect on the phosphatidate/diacylglycerol ratio. N-Ethylmaleimide-insensitive and -sensitive phosphatidate phosphohydrolase activities were measured in three hepatic conditions characterized by regeneration and/or fibrosis: alcoholic liver disease in humans (regeneration and fibrosis) and rat livers after either acute CCl-4-induced injury (regeneration) or common bile duct ligation (fibrosis). 4. In patients with alcoholic liver disease, N-ethylmaleimide-insensitive phosphatidate phosphohydrolase activity was higher in cirrhotic biopsies (5.82 +/- 0.3 nmol of Pi min-1 mg-1 of protein, n = 19) than in non-cirrhotic biopsies (2.17 +/- 0.2, n = 23) or in wedge biopsies from healthy subjects undergoing routine cholecystectomy (2.16 +/- 0.5, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)


Medicaid program; withholding of Medicaid payments for fraud or willful misrepresentation--HHS. Final rule.
This final rule specifically encourages State Medicaid agencies to whithhold program payments to providers without first granting administrative review where the State agency has reliable evidence of fraudulent activity by the provider. These changes serve both to reinforce and strengthen existing State Medicaid agency responsibilities in the withholding of program funds, and to bring Medicaid program regulations in line with existing Medicare policy in this area.


Antibacterial activity of curcumin and its essential nanoformulations against some clinically important bacterial pathogens: A comprehensive review.
Multidrug-resistant bacterial infections can kill 700,000 individuals globally each year and is considered among the top 10 global health threats faced by humanity as the arsenal of antibiotics is becoming dry and alternate antibacterial molecule is in demand. Nanoparticles of curcumin exhibit appreciable broad-spectrum antibacterial activity using unique and novel mechanisms and thus the process deserves to be reviewed and further researched to clearly understand the mechanisms. Based on the antibiotic resistance, infection, and virulence potential, a list of clinically important bacteria was prepared after extensive literature survey and all recent reports on the antibacterial activity of curcumin and its nanoformulations as well as their mechanism of antibacterial action have been reviewed. Curcumin, nanocurcumin, and its nanocomposites with improved aqueous solubility and bioavailability are very potential, reliable, safe, and sustainable antibacterial molecule against clinically important bacterial species that uses multitarget mechanism such as inactivation of antioxidant enzyme, reactive oxygen species-mediated cellular damage, and inhibition of acyl-homoserine-lactone synthase necessary for quorum sensing and biofilm formation, thereby bypassing the mechanisms of bacterial antibiotic resistance. Nanoformulations of curcumin can thus be considered as a potential and sustainable antibacterial drug candidate to address the issue of antibiotic resistance.


The use of a polylactide-based copolymer as a temporary skin substitute in deep dermal burns: 1-year follow-up results of a prospective clinical noninferiority trial.
Deep dermal burns can be covered with different kind of materials and techniques; one of them is a polylactide-based temporary skin substitute. The aim of this study was to intraindividually compare its 1-year outcome with the results obtained by use of autologous skin grafts in patients suffering from deep dermal burns. A prospective noninferiority trial was designed in order to assess skin quality and scar formation by use of subjective (Vancouver Scar Scale; Patient and Observer Scar Assessment Scale) and objective (noninvasive cutometry) burn scar assessment tools. All items of the Patient and Observer Scar Assessment Scale, except vascularity, were found to be noninferior in the areas covered with the temporary skin substitute vs. autologous skin. Results of objective scar evaluation showed comparable viscoelastic parameters without reaching noninferiority. Overall, the outcome of deep dermal burns covered with a polylactide-based temporary skin substitute revealed satisfactory results in terms of scar formation and skin quality as compared with autologous skin. This paper supports its use in deep dermal burns, where autologous skin donor sites require either to be reserved for coverage of full-thickness skin defects in severe burns or to be saved for reduction of additional morbidity in selected patient collectives.


Covalent linkages between cellulose and lignin in cell walls of coniferous and nonconiferous woods.
Covalent linkages between wall polysaccharides and lignin, especially linkage between cellulose and lignin were discussed by carboxymethylation technique of whole cell walls of coniferous and nonconiferous woods. Hydroxyl groups of plant cell walls polysaccharides were highly substituted, but not those of lignin by carboxymethyl groups under the used conditions, and separated into water-soluble and insoluble fractions by water extraction. Carboxymethylated wall polysaccharides linked covalently with lignin were distributed into the water-insoluble fractions. Composition of carboxymethylated sugar residues in the both fractions was analyzed quantitatively by 1H NMR spectroscopy after hydrolyzation with D2SO4 in D2O. More than half of cellulose linked covalently with lignin in coniferous wood, but only one-sixth of cellulose was involved in the linkage in nonconiferous wood. The major noncellulosic wall polysaccharides of coniferous wood also linked significantly with lignin. On the other hand, noncellulosic wall polysaccharides of nonconiferous wood were involved slightly in the covalent linkage with lignin. The situation of linkage between wall polysaccharides containing cellulose and lignin was visualized by scanning electron micrographs.


Patterning of muscle acetylcholine receptor gene expression in the absence of motor innervation.
The patterning of skeletal muscle is thought to depend upon signals provided by motor neurons. We show that AChR gene expression and AChR clusters are concentrated in the central region of embryonic skeletal muscle in the absence of innervation. Neurally derived Agrin is dispensable for this early phase of AChR expression, but MuSK, a receptor tyrosine kinase activated by Agrin, is required to establish this AChR prepattern. The zone of AChR expression in muscle lacking motor axons is wider than normal, indicating that neural signals refine this muscle-autonomous prepattern. Neuronal Neuregulin-1, however, is not involved in this refinement process, nor indeed in synapse-specific AChR gene expression. Our results demonstrate that AChR expression is patterned in the absence of innervation, raising the possibility that similarly prepatterned muscle-derived cues restrict axon growth and initiate synapse formation.


Applicability of the comet assay in evaluation of DNA damage in healthcare providers' working with antineoplastic drugs: a systematic review and meta-analysis.
Unintended occupational exposure to antineoplastic drugs (ANDs) may occur in medical personnel. Some ANDs are known human carcinogens and exposure can be monitored by genotoxic biomarkers. To evaluate the obstacles to obtaining conclusive results from a comet assay test to determine DNA damage among AND exposed healthcare workers. We systematically reviewed studies that used alkaline comet assay to determine the magnitude and significance of DNA damage among health care workers with potential AND exposure. Fifteen studies were eligible for review and 14 studies were used in the meta-analysis. Under random effect assumption, the estimated standardized mean difference (SMD) in the DNA damage of health care workers was 1.93 (95% CI: 1.15-2.71, p < 0.0001). The resulting SMD was reduced to 1.756 (95% CI: 0.992-2.52, p < 0.0001) when the analysis only included nurses. In subgroup analyses based on gender and smoking, heterogeneity was observed. Only for studies reporting comet moment, I2 test results, as a measure of heterogeneity, dropped to zero. Heterogeneity analysis showed that date of study publication was a possible source of heterogeneity (B = -0.14; p < 0.0001). A mixture of personal parameters, comet assay methodological variables, and exposure characteristics may be responsible for heterogenic data from comet assay studies and interfere with obtaining conclusive results. Lack of quantitative environmental exposure measures and variation in comet assay protocols across studies are important obstacles in generalization of results.


Adsorption of Respiratory Syncytial Virus, Rhinovirus, SARS-CoV-2, and F+ Bacteriophage MS2 RNA onto Wastewater Solids from Raw Wastewater.
Despite the widespread adoption of wastewater surveillance, more research is needed to understand the fate and transport of viral genetic markers in wastewater. This information is essential for optimizing monitoring strategies and interpreting wastewater surveillance data. In this study, we examined the solid-liquid partitioning behavior of four viruses in wastewater: SARS-CoV-2, respiratory syncytial virus (RSV), rhinovirus (RV), and F+ coliphage/MS2. We used two approaches: (1) laboratory partitioning experiments using lab-grown viruses and (2) distribution experiments using endogenous viruses in raw wastewater. Partition experiments were conducted at 4 and 22 °C. Wastewater samples were spiked with varying concentrations of each virus, solids and liquids were separated via centrifugation, and viral RNA concentrations were quantified using reverse-transcription-digital droplet PCR (RT-ddPCR). For the distribution experiments, wastewater samples were collected from six wastewater treatment plants and processed without spiking exogenous viruses; viral RNA concentrations were measured in wastewater solids and liquids. In both experiments, RNA concentrations were higher in the solid fraction than the liquid fraction by approximately 3-4 orders of magnitude. Partition coefficients (KF) ranged from 2000-270,000 mL·g-1 across viruses and temperature conditions. Distribution coefficients (Kd) were consistent with results from partitioning experiments. Further research is needed to understand how virus and wastewater characteristics might influence the partitioning of viral genetic markers in wastewater.


Adaptation of Nodulated Soybean (Glycine max L. Merr.) to Growth in Rhizospheres Containing Nonambient pO(2).
Nodulated soybean (Glycine max L. Merr. cv White Eye inoculated with Bradyrhizobium japonicum strain CB 1809) plants were cultured in the absence of combined N from 8 to 28 days with their root systems maintained continuously in 1, 2.5, 5, 10, 20, 40, 60, or 80% O(2) (volume/volume) in N(2). Plant dry matter yield was unaffected by partial pressure of oxygen (pO(2)) and N(2) fixation showed a broad plateau of maximum activity from 2.5 to 40 or 60% O(2). Slight inhibition of nitrogenase activity occurred at 1% O(2) and as much as 50% inhibition occurred at 80% O(2). Low pO(2) (less than 10%) decreased nodule mass on plants, but this was compensated for by those nodules having higher specific nitrogenase activities. Synthesis and export of ureides in xylem was maintained at a high level (70-95% of total soluble N in exudate) over the range of pO(2) used. Measurements of nitrogenase (EC 220.127.116.11) activity by acetylene reduction indicated that adaptation of nodules to low pO(2) was largely due to changes in ventilation characteristics and involved increased permeability to gases in those grown in subambient pO(2) and decreased permeability in those from plants cultured with their roots in pO(2) greater than ambient. A range of structural alterations in nodules resulting from low pO(2) were identified. These included increased frequency of lenticels, decreased nodule size, increased volume of cortex relative to the infected central tissue of the nodule, as well as changes in the size and frequency of extracellular voids in all tissues. In nodules grown in air, the inner cortex differentiated a layer of four or five cells which formed a band, 40 to 50 micrometers thick, lacking extracellular voids. This was reduced in nodules grown in low pO(2) comprising one or two cell layers and being 10 to 20 micrometers thick in those from 1% O(2). Long-term adaptation to different external pO(2) involved changes which modify diffusive resistance and are additional to adjustments in the variable diffusion barrier.


Outcomes and factors influencing survival in cirrhotic cases with spontaneous rupture of hepatocellular carcinoma: a multicenter study.
Spontaneous rupture is rare complication of hepatocellular carcinoma (HCC) with high mortality rate in cirrhotic cases. The aim of this study was to determine the factors influencing prognosis in cases of spontaneously ruptured HCC and to investigate the outcomes of the treatments employed, especially transcatheter arterial embolization (TAE). A retrospective multicenter study was conducted in 48 cirrhotic patients with spontaneous rupture of HCC. Conservative treatment was employed in 32 patients (ConT group) and TAE was performed in 16 patients (TAE group). The median survival time (MST) in the ConT group was only 13.1 days and the survival rate was extremely poor: 59.4% at 7 days, 37.5% at 14 days, and 6.3% at 30 days. On the other hand, the MST in the TAE group was 244.8 days and the survival rate was 87.5% at 1 month, 56.3% at 3 months, 23.4% at 12 months, and 15.6% at 24 months. According to the results of univariate analyses, factors associated with poor hepatic function and poor suitability for TAE was important determinants of short-term death (less than 3 weeks) among the patients (p < 0.05). On the other hand, among the patients in whom initial TAE was successfully performed (n = 15), a multivariate analysis showed that a maximum tumor size not exceeding 7 cm was the only independent factor determining long-term survival (p = 0.0130). Despite the inherent limitations of this retrospective study, TAE appears to be a useful treatment strategy for cirrhotic patients with spontaneous HCC rupture, as it yielded a longer survival period compared with conservative treatment in patients with ruptured HCC. Among the patients with ruptured HCC in whom initial TAE was successfully performed, the maximum tumor size was an important factor influencing survival.


Observation of nanophase segregation in LiCl aqueous solutions from transient grating experiments.
Transient grating experiments performed on supercooled LiCl, RH2O solutions with R > 6 reveal the existence of well resolved, short time, extra signal which superposes to the normal signal observed for the R = 6 solution and for homogenous glass forming systems. This extra signal shows up below 190 K, its shape and the associated timescale depend only on temperature, while its intensity increases with R. We show that the origin of this signal is a phase separation between clusters with a low solute concentration and the remaining, more concentrated, solution. Our analysis demonstrates that these clusters have a nanometer size and a composition which are rather temperature independent, while increasing R simply increases the density of these clusters.


Phage Annotation Guide: Guidelines for Assembly and High-Quality Annotation.
All sequencing projects of bacteriophages (phages) should seek to report an accurate and comprehensive annotation of their genomes. This article defines 14 questions for those new to phage genomics that should be addressed before submitting a genome sequence to the International Nucleotide Sequence Database Collaboration or writing a publication.


Factors Contributing to Poor Self-Rated Health in Older Adults with Lower Income.
Lower household income is associated with poorer self-reported health status, especially in the elderly. Considering the importance of subjective health in this fragile population, it would be worthwhile to explore the physical and mental health factors that may help to predict good or poor self-rated health (SRH) status. We first described three main categories (individual, physical, and psychological) between low-income seniors with good and poor SRH. Next, statistically significant physical and mental health factors affecting poor SRH were identified. In this study, original data from the 2017 National Survey of Older Persons in South Korea were analyzed. People aged 65 years and over with low household income were eligible. A total of 1405 men and 2945 women (n = 4350) were enrolled, and less than half of participants (47.5%, n = 2066) belonged to the poor SRH cohort. We applied individual variable-adjusted models and found that poor SRH was significantly associated with ADL limitation (odds ratio (OR): 2.91, 95% confidence interval (CI) 2.11-4.01), IADL limitation (OR: 1.80, 95% CI: 1.52-2.13), malnutrition (OR: 1.76, 95% CI: 1.53-2.04), and depression (OR: 3.65, 95% CI: 3.10-4.31) on logistic regression analysis. Our findings suggest that limited ADL/IADL, poor nutrition, and depression need to be emphasized to improve subjective health status in low-income adults. Early recognition and timely intervention might help them to live better and happier, ultimately relieving social healthcare burdens.


Thrombosis in systemic lupus erythematosus: a French collaborative study.
A retrospective study was undertaken of 120 children with systemic lupus erythematosus (SLE) seen in Paris and its immediate suburbs who fulfilled at least four of the American College of Rheumatology diagnostic criteria for SLE, and in whom the disease was diagnosed before the age of 16 and between January 1975 and December 1987. Eleven of these children (eight girls and three boys) all more than 10 years of age (mean follow up 8.1 years; range 3-13) had thrombotic episodes (9%). Thrombosis was one of the presenting signs in seven patients; in five it was associated with typical symptoms of SLE, and in the other two the thrombotic episode was isolated and diagnosis of SLE was delayed one and three years. Of a total of 16 thrombotic episodes (six of which were recurrent), 14 involved the leg veins, and in four there was associated pulmonary embolism. There were two episodes that affected cerebral arteries. The American College of Rheumatology diagnostic criteria for SLE as well as the incidence of lupus anticoagulant, positive direct Coombs test, and vasculitis in this group of patients was compared with the incidence in patients with SLE but no thrombosis. Only lupus anticoagulant was significantly associated with thrombotic episodes: eight of 11 (73%) of patients with SLE and thrombotic (arterial or venous) episodes had lupus anticoagulant compared with only 10 of 74 patients (14%) with no history of thrombotic events in the same age group.


Preserving the humanities in medical education.
Patients are frequently unhappy with medical care because physicians fail to demonstrate humanistic qualities. Immersion in science is a necessary part of medical education but not sufficient. Courses in the history of medicine, the medical narrative in literature, bioethics, medicine and art, and spirituality and medicine will train physicians who will temper technological medicine with a humanistic touch. The rapid growth in biomedical knowledge and the growing demands upon medical students' time threaten to crowd out time for the humanities. Furthermore, the financing of medical humanities programmes is often tenuous. Medical students must come to understand that much of medical knowledge is a function of time and place, that medicine is a profoundly social enterprise and that the practice of medicine is a value-laden undertaking. The preservation of programmes in the medical humanities will reinforce the social responsibility that should be inherent in medical education.


[The early diagnosis of intestinal ischemia by gammagraphic study].
Intestinal wall necrosis without perforation was produced in six dogs. Another group of three dogs served as a control. The histologic findings, the degree of ischemia and scintigraphic images obtained after the infusions of autologous white blood cells labelled with indium-111 oxine were correlated. Positive scans were obtained in all the dogs with proven intestinal ischemia. Negative scans appeared in the dogs without ischemic insult and a false-positive scan were observed in a control dog with diarrhea.


[General awareness and use of generic medication among citizens of Tubarão, state of Santa Catarina, Brazil].
Although generic medication has been introduced in the country to offer an accessible alternative to brand-name medication, it represents only 14% of sales in number of units within the pharmaceutical market. The aim of this work was to research the level of awareness and the use of generic products among residents of the municipality of Tubarão, State of Santa Catarina, Brazil. A transversal study was carried out with a sample of 234 interviewees, distributed among municipal areas. With regard to use, the majority of those interviewed had used generic medication, and half of them had at least one such product in their home. To verify awareness of different types of medication, pictures with the generic, brand name and similar packaging for paracetamol and atenolol were shown and 91% were able to identify all products correctly. To be of higher economic standing, already having used generic products, believing that the generic medication has the same effect as the brand name medication, finding generic products in drugstores easily and being accustomed to buy generic products, were factors that were positively associated with the correct identification.


Infection control in the dental laboratory: a review of the literature.
The dental laboratory has been shown to be an area of potential disease transmission between patients and to laboratory personnel. This paper reviews pertinent literature on the subject and describes the "Barrier System," a proven infection control protocol to manage dental prostheses in the laboratory.


Sulfonamide Derived Esters: Synthesis, Characterization, Density Functional Theory and Biological Evaluation through Experimental and Theoretical Approach.
A series of new solid esters was synthesized by using greener chemistry strategy involving simple reaction of an alcohol with sulfonamide ligand. Characterization study of these methyl (1), ethyl (2) isopropyl (3) and n-butyl (4) ester of 4-((4-chlo-rophenylsulfonamido)methyl)cyclohexanecarboxylic acid was done by using FTIR, NMR mass spectrometry and X-ray crystallography. The compounds were optimized with Gaussian software according to basis set B3LYP/6-31G(d,p) and their different parameters related to structure were calculated. Furthermore, all compounds of the series were screened for their in vitro biological applications involving anti-bacterial (Chromohalobactor salixgens, Halomonas halofila, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Shiegella sonnei), anti-fungal (Aspergillus niger), anti-oxidant (DPPH scavenging activity) and enzyme inhibition (acetylcholine esterase and butyrylcholine esterase) study. Sulfonamide based esters were also docked against selected enzymes (AChE and BChE) using MOE software for their mode of binding. Results obtained from these biological evaluations showed that such compounds have potential against targeted activity.


Advances in the understanding of mechanisms and therapeutic use of bortezomib.
The ubiquitin-proteasome pathway regulates many basic cellular processes and has been proven to be a promising target for cancer therapy. Bortezomib is the first U.S. Food and Drug Administration (FDA) approved proteasome inhibitor used in the treatment of newly diagnosed multiple myeloma, relapsed/refractory multiple myeloma, and mantle cell lymphoma. The anti-cancer mechanisms of bortezomib elucidated by preclinical studies include: upregulation of proapoptotic proteins (e.g., Noxa, IκB), inhibition of NFκB and its anti-apoptotic target genes, suppression of several anti-apoptotic proteins (e.g., Bcl-XL, Bcl-2, and STAT-3), down-regulation of expression of several proteins involved in DNA repair pathways, and induction of endoplasmic reticulum (ER) stress and pro-apoptotic Unfolded Protein Response (UPR). Bortezomib has potent chemo-/radio-sensitizing effects and can overcome traditional drug resistance in tumors when used in combination with potential chemotherapies. Although bortezomib has been successful in improving clinical outcomes when used in hematological malignancies, relapse may occur in those patients who responded initially. Furthermore, some cytotoxicities (such as peripheral neuropathy) were found to be associated with bortezomib treatment. These observations have encouraged researchers to search for the next generation proteasome inhibitors (including carfilzomib and marizomib) that could overcome bortezomib resistance and have improved properties, reduced toxicities, and broader anticancer activities, based on the lessons learned from the mechanisms and use of bortezomib. This review summarizes the current status of bortezomib as well as several other proteasome inhibitors that are currently under clinical and preclinical investigation.


A latent transition analysis of bullying and victimization in Chinese primary school students.
Bullying is a social phenomenon that impacts a large number of children and young people, worldwide. This study aimed to longitudinally examine the development of bullying and victimization in Chinese students in grades 4, 5, and 6. We used latent class analysis to empirically identify groups of youth with different bullying and victimization patterns, and then used latent transition analysis to explore the movement of children between these latent classes over time. Results showed that: (1) across the three time points, students could be classified into four classes: bullies, victims, bully-victims, and non-involved children; and (2) students in the non-involved class tended to remain in that class when moving to higher grades, students in the bully and victims classes tended to transition to the non-involved class, while students in the bully-victims class tended to transition to the bullies class. Thus, future intervention should be implemented to prevent bully-victims from bullying behaviors.


Detection and localization of protein-acetaldehyde adducts in rat brain after chronic ethanol treatment.
Ethanol is metabolized to acetaldehyde in the cell, which is potentially deleterious because it can react with cellular proteins and form protein-acetaldehyde adducts, which can interfere with normal cellular function. Because the primary site of ethanol action is the brain, the present study was carried out to determine whether protein-acetaldehyde adducts are formed in rat brain after chronic ethanol administration. Rats were treated with ethanol for 1 year, and the formation of protein-acetaldehyde adducts was examined by immunoblot analysis and localized in brain by immunohistochemical analysis by using affinity purified antibody to acetaldehyde-hemocyanin adduct. In the brain of rats administered ethanol for up to 1 year, protein-acetaldehyde adducts were detectable by immunoblot analysis. In brain, mitochondria was the primary site of adduct formation, unlike the liver, where the major protein-acetaldehyde adduct has been detected in the cytosol. Immunohistochemical localization of protein-acetaldehyde adducts in chronic ethanol-treated rat brain demonstrated the selective presence of adducts in cortical neurons, granule cell layer of dentate gyrus, neurons in the midbrain, and granular cell layers of cerebellum. These results demonstrate the significant formation of protein-acetaldehyde adducts in rat brain after ethanol ingestion. The modification of mitochondrial proteins in brain by protein-acetaldehyde adduct formation is significant because mitochondrial dysfunction has been implicated in neurodegeneration.


Assembly of indole-2-carboxylic acid esters through a ligand-free copper-catalysed cascade process.
A straightforward synthesis of indole-2-carboxylic esters was developed through a ligand-free copper-catalysed condensation/coupling/deformylation cascade process from 2-halo aryl aldehydes or ketones with ethyl isocyanoacetate. The reactions proceeded well for most of the 2-iodo-, bromo-, and chloro-substrates under room temperature or mild conditions.


Genetic and environmental influences on impulsivity: a meta-analysis of twin, family and adoption studies.
A meta-analysis of twin, family and adoption studies was conducted to estimate the magnitude of genetic and environmental influences on impulsivity. The best fitting model for 41 key studies (58 independent samples from 14 month old infants to adults; N=27,147) included equal proportions of variance due to genetic (0.50) and non-shared environmental (0.50) influences, with genetic effects being both additive (0.38) and non-additive (0.12). Shared environmental effects were unimportant in explaining individual differences in impulsivity. Age, sex, and study design (twin vs. adoption) were all significant moderators of the magnitude of genetic and environmental influences on impulsivity. The relative contribution of genetic effects (broad sense heritability) and unique environmental effects were also found to be important throughout development from childhood to adulthood. Total genetic effects were found to be important for all ages, but appeared to be strongest in children. Analyses also demonstrated that genetic effects appeared to be stronger in males than in females. Method of assessment (laboratory tasks vs. questionnaires), however, was not a significant moderator of the genetic and environmental influences on impulsivity. These results provide a structured synthesis of existing behavior genetic studies on impulsivity by providing a clearer understanding of the relative genetic and environmental contributions in impulsive traits through various stages of development.


Renal diseases in haemophilic patients: pathogenesis and clinical management.
Haemophilia A and B are genetic X-linked bleeding disorders, caused by mutations in genes encoding factors VIII and IX, respectively. Clinical manifestations of haemophilia are spontaneous haemorrhage or acute bleeding caused by minor trauma, resulting in severe functional consequences that can culminate in a debilitating arthropathy. Life expectancy and quality of life of patients with haemophilia have dramatically improved over the last years, mainly for new therapeutic options and the awareness to the risk of HCV and HIV infections. Different clinical problems arise from this important change in history of patients with haemophilia. In particular, ageing-related diseases, such as diabetes, hypertension and cancer, and chronic viral infections are emerging as new challenges in this patient population. Among the different types of chronic illnesses, renal diseases are of special interest as they involve some difficult management issues. In fact, decisions regarding adequate preventive strategies and viral infection treatment, the choice of the dialytic modality, placement of vascular access and prescription of dialytic treatments are particularly complicated, because only few data are available. In this review, we discuss the pathogenesis of renal damage in patients with haemophilia, especially in those with blood-transmitted viral infections, and the major issues about the management of renal diseases, including problems related to dialytic treatment and kidney transplantation, providing practical algorithms to guide the clinical decision-making process.