Polydopamine-coated nanocomposite theranostic implants for localized chemotherapy and MRI imaging.
Sustained and localized delivery of chemotherapeutics in postoperative cancer treatment leads to a radical improvement in prognosis and a much decreased risk of tumor recurrence. In this work, polydopamine (PDA)-coated superparamagnetic iron oxide nanoparticle (SPION)-loaded polycaprolactone and poly(lactic-co-glycolic acid) fibers were developed as a potential implant to ensure safe and sustained release of the chemotherapeutic drug methotrexate (MTX), as well as provide local contrast for magnetic resonance imaging (MRI). Fibres were prepared by co-axial electrospinning and loaded with MTX-layered double hydroxide (LDH) nanocomposites in the core, yielding organic-inorganic hybrids ranging from 1.23 to 1.48 µm in diameter. After surface coating with PDA, SPIONs were subsequently loaded on the fibre surface and found to be evenly distributed, providing high MRI contrast. In vitro drug release studies showed the PDA coated fibres gave sustained release of MTX over 18 days, and the release profile is responsive to conditions representative of the tumor microenvironment such as slightly acidic pH values or elevated concentrations of the reducing agent glutathione (GSH). In vitro studies with Caco-2 and A549 cells showed highly effective killing with the PDA coated formulations, which was further enhanced at higher levels of GSH. The fibres hence have the potential to act as an implantable drug-eluting platform for the sustained release of cytotoxic agents within a tumor site, providing a novel treatment option for post-operative cancer patients.


Impaired rearrangement of IgH V to DJ segments in bone marrow Pro-B cells from old mice.
There are fewer bone marrow Pre-B cells in old compared to young mice. We have demonstrated both decreased rearrangement of the V to DJ IgH gene segments and low levels of VH germline transcripts in Pro-B cells, the precursors of Pre-B cells, from old compared to young mice. However, there was no difference in the level of RAG-mRNA in purified Pro-B cells from old and young mice. Consistent with the prior reports that fewer bone marrow emigrants enter the peripheral B cell populations of old than young mice, we identified fewer transitional B cells in the blood, as well as the spleen, of old than young mice. Association of impaired IgH rearrangement with a decreased number of transitional B cells in old mice was supported by finding that the percentage and number of transitional B cells expressing rearranged IgH and IgL transgenes, which do not require rearrangement of their endogenous IgH gene segments, were comparable in old and young mice. In contrast, the percentage and number of transitional B cells in these Ig-transgenic mice, which escaped allelic exclusion and have rearranged endogenous IgH gene segments, showed an age-associated decline similar to that seen in wild type mice. These data are consistent with the view that impaired V to DJ rearrangement contributes to the decreased levels of bone marrow Pre-B cells as well as the decreased levels of transitional B cells in the periphery.


Comparative analysis of the transcriptome during single-seed formation of Castanea henryi: regulation of starch metabolism and endogenous hormones.
In seed plants, the ovule is the precursor to the seed. The process of ovule development and differentiation is regulated by multiple factors, including starch metabolism and endogenous hormones. Castanea henryi produces nuts with high nutritional value. However, the high proportion of empty buds restricts the commercial use of the tree. Previous studies have shown that the empty bud phenotype is closely related to ovule abortion. If none of the ovules in the ovary expand rapidly and develop in 7-8 weeks after pollination, an empty bud will form. Therefore, we studied the development and molecular mechanisms underlying single seed formation in C. henryi. We found that 49 days after pollination (DAP) is a critical period for the formation of fertile and abortive ovules. The morphology and starch distribution of the fertile and abortive ovules differed significantly at 49 DAP. The fertile ovules were smooth and round in appearance, with a large amount of starch. In contrast, abortive ovules were smaller with only a small amount of starch. The embryo sac of the abortive ovule proceeded to develop abnormally, and the entire ovule lacked starch. We identified 37 candidate genes involved in metabolism with potential roles in the regulation of starch levels. Three ADP-glucose pyrophosphorylase (AGPase) genes, one granule-bound starch synthase (GBSS) gene, and two beta-amylase genes could affect starch accumulation. The levels of auxin, cytokinins, gibberellins, and jasmonic acid in fertile ovules were higher than those in abortive ovules. In addition, the levels of endogenous abscisic acid and salicylic acid in abortive ovules were higher than those in fertile ovules of the same age, consistent with the expression patterns of genes related to the synthesis of abscisic and salicylic acid and signal transduction. We identified and mapped the differentially expressed genes associated with hormone synthesis and signal transduction. These results improve our general understanding of the molecular mechanisms underlying single seed development in C. henryi and the phenomenon of empty buds, providing directions for future research.


Menstrual Irregularity, Hormonal Contraceptive Use, and Bone Stress Injuries in Collegiate Female Athletes in the United States.
Menstrual irregularity (MI) is common in female athletes and is a component of the Female Athlete Triad (Triad). Many athletes with the Triad are started on hormonal contraceptives (HC) for MI, but this interferes with the ability to monitor menstrual cycle regularity and can mask other causes of MI. There are limited studies investigating the relationship between MI, HC use, and injury in female collegiate athletes. To examine the prevalence of and relationship between HC use, MI, and bone stress injuries in female collegiate athletes in the United States. Cross-sectional study. Online survey. 1020 U.S. female collegiate athletes (age ≥ 18 years). Assessment of risk factors for menstrual irregularity and bone stress injuries was conducted via a one-time survey. HC use, MI, history of stress fractures. Current HC use prevalence was 65% (95% confidence interval [CI], 61.9%, 67.8%). Of all athletes, 47% reported past MI. Of the athletes who were not currently using HCs, 32% had current MI. Compared with athletes without past MI, more athletes with past MI reported current HC use (73% vs. 57%) and indicated menstrual cycle consistency as the primary reason for use (24% vs. 4%) (P < .001). Additionally, 25% of athletes reported a history of stress fractures, which was associated with lean/aesthetic sports participation (odds ratio [95% CI]: 1.9 [1.4, 2.5]; P < .001) and less oral contraceptive pill (OCP) use (0.7 [0.5, 1.0]; P = .043). Compared with OCPs, injectable HCs were associated with greater odds of a history of stress fractures (4.5[1.6, 12.3]; P = .004). HC use was prevalent among this cohort of female collegiate athletes, and almost half of the athletes reported past MI. A goal of menstrual cycle regularity was cited by 24% of athletes as a primary reason to use HCs, which shows that more athlete education is needed to avoid masking MI and the Triad with HCs. Further studies elucidating the relationship between HC use, MI, and sports-related injury are warranted.


Synovial sarcoma metastatic to the parotid gland: A possible pitfall in salivary gland fine needle aspiration cytology. Report of a case with immunocytochemical and fluorescence in situ hybridization findings.
We report one case of metastatic synovial sarcoma (SS) to the parotid gland in a 93-year-old male. The patient had undergone upper left pulmonary lobectomy with mediastinal lymphadenectomy for SS of the lung 5 years before. The cytopathologic presentation and the immunocytochemical findings on the FNA sample were suggestive of a spindle cell myoepithelioma, while a SYT rearrangement was identified by a FISH performed on a cytological smear of the lesion. The diagnosis was further confirmed also by positive immunocytochemical expression of TLE1 on a section from the obtained cell block. The cytologic and immunophenotypic findings are shortly discussed in view of the reported immunophenotypic inconsistency of SS and of its differential diagnosis with spindle cell myoepithelioma of the salivary glands.The importance of the recently described TLE1 staining and its close correlation to SYT rearrangement is briefly discussed.


SnapKin: a snapshot deep learning ensemble for kinase-substrate prediction from phosphoproteomics data.
A major challenge in mass spectrometry-based phosphoproteomics lies in identifying the substrates of kinases, as currently only a small fraction of substrates identified can be confidently linked with a known kinase. Machine learning techniques are promising approaches for leveraging large-scale phosphoproteomics data to computationally predict substrates of kinases. However, the small number of experimentally validated kinase substrates (true positive) and the high data noise in many phosphoproteomics datasets together limit their applicability and utility. Here, we aim to develop advanced kinase-substrate prediction methods to address these challenges. Using a collection of seven large phosphoproteomics datasets, and both traditional and deep learning models, we first demonstrate that a 'pseudo-positive' learning strategy for alleviating small sample size is effective at improving model predictive performance. We next show that a data resampling-based ensemble learning strategy is useful for improving model stability while further enhancing prediction. Lastly, we introduce an ensemble deep learning model ('SnapKin') by incorporating the above two learning strategies into a 'snapshot' ensemble learning algorithm. We propose SnapKin, an ensemble deep learning method, for predicting substrates of kinases from large-scale phosphoproteomics data. We demonstrate that SnapKin consistently outperforms existing methods in kinase-substrate prediction. SnapKin is freely available at https://github.com/PYangLab/SnapKin.


The role of simulated-experience and descriptive formats on perceiving risks of strong opioids: A randomized controlled trial with chronic noncancer pain patients.
Opioid prescription rates worldwide suggest miscalibrated risk perceptions among those who prescribe, dispense, and take opioids. Findings from cognitive science show that risk perceptions can differ systematically depending on whether people learn about risks by description or experience. We investigated the effects of descriptive and simulated experience risk formats on patients' risk perceptions and behavior regarding long-term strong opioid use. 300 German patients with chronic noncancer pain were randomly assigned in an exploratory randomized controlled trial to either a descriptive format (fact box) or a simulated experience format (interactive simulation). Primary endpoints were subjective and objective risk perceptions and intended intake behavior. Both formats significantly improved patients' objective risk perception; patients who saw the fact box estimated some outcomes more accurately (p = .031). Formats were equally effective in improving patients' subjective risk perception in terms of opioids' harms; however, patients receiving the simulation showed a greater reduction and termination of their opioid intake (p = .030) and a higher uptake of alternative therapies. Descriptive and simulated experience risk formats improve risk perceptions and behavior regarding potent but highly risky drugs. To eliminate risky behavior, simulated experience formats may be superior to descriptive formats.


Endosomal and non-endosomal functions of ESCRT proteins.
The three endosomal sorting complexes required for transport (ESCRTs) are integral to the degradation of endocytosed membrane proteins and multivesicular body (MVB) biogenesis. Here, we review evidence that ESCRTs have evolved as a specialized machinery for the degradative sorting of ubiquitinated membrane proteins and we highlight recent studies that have shed light on the mechanisms by which these complexes mediate protein sorting, MVB biogenesis, tumour suppression and viral budding. We also discuss evidence that some ESCRT subunits have evolved additional functions that are unrelated to membrane trafficking.


Dissociation between linguistic and nonlinguistic gestural systems: a case for compositionality.
This paper addresses the issue of the separability of disorders of sign language from disorders of gesture and pantomime. The study of a left-lesioned deaf signer presents one of the most striking examples to date of the cleavage between linguistic signs and manual pantomime. The left-hemisphere lesion produced a marked sign language aphasia disrupting both the production and the comprehension of sign language. However, in sharp contrast to the breakdown of sign language, the ability to communicate in nonlinguistic gesture was remarkably spared. This case has important implications for our understanding of the neural mediation of language and gesture. We argue that the differences observed in the fractionation of linguistic versus nonlinguistic gesture reflect differing degrees of compositionality of systems underlying language and gesture. The compositionality hypothesis receives support for the existence of phonemic paraphasias in sign language production, illustrating structural dissolution which is absent in the production of pantomimic gesture. Understanding the neural encoding of compositional motoric systems may lead to a principled anatomical account of the neural separability of language and gesture. This case provides a powerful indication of the left hemisphere's specialization for language-specific functions.


Effects of hydraulic retention time and nitrobenzene concentration on the performance of sequential upflow anaerobic filter and air lift reactors in treating nitrobenzene-containing wastewater.
Sequential upflow anaerobic filter (UAF)/air lift (ALR) reactors were employed to investigate the effects of hydraulic retention time (HRT) and nitrobenzene (NB) concentration on treatment of NB-containing wastewater. The results showed that NB was effectively reduced to aniline (AN) with glucose as co-substrate in the UAF reactor. The AN and the remaining intermediates after the UAF reactor were then efficiently degraded in the ALR reactor. A removal efficiency of 100% and 96% was obtained for NB and chemical oxygen demand (COD), respectively, using sequential UAF/ALR reactors with an HRT of 8-72 h in the UAF reactor and 2-18 h in the ALR reactor. The corresponding optimal influent NB concentration varied between 100 and 400 mg l(-1) to achieve the optimal NB and COD removal. The NB removal efficiency decreased to 90% and to 97% if the HRT in the UAF reactor decreased from 8 to 2 h and the influent NB concentration increased from 400 to 800 mg l(-1), respectively. The results showed that sequential UAF/ALR system can be operated at low HRTs and high NB concentrations without significantly affecting the removal efficiency of NB in the reactor system. The UAF/ALR system can provide an effective yet low cost method for treatment of NB-containing industrial wastewater.


Temozolomide and radiation in low-grade and anaplastic gliomas: temoradiation.
Recently completed trials suggest the addition of nitrosourea-based chemotherapy to radiotherapy increases the progression-free but not overall survival of grade II and III gliomas. Temozolomide has proven benefit in grade II/III gliomas progressive following standard therapy and when added to radiation for glioblastoma. Newly launched and planned phase III trials will explore whether the addition of temozolomide to radiotherapy improves overall survival in grade II/III as well as the prognostic and predictive value of 1p/19q analyses and MGMT promotor methylation status. Additionally, they will measure cognition and quality of life to determine if improvements in time to progression translate into better functional status and patient satisfaction.


Ionic permeability of epithelial tissues.
The overall permeability of epithelial tissues to solutes is generally determined by analyzing net or unidirectional transepithelial fluxes in response to transepithelial differences of concentration and/or electrical potential using relations that describe diffusional movements across a single membrane. If the solute is uncharged and diffusional movements are transcellular, the overall transepithelial permeability coefficient is determined by the permeabilities of the two limiting cell membranes combinded in series. However, if the solute is charged and the pathway for transepithelial movement involves diffusional flows across at least two membranes arranged in series (i.e. transcellular transport), the value of the overall transepithelial permeability coefficient determined using relations that describe ionic diffusion across a single membrane is not an accurate measure of the permeabilities of the two limiting membranes combined in series. Further, if ionic diffusion is transcellular, permeability coefficients determined from studies of transepithelial fluxes are not only quantitatively incorrect but can also result in grossly erroneous interpretations of changes in transepithelial permeabilities and faulty inferences regarding the route of transepithelial ionic diffusion.


Greater knee varus angle and pelvic internal rotation after landing are predictive factors of a non-contact lateral ankle sprain.
This study aimed to clarify the kinematic, kinetic characteristics associated with lateral ankle sprain. A 16-month prospective cohort study. Laboratory. A total of 179 college athletes. Joint kinematics, moment during single-leg landing tasks, and ankle laxity were measured. The attendance of each participating team, injury mechanism, existence of body contact, presence of orthosis, with or without medical diagnosis, and periods of absence were recorded. Twenty-nine participants incurred lateral ankle sprain during non-contact motion. The Cox regression analysis revealed that greater knee varus peak angle (hazard ratio: 1.16 [95% confidence interval: 1.10-1.22], p < 0.001) and greater pelvic internal rotation peak angle toward the support leg were associated with lateral ankle sprain (hazard ratio: 1.08 [95% confidence interval: 1.02-1.15], p = 0.009). The cut-off values for each predictive factor were -0.17° (area under the curve = 0.89, p < 0.001) and 6.63° (area under the curve = 0.74, p < 0.001), respectively. A greater knee varus peak angle and pelvic internal rotation peak angle after single-leg landing are predictive factors for lateral ankle sprain.


Pathogenesis of Plasmodium falciparum malaria: the roles of parasite adhesion and antigenic variation.
Malaria results in up to 2.5 million deaths annually, with young children and pregnant women at greatest risk. The great majority of severe disease is caused by Plasmodium falciparum. A characteristic feature of infection with Pfalciparum is the accumulation or sequestration of parasite-infected red blood cells (RBCs) in various organs, such as the brain, lung and placenta, and together with other factors is important in the pathogenesis of severe forms of malaria. Sequestration results from adhesive interactions between parasite-derived proteins expressed on the surface of infected RBCs and a number of host molecules on the surface of endothelial cells, placental cells and uninfected RBCs. Some receptors for parasite adhesion have been implicated in particular malaria syndromes, such as intercellular adhesion molecule 1 in cerebral malaria and chondroitin sulfate A and hyaluronic acid in placental infection. The principal parasite ligand and antigen on the RBC surface, P falciparum erythrocyte membrane protein 1 encoded by a multigene family termed var, is clonally variant, enabling evasion of specific immune responses. An understanding of these host-parasite interactions in the context of clinical disease and immunity may reveal potential targets to prevent or treat severe forms of malaria.


Altered plasma free amino acid levels in obese traumatized man.
Obesity is a major nutritional disorder that produces many abnormal metabolic responses. The effect of injury-induced stresses acting synergistically with the state of excessive body fat is not well known. Plasma levels of circulating free amino acids reflect the net status of protein breakdown and utilization. Hypoaminoacidemia is a common finding in severe injury and its significance in obese subjects was investigated. We measured in 10 obese (body mass index [BMI] greater than 30) and 10 non-obese (BMI less than 30) traumatized (Injury Severity Score [ISS] 17 to 50) patients, the plasma levels of free amino acids in the early "flow" phase of injury when subjects were receiving maintenance fluids without calories or nitrogen. Postabsorptive control samples were obtained from 10 obese and 10 non-obese volunteers. Obese controls showed an increase in valine, leucine, isoleucine, and glutamic acid levels, and a decrease in glycine, tryptophan, threonine, histidine, taurine, citrulline, and cystine levels compared with lean controls. Hypoaminoacidemia was equally seen in traumatized obese and non-obese patients, and it was mainly due to a 24% decrease in nonessential amino acids. Remarkably, essential amino acid levels were the same in all groups. Arginine and ornithine levels were significantly different in traumatized obese compared with non-obese patients. The hypoglycinemia seen in non-obese trauma patients was absent in obese patients. The changes in levels of sulphur-containing amino acids also suggest that monitoring of these levels should be included in the nutritional management of obese trauma patients.


Kinetic studies on the mechanism of chorismate mutase/prephenate dehydratase from Escherichia coli K12.
The effect of pH on chorismate mutase/prephenate dehydratase (chorismate pyruvate mutase/prephenate hydro-lyase (decarboxylating) EC 184.108.40.206/EC 126.96.36.199) from Escherichia coli K12 has been studied. While the maximum velocity of both activities is independent of pH, Km for chorismate or prephenate shows a complex pH dependence. Differences in mutase activity in acetate/phosphate/borate and citrate/phosphate/borate buffers were traced to inhibition by citrate. When a variety of analogues of citrate were tested as possible inhibitors of the enzyme, several were found to inhibit mutase and dehydratase activities to different extents, and by different mechanisms. Thus citrate competitively inhibits mutase activity, but inhibits dehydratase activity by either a non-competitive or an uncompetitive mechanism. Conversely, cis- and trans-aconitate competitively inhibit dehydratase activity, but are partially competitive inhibitors of mutase activity. The differential effects of these inhibitors on the two activities are consistent with the existence of two distinct active sites, but additionally suggest some degree of interconnection between them. The implications of these results for possible mechanisms of catalysis by chorismate mutase/prephenate dehydratase are discussed.


Breeding Next-Generation Naturally Colored Cotton.
Use of naturally colored cotton (NCC) in the textile industry is limited due to its inferior fiber quality. Recent advances in understanding pigmentation in NCC fiber and the genetic relationship between pigmentation and fiber development may overcome this hindrance and can guide developing high fiber quality and yield NCC.


Prevalence of Gestational Diabetes Mellitus among pregnant women attending antenatal care clinic of St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia.
The prevalence of Gestational Diabetes Mellitus (GDM) varies worldwide among racial and ethnic groups, population characteristics (eg, average age and body mass index (BMI) of pregnant women), testing method, and diagnostic criteria. This study was aimed at determining the prevalence of GDM using the one-step 75-g Oral glucose tolerance test (OGTT) protocol, with plasma glucose measurement taken when patient is fasting and at 1 and 2 h and identify associated risk factors among pregnant women attending antenatal care clinic at St. Paul Hospital Millennium Medical College (SPHMMC) in Addis Ababa, Ethiopia. Institution based cross sectional study was conducted from April, 2017 to October, 2017 at antenatal care clinic of SPHMMC among a randomly selected sample of 390 eligible pregnant women. Data were collected using a pretested questioner using 5% of the total sample size and later was modified accordingly to capture all the necessary data. Descriptive statistics, independent t-test and Binary Logistic Regression were used for analysis using SPSS version 23.0. The prevalence of GDM among the study population was 16.9%. Factors that affect prevalence of GDM were age group (AOR = 2.75, 95% CI: 1.03, 7.35 for 30-34 years old and AOR = 4.98, 95% CI: 1.703, 14.578 for ≥ 35 years old)and BMI (AOR = 2.23, 95% CI: 1.21, 4.11). The prevalence of GDM among the study population is higher than previous reports in Ethiopia and even in other countries. This implies that these women and their newborns might be exposed to increased risk of immediate and long term complications from GDM including future risk of GDM and Type II Diabetes Mellitus.


Lack of selectivity for ventricular and ischaemic tissue limits the antiarrhythmic actions of lidocaine, quinidine and flecainide against ischaemia-induced arrhythmias.
The antiarrhythmic effectiveness, electrocardiographic and haemodynamic properties of three representative class I antiarrhythmics have been investigated in anaesthetized rats. Quinidine, lidocaine and flecainide were chosen as representatives of class Ia, Ib and Ic, respectively. Lidocaine showed the greatest frequency and 'ischaemia' dependency and a high dose provided complete protection against ischaemic arrhythmias induced by coronary artery occlusion. Flecainide showed the least frequency and ischaemia dependency and the least antiarrhythmic effectiveness. Quinidine was only slightly more effective than flecainide. The three drugs were approximately equi-potent in lowering blood pressure which limited the maximum dose that could be tested. The highest dose of lidocaine also caused convulsions in conscious animals. Thus, while lidocaine had selectivity for ischaemic tissue, and for high frequencies, the central nervous system and cardiovascular toxicity limited its usefulness against ischaemia-induced arrhythmias. Quinidine and flecainide's lack of selectivity for ischaemia, and/or high frequencies, probably accounted for their limited antiarrhythmic actions against ischaemia-induced arrhythmias. This study emphasizes that class I drugs can only provide useful protection against ischaemia-induced arrhythmias if they have marked cardiac selectivity as well as selectivity for ischaemic cardiac tissue.


Replication and pathogenic potential of influenza A virus subtypes H3, H7, and H15 from free-range ducks in Bangladesh in mammals.
Surveillance of wild aquatic birds and free-range domestic ducks in the Tanguar Haor wetlands in Bangladesh has identified influenza virus subtypes H3N6, H7N1, H7N5, H7N9, and H15N9. Molecular characterization of these viruses indicates their contribution to the genesis of new genotypes of H5N1 influenza viruses from clade 22.214.171.124a that are dominant in poultry markets in Bangladesh as well as to the genesis of the highly pathogenic H5N8 virus currently causing disease outbreaks in domestic poultry in Europe and the Middle East. Therefore, we studied the antigenicity, replication, and pathogenicity of influenza viruses isolated from Tanguar Haor in the DBA/2J mouse model. All viruses replicated in the lung without prior mammalian adaptation, and H7N1 and H7N9 viruses caused 100% and 60% mortality, respectively. H7N5 viruses replicated only in the lungs, whereas H7N1 and H7N9 viruses also replicated in the heart, liver, and brain. Replication and transmission studies in mallard ducks showed that H7N1 and H7N9 viruses replicated in ducks without clinical signs of disease and shed at high titers from the cloaca of infected and contact ducks, which could facilitate virus transmission and spread. Our results indicate that H7 avian influenza viruses from free-range ducks can replicate in mammals, cause severe disease, and be efficiently transmitted to contact ducks. Our study highlights the role of free-range ducks in the spread of influenza viruses to other species in live poultry markets and the potential for these viruses to infect and cause disease in mammals.


A facile approach to nanoarchitectured three-dimensional graphene-based Li-Mn-O composite as high-power cathodes for Li-ion batteries.
We report a facile method to prepare a nanoarchitectured lithium manganate/graphene (LMO/G) hybrid as a positive electrode for Li-ion batteries. The Mn(2)O(3)/graphene hybrid is synthesized by exfoliation of graphene sheets and deposition of Mn(2)O(3) in a one-step electrochemical process, which is followed by lithiation in a molten salt reaction. There are several advantages of using the LMO/G as cathodes in Li-ion batteries: (1) the LMO/G electrode shows high specific capacities at high gravimetric current densities with excellent cycling stability, e.g., 84 mAh·g(-1) during the 500th cycle at a discharge current density of 5625 mA·g(-1) (~38.01 C capacity rating) in the voltage window of 3-4.5 V; (2) the LMO/G hybrid can buffer the Jahn-Teller effect, which depicts excellent Li storage properties at high current densities within a wider voltage window of 2-4.5 V, e.g., 93 mAh·g(-1) during the 300th cycle at a discharge current density of 5625 mA·g(-1) (~38.01 C). The wider operation voltage window can lead to increased theoretical capacity, e.g., 148 mAh·g(-1) between 3 and 4.5 V and 296 mAh·g(-1) between 2 and 4.5 V; (3) more importantly, it is found that the attachment of LMO onto graphene can help to reduce the dissolution of Mn(2+) into the electrolyte, as indicated by the inductively coupled plasma (ICP) measurements, and which is mainly attributed to the large specific surface area of the graphene sheets.


Nucleotide sequence of a putative periplasmic Mn superoxide dismutase from Acinetobacter calcoaceticus ADP1.
We determined 5.8 kilobases of nucleotide sequence upstream of the rubredoxin encoding rubA gene of Acinetobacter calcoaceticus (Ac) ADP1. Sequence analysis revealed four open reading frames named cysD', cobQ, sodA and lysS, coding for proteins with high similarity to known sulfate adenylate transferases (partial), cobyric acid synthases, superoxide dismutases (Sod) and lysyl tRNA synthetases, respectively. Out of a large number of bacterial Sod sequences SodA of Ac ADP1 is the first member of the Fe/Mn Sod family apparently located in the periplasmic space.


In vitro susceptibility of Pasteurella multocida subspecies multocida strains isolated from swine to 42 antimicrobial agents.
The minimal inhibitory concentrations (MICs) of 42 antimicrobial agents were determined against 59 strains of Pasteurella multocida subspecies multocida, all isolated from swine lungs with lesions indicative of pneumonia. Penicillins (except cloxacillin), aminoglycosides, tetracyclines, erythromycin, josamycin, thiamphenicol, colistin, rifampin and mupirocin showed good activities, with ranging resistance between 0 and 6.8%. Higher resistance was observed for spiramycin and fosfomycin. Tylosin, vancomycin, metronidazole, dapsone and tiamulin, to which strains showed high rates of resistance, were ineffective. Cephalosporins (especially the third-generation cephalosporins) and quinolones (especially the fluorinated quinolones) were the most effective antimicrobial agents against P. multocida subsp. multocida strains and they might be of value for in vivo use.


A Pregnant Woman with Spina Bifida: Need for a Multidisciplinary Labor Plan.
Women with spina bifida present both obstetrical and anesthesia challenges. They are more likely to require a caesarian delivery and traditionally neuraxial anesthesia has been avoided due to concerns of worsening neurologic disability. The case of a pregnant woman with a history of a surgically corrected lipomeningocele and tethered cord is presented to illustrate the need for a comprehensive labor plan.


Welsh dental trainees' confidence and competence in completing orthodontic assessments and referrals.
To improve the confidence and competence of newly qualified dentists in Wales in undertaking orthodontic assessments and making orthodontic referrals. Quality improvement project. Study days arranged by the Wales Deanery. The 2018-2019 cohort of dental foundation trainees (DFTs) and dental core trainees (DCTs) in Wales. Data were collected prospectively between January and February 2019 utilising a 20-item questionnaire based around knowledge and clinical ability in orthodontic assessment and referrals (Stage 1). In May 2019, the trainees were provided with an e-learning package tailored to the results of the clinical questions and the feedback received in Stage 1. After this, trainees repeated the questionnaire with a simplified Index of Orthodontic Treatment Need (IOTN; Stage 2). There was increased self-reported confidence in 'conducting orthodontic assessments' from 67% to 95% and 'competence in completing orthodontic referrals' from 81% to 92%. At baseline, this cohort were only able to correctly determine dental age and orthodontic treatment need for 40.7% (mean) of the presented linical cases. Following the teaching intervention, this was improved with an average of 70.9% of clinical cases answered correctly. Despite the noted improvement in the self-reported confidence and competence in undertaking orthodontic assessments and referrals in this cohort, there is still room for improvement. Hands-on orthodontic experience during dental training improved the self-reported confidence and competence with assessments and referrals. The results of this quality improvement project emphasise the need for regular continuing professional development in the field of orthodontics to maintain competence in utilising IOTN and referring appropriately.


The photocatalytic rate of ZnO supported onto natural zeolite nanoparticles in the photodegradation of an aromatic amine.
Aniline and its derivate are critical environmental pollutants, and thus, the introduction of an eco-friendly catalyst for removing them is an important research future. The ZnO supported on the ball-mill prepared clinoptilolite nanoparticles (CNPs) was prepared via an ion-exchange process followed by the calcination process. The amount of loaded ZnO in the ZnO-CNP (CZ) samples varied as 0.54, 0.63, 0.72, and 0.86 meq/g as the Zn(II) concentration in the ion-exchange solution varied from 0.1 to 0.5 M. The ZnO-CNP catalyst was briefly characterized by XRD, FTIR, and DRS techniques. The pHpzc value for the various ZnO-CNPs was about 7.1 that had no change with the ZnO loading. By applying the Scherrer equation on the XRD results, a nano-dimension of about 50 nm was obtained for the catalyst. Bandgap energy of the ZnO-CNP samples was estimated by applying the Kubelka-Munk equation on the DRS reflectance spectra. The value for the CZ2 catalyst was about 3.64 eV. The supported ZnO-CNP sample was then used in the photodegradation of 2,4-dichloroaniline (DCA). Raw zeolite showed a relatively low photocatalytic activity. The degradation efficiency was followed by recording the absorbance of the DCA solution by UV-Vis spectrophotometer. The effects of the essential critical operating factors on the degradation efficiency were kinetically studied by applying the Hinshelwood equation to the results. The ZnO-CNP catalyst with 2 w% ZnO showed the best photocatalytic rate in the optimal conditions of 0.75 g/L, CDCA: 15 ppm, and the initial pH: 5.8. Finally, HPLC analysis of the blank and the photodegraded DCA solutions at 180 and 300 min confirmed 74 and 87% of DCA molecules were degraded during these times. The results confirm that supported ZnO onto clinoptilolite caused enhanced photocatalytic activity because the zeolite internal electrical field prevents the e-/h+ recombination.


Internal medicine patients admitted without COVID-19 during the outbreak.
The first case of COVID-19 in Israel was reported on February 21, 2020. Shaare Zedek (SZ), a 1000-bed tertiary care medical centre in Jerusalem, Israel, cared for a significant number of these patients. While attention focused on COVID-19 patients, uninfected patients were admitted to decreasing numbers of available internal medicine (IM) beds as IM departments were converted to COVID-19 isolation wards. As a result of the increase in COVID-19 patients, closure of IM wards, re-assignment of staff and dynamic changes in available community placement options, we investigated the impact of the outbreak on IM patient not admitted for COVID-19. We reviewed IM admissions during March 15-April 30, 2020 for patients without COVID-19. Characteristics assessed included number of admissions, age, length of stay, mortality rate, number of discharges, number discharged home and functional status of the patients. Data were compared with the previous 3 years (2017-2019) during the same time period. During March 15-April 30, 2020 there were 409 patients admitted to IM compared with a mean of 557 over the previous 3 years. Fewer patients were admitted to the ED and the IM wards during the outbreak. There was no significant difference between the two groups with regards to gender, in-hospital mortality rate, number discharged, number discharged home and patient functional level. Patients admitted during the outbreak to IM were younger (74.85 vs 76.86 years) and had a mean shorter hospital length of stay (5.12 vs 7.63 days) compared with the previous 3 years. While the characteristics of patients admitted to IM during the outbreak were similar, hospital length of stay was significantly shorter. Internal management processes, as well as patient preferences may have contributed to this observation. An infectious disease outbreak may have a significant effect on uninfected admitted patients.


Unraveling the interaction of hydroxylamine and Fe(III) in Fe(II)/Persulfate system: A kinetic and simulating study.
Hydroxylamine showed an outstanding performance on enhancing the oxidation of pollutants in Fe(II) involved advanced oxidation processes, while the detailed reaction schemes have not been fully revealed. Specific functions of hydroxylamine in the oxidation of benzoic acid with Fe(II)/persulfate (PDS) system were explored. With the addition of hydroxylamine, degradation kinetics of benzoic acid deviated from both two-stage kinetics and pseudo first order kinetics, but could be interpreted well with binomial regression analysis. Degradation rate constant (kobs) of benzoic acid was calculated and showed the same variation trend with [hydroxylamine][Fe(III)]2/([Fe(II)][H+])2, the value of which was changed during reaction processes. A detailed kinetic model for simulating the degradation profile of benzoic acid with hydroxylamine acceleration was proposed for the first time and indicated that interactions of hydroxylamine and Fe(III) were fast equilibrium reactions, which was a dominant factor influencing the oxidation kinetics of benzoic acid in Fe(II)/hydroxylamine/PDS system. Comparative study showed that when 1.4 mM of ascorbic acid was added into Fe(II)/PDS system, degradation kinetics of benzoic acid was similar to that enhanced by hydroxylamine. However, when 0.6 mM or 1.0 mM of ascorbic acid was added, oxidation kinetics still presented as the two-stage profile. Kinetic simulations indicated that Fe(II) was produced slower from Fe(III)-ascorbic acid complexes than that with hydroxylamine, which caused the difference in oxidation kinetics. This study could improve our understanding about the effect of hydroxylamine and other reductants in promoting pollutants elimination in Fe(II)/PDS system.


Hypoxia Enhances Immunosuppression by Inhibiting CD4+ Effector T Cell Function and Promoting Treg Activity.
Hypoxia occurs in many pathological conditions, including inflammation and cancer. Within this context, hypoxia was shown to inhibit but also to promote T cell responses. Due to this controversial function, we aimed to explore whether an insufficient anti-tumour response during colitis-associated colon cancer could be ascribed to a hypoxic microenvironment. Colitis-associated colon cancer was induced in wildtype mice, and hypoxia as well as T cell immunity were analysed in the colonic tumour tissues. In addition, CD4+ effector T cells and regulatory T cells were cultured under normoxic and hypoxic conditions and examined regarding their phenotype and function. We observed severe hypoxia in the colon of mice suffering from colitis-associated colon cancer that was accompanied by a reduced differentiation of CD4+ effector T cells and an enhanced number and suppressive activity of regulatory T cells. Complementary ex vivo and in vitro studies revealed that T cell stimulation under hypoxic conditions inhibited the differentiation, proliferation and IFN-γ production of TH1 cells and enhanced the suppressive capacity of regulatory T cells. Moreover, we identified an active role for HIF-1α in the modulation of CD4+ T cell functions under hypoxic conditions. Our data indicate that oxygen availability can function as a local modulator of CD4+ T cell responses and thus influences tumour immune surveillance in inflammation-associated colon cancer.


Effects of bifunctional linker on the optical properties of ZnO nanocolumn-linker-CdSe quantum dots heterostructure.
We study the effects of bifunctional linker on the optical properties of ZnO nanocolumn-linker-CdSe quantum dots heterostructure. The CdSe quantum dots are anchored on the surface of ZnO nanocolumns through either aliphatic linker of 3-aminopropyl trimethoxysilane (APS) or aromatic linker of p-aminophenyl trimethoxysilane (APhS). X-ray photoelectron spectroscopy is used to confirm the bifunctional linker bound onto CdSe quantum dots and onto the ZnO nanocolumns. The TEM study reveals a CdSe quantum dot shell of about 15 nm coated on the ZnO nanocolumns. The photoluminance (PL) spectroscopy and time-resolved PL spectroscopy of ZnO nanocolumn-linker-CdSe quantum dots reflects that the photo-induced electron transfer across the interface of ZnO and CdSe through the aromatic APhS is more efficient than the aliphatic APS. This study demonstrates that through the usage of appropriate surface linker, the charge transfer rate across the interfaces of donor/acceptor (D/A) heterostructure can be improved for potential photovoltaic cell applications.


Mutational analysis of the RNase-like domain in subunit 2 of fission yeast RNA polymerase II.
Local sequence similarity exists between the subunit 2 of eukaryotic RNA polymerases II and the barnase-type bacterial RNases. The RNase-like domain from the Rpb2 of Schizosaccharomyces pombe was expressed in Escherichia coli as a GST fusion protein and examined for its RNase activity. When the GST fusion protein was incubated in vitro with 32P-labeled RNA, the RNA degradation activity was less than 0.1%, if any, of the level of synthetic barnase. In order to check the in vivo function of this region, we constructed two mutant rpb2 alleles, rpb2E357A and rpb2H386L, each carrying a single amino acid substitution at the site corresponding to one of the three essential amino acid residues forming the catalytic site in barnase (mutation of barnase at the corresponding sites results in complete loss of RNase activity) and five other mutant rpb2 alleles, each carrying a single mutation at various positions within the RNase-like domain but outside the putative catalytic site for RNase activity. When these mutant rpb2 alleles were expressed in an rpb2-disrupted S. pombe strain, all the mutants grew as well as the wild-type parent and did not show any clear defective phenotypes. These results suggest either that the RNase-like domain in Rpb2 does not function as an RNase in vivo or that the RNase activity of this domain, if present at all, is not essential for cell growth.


Distribution and specific central projections of mechanoreceptors in the thorax and proximal leg joints of locusts. II. The external mechanoreceptors: hair plates and tactile hairs.
Tactile hairs on the locust thorax can be divided into two classes by their external morphology and their central projection pattern: Short hairs, 10--100 micrometer in length, which are assembled in distinct plates and rows, and long hairs, 100--800 micrometer in length, which are distributed all over the body and are organized in large fields or aligned along the ridges of the appendages. The sensory fibers of the first class arborize in the lateral dorsal neuropile of thoracic ganglia and then extend further into the ipsilateral half of the corresponding ganglion in three main bundles from which fine rami of fibers end in the intermediate neuropile. In all three thoracic ganglia the projection pattern of homologous hair plates is similar. The sensory fibers of the second class exclusively terminate in special median ventral neuropiles, the ventral association center (VAC) and ventralmost ventral association center (VVAC). In addition fibers from meso- and metathoracic hairs, located close to the longitudinal midline of the animal, may terminate in the contralateral VAC and with one branch project to the next anterior ganglion through the ipsilateral connective. In contrast, fibers from prothoracic hairs were not found to leave their ganglion.


Sodium valproate: serial monitoring of EEG and serum levels.
The clinical and electroencephalographic (EEG) effects of sodium valproate were studied in four patients by means of serial 24-hour EEG recordings and simultaneous hourly determinations of serum drug concentrations. The patients all had frequent clinical seizures and generalized spike-wave discharges. Valproate appeared to reduce diurnal paroxysmal discharges (PD) and clinical seizures, but the effect on nocturnal PD was less marked. The extent and duration of the depression of PD and seizures varied. Altering the distribution of the total daily dose may change the pattern of clinical seizures and PD. Valproate concentrations fluctuated widely over 24 hours, and the significance of single estimations often cited in the literature appears dubious. Peak serum concentrations above 100 micrograms per milliliter may be necessary in some patients to achieve clinical and EEG improvement.


Two-Stage Residual Inclusion Estimation in Health Services Research and Health Economics.
Empirical analyses in health services research and health economics often require implementation of nonlinear models whose regressors include one or more endogenous variables-regressors that are correlated with the unobserved random component of the model. In such cases, implementation of conventional regression methods that ignore endogeneity will likely produce results that are biased and not causally interpretable. Terza et al. (2008) discuss a relatively simple estimation method that avoids endogeneity bias and is applicable in a wide variety of nonlinear regression contexts. They call this method two-stage residual inclusion (2SRI). In the present paper, I offer a 2SRI how-to guide for practitioners and a step-by-step protocol that can be implemented with any of the popular statistical or econometric software packages. We introduce the protocol and its Stata implementation in the context of a real data example. Implementation of 2SRI for a very broad class of nonlinear models is then discussed. Additional examples are given. We analyze cigarette smoking as a determinant of infant birthweight using data from Mullahy (1997). It is hoped that the discussion will serve as a practical guide to implementation of the 2SRI protocol for applied researchers.


The effects of a protease inhibitor fraction from tepary bean (Phaseolus acutifolius) on in vitro cell proliferation and cell adhesion of transformed cells.
Some protease inhibitors (PI), such as the soybean Bowman-Birk protease inhibitor (SBBI), have been described as anticarcinogenic agents. Although PI are ubiquitous compounds in living organisms, the anticarcinogenic potential of PIs other than SBBI remain poorly explored. We evaluated the antiproliferative effect of a protein fraction from tepary bean (Phaseolus acutifolius) seeds with protease inhibitor activity (TPIF), on normal and on malignant cells. TPIF was obtained after precipitation with ammonium sulfate and gel filtration, and its bioactivity was assayed in vitro on HeLa cells, normal 3T3 fibroblasts and 3T3/v-mos transformed fibroblasts. TPIF showed antiproliferative and cytotoxic effects on 3T3/v-mos transformed fibroblasts in a dose-dependent way. On the contrary, TPIF was only cytostatic for normal 3T3 cells at the highest doses assayed, and had no effect on epithelial HeLa cells proliferation. Sublethal TPIF doses also stimulated cell adhesion of poorly adherent 3T3/v-mos cell line.


Imbalance of Clara cell-mediated homeostatic inflammation is involved in lung metastasis.
We have previously shown that tumor necrosis factor (TNF)α produced from primary tumor-induced expression of two endogenous Toll-like receptor 4 (TLR4) ligands, S100A8 and serum amyloid A3 (SAA3), in pre-metastatic lungs. However, mechanistic details of the signaling network and relevance to pulmonary physiology are poorly understood. Here, we identify Clara cells as a control tower of the network. Clara cell ablation by naphthalene suppressed pulmonary recruitment of CD11b+TLR4+ cells and spontaneous lung metastasis. Clara cells turned out to express TLR4 through which SAA3 was auto-amplified. Reciprocal bone marrow transplantation between wild-type and TLR4 knockout mice demonstrated that pulmonary TLR4+ Clara cells could be derived from bone marrow. SAA3-induced TNFα expression in both alveolar type II cells and macrophages. Primary co-cultures of alveolar type II cells and Clara cells revealed that the induction of TNFα in alveolar type II cells was dependent on the Clara cell-mediated amplification of SAA3. SAA3 induction by bacterial endotoxin also required both Clara cells and TLR4. Thus, pulmonary metastatic soil may feature deregulation of homeostatic inflammatory responses to constant assaults of microbes with endotoxin.


[Watch out for headaches at the end of a pregnancy! Do not miss an autoimmune hypositys].
We report the case of a 21-year-old pregnant women (36 WA) presenting intensive headaches and visual disturbances. Those sellar compression symptoms have made us suppose the diagnosis of autoimmune hypophysitis. MRI has confirmed the typical aspect of symmetric enlargement of the pituitary gland with a strong and homogenous enhancement after gadolinium. This pathology associated to a high morbidity and mortality due to partial or complete deficit of the anterior pituitary hormones, shall be reminded more often.


Comparison of DNA and RNA synthesis in dorsal and ventral frog embryo ectoderm during gastrulation.
A comparison of the rates of DNA and RNA synthesis of the dorsal gastrula ectoderm being induced to form neural tissue with the uninduced ventral ectoderm has been made for developing embryos ofRana pipiens. There was a higher rate of DNA synthesis per cell in the dorsal ectoderm, but the rates of RNA synthesis per cell in the induced and uninduced ectoderm were similar. The rate of RNA synthesis based on an equivalent amount of total protein was greater for the induced than for the unindueed ectoderm. This is ascribed to the presence of more cells in the induced ectoderm and this is substantiated by the higher DNA/protein ratio for the induced than for the uninduced ectoderm.


Gain control by sparse, ultra-slow glycinergic synapses.
In the retina, ON starburst amacrine cells (SACs) play a crucial role in the direction-selective circuit, but the sources of inhibition that shape their response properties remain unclear. Previous studies demonstrate that ∼95% of their inhibitory synapses are GABAergic, yet we find that the light-evoked inhibitory currents measured in SACs are predominantly glycinergic. Glycinergic inhibition is extremely slow, relying on non-canonical glycine receptors containing α4 subunits, and is driven by both the ON and OFF retinal pathways. These attributes enable glycine inputs to summate and effectively control the output gain of SACs, expanding the range over which they compute direction. Serial electron microscopic reconstructions reveal three specific types of ON and OFF narrow-field amacrine cells as the presumptive sources of glycinergic inhibition. Together, these results establish an unexpected role for specific glycinergic amacrine cells in the retinal computation of stimulus direction by SACs.


Effect of a nonavalent conjugate vaccine on carriage of antibiotic-resistant Streptococcus pneumoniae in day-care centers.
In the developed societies, day-care centers (DCCs) play an important role in the spread of antibiotic-resistant pneumococci both within the facility and from the facility to the community. This study was conducted to determine the effect of a nonavalent pneumococcal conjugate vaccine (PCV-9) on the carriage of antibiotic-resistant pneumococci in the DCC. Healthy DCC attendees ages 12 to 35 months were randomized to receive either PCV-9 or a control vaccine (conjugate meningococcus C vaccine) in a double blinded manner. Nasopharyngeal Streptococcus pneumoniae cultures were obtained from each subject before vaccination, monthly during the first year of follow-up and every 2 to 3 months during the second year of follow-up. For each isolate the serotype and antibiotic susceptibility were determined. A total of 132 and 130 evaluable toddlers received either PCV-9 or the control vaccine, respectively. In total 3748 cultures were obtained, of which 2450 (65%) were positive for S. pneumoniae. The resistance rates to penicillin, trimethoprim-sulfamethoxazole and erythromycin were 36, 35 and 16%, respectively. Resistance rates to > or =1 and > or =3 antibiotic categories were 52 and 9%, respectively. Antibiotic resistance was found mainly in the 5 serotypes included in the pneumococcal conjugate vaccines (6B, 9V, 14, 19F and 23F) and in 2 related serotypes (6A and 19A). In the vaccinated group a clear and significant reduction of the carriage rate of the serotypes included in the vaccine and the related serotype 6A as well as an increase in the carriage rate of the serotypes not included in the vaccine were observed. In parallel a significant decrease in carriage rate of antibiotic-resistant pneumococci was observed. The reduction of carriage of antibiotic-resistant pneumococci was seen in all age windows but was greater in the age window <36 months. The carriage rate of antibiotic-resistant S. pneumoniae, including multiply resistant S. pneumoniae, in DCC attendees is high. Pneumococcal conjugate vaccines seem to be an important tool for reducing the carriage rate of antibiotic-resistant pneumonia in DCCs.


General Dentists' Perceptions About Their Relationship With Specialists.
This paper assesses the nature of the general dentist-specialist relationship, as perceived by general dentists in Canada. A cross-sectional web-based survey was administered to general dentists across Canada who are part of the Canadian Dental Association register and who have consented to receiving email surveys (N ≈ 11,300). Information including sociodemographic and practitioner- and practice-related factors was collected using a 47-item questionnaire. The general dentist-specialist relationship was conceptualised on the basis of 4 factors: communication, confidence, competition, and referrals. Descriptive analysis was conducted. The response rate for the survey was 11.7% (n = 1328). Most general dentists specified that specialists sent timely information/reports (93%), were partners in delivering care (64%), presented little competitive pressure (87%), and were strongly collegial (85%). In general, the study demonstrated that Canadian general dentists held a positive perception of their relationship with the specialists.


Downregulation of circular RNA circ-LDLRAD3 suppresses pancreatic cancer progression through miR-137-3p/PTN axis.
Emerging evidence suggests that dysregulation of circular RNAs (circRNAs) closely associated with cancer progression. In this paper, we focus on exploring the functional role of circ-LDLRAD3 in pancreatic cancer. Gene expression was determined using quantitative reverse transcriptase polymerase chain reaction and Western blot. Cell count kit-8 and 5-ethynyl-2'-deoxyuridine assay were applied to evaluate the proliferation of PANC-1 and SW1990 cells. The migration and invasion of PANC-1 and SW1990 cells were assessed using wound healing assay and transwell invasion assay. Luciferase reporter assay was performed for target validation. The results showed that circ-LDLRAD3 was overexpressed in pancreatic cancer tissues and cell lines. Increased expression of circ-LDLRAD3 was indicative of a poor prognosis in patients with pancreatic cancer. Knockdown of circ-LDLRAD3 repressed the growth of pancreatic cancer in vitro and in vivo. miR-137-3p was identified as a direct target of circ-LDLRAD3. More importantly, upregulation of circ-LDLRAD3 could mitigate the inhibitory effect of miR-137-3p on the proliferation, migration and invasion of pancreatic cancer cells. Besides, circ-LDLRAD3 could regulate the expression of pleiotrophin (PTN) through miR-137-3p. Taken together, knockdown of circ-LDLRAD3 repressed the proliferation, migration and invasion of pancreatic cancer cells through miR-137-3p/PTN axis, providing a new mechanism for pancreatic cancer progression.


High-performance and environmentally stable planar heterojunction perovskite solar cells based on a solution-processed copper-doped nickel oxide hole-transporting layer.
An effective approach to significantly increase the electrical conductivity of a NiOx hole-transporting layer (HTL) to achieve high-efficiency planar heterojunction perovskite solar cells is demonstrated. Perovskite solar cells based on using Cu-doped NiOx HTL show a remarkably improved power conversion efficiency up to 15.40% due to the improved electrical conductivity and enhanced perovskite film quality. General applicability of Cu-doped NiOx to larger bandgap perovskites is also demonstrated in this study.


Serum anti-Müllerian hormone levels are not associated with aneuploidy rates in human blastocysts.
Anti-Müllerian hormone (AMH) is the most established biomarker for estimating ovarian reserve. No reliable marker of oocyte quality, however, is available. Is there an association between the rates of aneuploidy and the different ranges of serum AMH levels? Retrospective, single-centre study of 1718 patients undergoing intracytoplasmic sperm injection and preimplantation genetic testing with aneuploidy at the blastocyst stage between January 2015 and December 2019. Patients were stratified into six different categories of AMH (ng/ml) according to percentile distribution. Although a higher number of biopsied embryos were found for higher AMH levels (P = 0.017), a lower rate of biopsied blastocysts per metaphase II (P = 0.019) and per fertilized oocyte (0.023) was observed in this group of high AMH. A higher number of euploid embryos was found for higher AMH values (P = 0.031); however, the rate of aneuploid embryos per metaphase II or per fertilized oocyte was not significantly different across the six groups. No differences were observed in the implantation, pregnancy and ongoing pregnancy rate, or in the miscarriage and biochemical loss rate. Regression analysis did not show any significant correlation between AMH and aneuploid embryos. In this large series of patients, AMH was not related to embryo aneuploidy.


Lipid composition and cholesterol esterification in serum lipoprotein fraction of the horse, Equus caballus.
1. Changes in lipid components of lipoproteins during incubation of horse serum at 37 degrees C were investigated. In non-incubated serum, cholesterol and lecithin existed predominantly in alpha-lipoprotein or in high-density lipoprotein (HDL). Lysolecithin was mainly associated with the fraction with density above 1.21. 2. When serum was separated into alpha- and beta-lipoproteins by the heparin precipitation method after 1 hr incubation, the decrease in alpha-lipoprotein free cholesterol and lecithin was about four times that in beta-lipoprotein counterparts. 3. When serum lipoproteins were separated by ultracentrifugation, the decrease in each lipoprotein free cholesterol was closely paralleled with that in lecithin. 4. HDL appeared to be a preferential substrate for the lecithin: cholesterol acyltransferase reaction. 5. Disc electrophoretic patterns indicated significant differences in the composition of horse serum lipoproteins from those of human and rat.


[The spread of melanoblasts in embryos of different coloured fowls].
The first melanoblasts are found in the embryos of the black Rheinländer and Plymouth Rock chickens at the fifth day of development in the occipital and lumbal region. The further spread of the pigment cells is equal in both races. But at the eight day the pigmented area is much more extended in the Plymouth Rocks. These embryos possess at this time more than twice the amount of melanoblasts which are more pigmented than in Rheinländer embryos of the same age. During the further development this differences are equalized.In both races the colour pattern of the chickens are different and have no similarities with the pattern of adult animals. The different patterns of chickens may be explained by time-dependent, genetic differences during the differentiation of the melanoblasts. The colouration in the adult fowls must be due to different genetic factors, which become effective during the development of the juvenile feathers.


Dependence of Mini-Nutritional Assessment scores with age and some hematological variables in elderly institutionalized patients.
Nutritional imbalance is a serious problem in developing countries, especially for the older population, which makes simple and rapid instruments for nutritional evaluation very necessary in order to have a detailed picture of the undernutrition epidemiology in those places. This work aimed to evaluate the nutritional status of elderly institutionalized patients by use of the Mini-Nutritional Assessment (MNA) test and compare the MNA scores with some hematological variables. We performed a cross-sectional study in elderly institutionalized patients (153) of all nursing homes in the Brazilian city of Uberlândia, using the MNA questionnaire and quantitative analysis of erythrocytes, hematocrit, hemoglobin, serum iron and transferrin. The subjects were classified by gender, nutritional state and age range. The nutritional categories were compared by analysis of variance and the dependence between the considered variables was tested with the Spearman correlation analysis. 60% of the subjects were female. The average age was 74.6 +/- 9.5 and 78.5 +/- 9.5 years for male and female individuals, respectively. 18.3% of the patients presented undernutrition, 45.7% presented risk of undernutrition, and 36.0% were well nourished. These three nutritional categories showed statistically significant differences among the MNA scores, age and all the hematological parameters, for the sum of both genders, but not for the age, iron and transferrin values of the male individuals and hematocrit and hemoglobin values of the female patients. Significant differences between genders were not observed only for the MNA and transferrin values. MNA values presented positive correlations with erythrocytes, hematocrit, hemoglobin, and serum iron levels, and also a negative correlation with age, which was attributed to a worsening of the nutritional state with age. Based on the MNA, 64% of the elderly institutionalized patients of Uberlândia presented risk of undernutrition and undernutrition, and their nutritional state is aggravating with the age increase, which is consistent with the age-dependent decrease observed in some hematological variables. Since the low MNA scores were not necessarily associated to subnormal mean values of the hematological variables, we can conclude that the low MNA values are predicting situations that still did not manifest pathologically in those variables.


Characterisation of carbonic anhydrases from tissues of the cat.
1. Red blood cells from several members of the cat family have been found to contain only carbonic anhydrase (EC 22.214.171.124) isozymes of the "high activity" (carbonic anhydrase II class) in red blood cells. 2. Two carbonic anhydrase II type isozymes have been isolated from red cells of the domestic cat. Kinetic and structural characterisation shows that the two isozymes have identical composition except for a probable difference of one amide group. The general characteristics of cat red cell carbonic anhydrase are similar to other mammalian carbonic anhydrase II isozymes, in particular the dog carbonic anhydrase II. 3. A carbonic anhydrase I (low activity) isozyme has been isolated and characterised from cat caecal mucosa. This carbonic anhydrase I is similar to the carbonic anhydrase I extracted from canine red cells. Comparative studies showed that whereas members of the dog family have carbonic anhydrase I and carbonic anhydrase II in red cells the cat family has only a carbonic anhydrase II type isozyme, however, cat liver and spleen homogenates were also found to contain carbonic anhydrase I identical to that found in caecum.


Using expert opinion rounds to develop valid and realistic manipulations for experimental video-vignette research: Results from a study on clinicians' (un)reasonable argumentative support for treatment decisions in neonatal care.
To develop valid and realistic manipulations for video-vignette research using expert opinion rounds, in preparation of an experimental study on clinicians' (un)reasonable argumentative support for treatment decisions in neonatal care. In three rounds, N = 37 participants (parents/clinicians/researchers) provided feedback on four video-vignette scripts and completed listing, ranking, and rating exercises to determine which (un)reasonable arguments clinicians may provide to support treatment decisions. Round 1: participants deemed the scripts realistic. They judged that, on average, clinicians should provide two arguments for a treatment decision. They listed 13-20 reasonable arguments, depending on the script. Round 2: participants ranked the two most salient, reasonable arguments per script. Round 3: participants rated the most plausible, unreasonable arguments from a predefined list. These results guided the design of 12 experimental conditions. Expert opinion rounds are an effective method to develop video-vignettes that are theoretically sound and ecologically realistic and offer a powerful means to include stakeholders in experimental research design. Our study yielded some preliminary insights into what are considered prevalent (un)reasonable arguments for clinicians' treatment plans. We provide hands-on guidelines on involving stakeholders in the design of video-vignette experiments and the development of video-based health communication interventions - both for research and practice.


Classification of human fetal movement.
A study of fetal activity was undertaken as the first step in a series of physiologic fetal movement studies. A simple, safe, noninvasive, clinically applicable method for studying fetal movement with a tocodynamometer is described. Four basic types of fetal movement have been seen and defined in terms of their durations, recorded patterns, and descriptive terminologies for identifying each movement.


A systematic review and meta-analysis of prospective studies on obesity and risk of inflammatory bowel disease.
There are only a few systematic reviews on the association of obesity with risk of inflammatory bowel disease (IBD) to date. The current study was undertaken to systematically review prospective cohort studies on the association between body mass index (BMI) and risk of IBD. It was carried out according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Relevant prospective cohort studies published from 1969 to July 2020 were searched through PubMed, MEDLINE, SCOPUS, EMBASE, and Google Scholar, using suitable keywords. Hazard ratios (HRs) or relative risks (RRs) and 95% confidence intervals (CIs) for IBD or its subtypes across categories of BMI were extracted. The log HRs/RRs, including standard errors, were calculated based on reported HRs or RRs and their 95% CIs, and overall effect size was calculated using a fixed-effects model. All statistical analyses were done using STATA version 14.0 (Stata Corp LP, College Station, TX, USA). Overall, 9 studies were included. Combining findings from 5 studies, a statistically significant 21% lower risk of ulcerative colitis incidence was found in patients with obesity than in those with normal weight (RR, 0.79; 95% CI, 0.68-0.92; I2= 0.0%), but not with risk of ulcerative colitis exacerbation, as found by meta-analysis of 3 studies. Pooling data from 5 studies, no significant differences were seen in the risk of Crohn's disease incidence between patients in the highest range of BMI and those in the normal range. In addition, no significant nonlinear association was found between BMI and risk of Crohn's disease (P=0.94). A significant inverse association was found between obesity and total IBD incidence (RR, 0.76; 95% CI, 0.66-0.88; I2=93.2%), but not between increasing BMI and IBD exacerbation, or between increasing BMI and IBD incidence.


Stepping forward, stepping backward: a movement-related cortical potential study unveils distinctive brain activities.
Human locomotion is the product of complex dynamic systems, which rely on physical capacities as well as cognitive functions. In our daily life, we mostly experience forward walking, but also backward stepping can occur, as in protective stepping. In this work, we investigated the electroencephalographic (EEG) correlates of cognitive processing underpinning step initiation by means of movement-related cortical potentials (MRCPs) analysis and force-plates recordings. Healthy young volunteers (N = 11) performed self-paced forward- and backward-oriented steps on two force platforms, which were synchronized to simultaneous EEG recordings. MRCPs and their source localization analyses were computed. Results demonstrate the involvement of cognitive processing during step preparation and execution, as showed by the prefrontal activity, which was enhanced in backward stepping. Further, the parietal activity was larger in forward than backward stepping, while motor-related regions were involved in both step directions. Thus, the neural timing and sources of forward and backward stepping suggest a functional distinction of these two actions, which undergo different cortical organizations. Backward stepping requires enhanced cognitive control and can be regarded as an avoidance behavior, while forward stepping would be assimilated to an oriented-to-action behavior mainly localized over parietal areas. In conclusion, preparing body locomotion involves high cognitive processing, with step direction showing different cortical organization and functional specialization.


Oxybutynin gel versus nanoemulgel for treating primary palmar hyperhidrosis: A pilot double-blind randomized controlled trial.
Palmar hyperhidrosis or excessive palmar sweating can reduce one's quality of life as it is associated with significant physical and occupational disabilities. We compared the gel and nanoemulgel of oxybutynin in treating these patients. This pilot study was performed as a double-blind controlled randomized clinical trial at Shahid Faghihi Hospital, Shiraz, Iran. In two randomly allocated groups of 15, patients diagnosed with primary palmar hyperhidrosis by an attending dermatologist applied half a fingertip (roughly 0.25 g) of 1% oxybutynin topical gel or 1% oxybutynin nanoemulgel to both palms every 12 h for one month. The Hyperhidrosis Disease Severity Scale (HDSS), Visual Analog Scale (VAS), and Dermatology Life Quality Index (DLQI) were used to assess the patients at the beginning and end of the study. Statistical analysis was performed using SPSS version 25. The groups were similar in terms of age (p = 0.800), sex (p = 0.096), and baseline HDSS, VAS, and DLQI scores. The mean HDSS scores decreased significantly (p = 0.001) over time in patients receiving the gel (3.00 ± 1.00 vs. 2.33 ± 0.61) or nanoemulgel (2.92 ± 0.82 vs. 2.14 ± 0.53), without a significant difference between the groups. The same was true for the VAS and DLQI scores. Three patients in each group experienced transient, self-limited anticholinergic side effects (p = 0.983). Oxybutynin gel and nanoemulgel offer equal safety and similar efficacy in reducing the disease severity and increasing the quality of life of patients with palmar hyperhidrosis.


Idiopathic short stature.
The diagnostic term, idiopathic short stature, has emerged over the past 30 years and refers to children with short stature of unknown etiology. Controversy exists regarding the scope of the diagnosis and options for its treatment. This article reviews origins of the diagnosis idiopathic short stature and current diagnostic criteria, scientific advances in delineating etiologies of idiopathic short stature, management options, and implications of management decisions for child health.


Impact of intravenous nicotine on BOLD signal response to photic stimulation.
Functional magnetic resonance imaging (fMRI) is increasingly being applied in the study of brain effects of nicotine. In addition, because tobacco smoking is common, many subjects studied with fMRI for other reasons may have appreciable levels of nicotine in plasma and brain during scanning. However, there is concern that the vascular effects of nicotine may alter the coupling between blood oxygen level dependent (BOLD) signal and neuronal activity. The objective of this study was to test for evidence of alteration of BOLD signal response of occipital cortex, a region with a relatively low concentration of neuronal nicotine receptors, to photic stimulation during intravenous infusion of nicotine. Nine nicotine dependent healthy smokers were withdrawn from nicotine under controlled conditions and then scanned while receiving photic stimulation and successive intravenous infusions of saline and nicotine. No evidence for an effect of nicotine on BOLD signal response to photic stimulation was detected at the doses studied. This observation suggests that nicotine does not alter the coupling between BOLD signal and neuronal activity in the visual cortex.


Evaluation of post-traumatic anosmia with MRI and chemosensory ERPs.
Magnetic resonance imaging (MRI) and chemosensory event-related potentials (ERPs) are important methods to evaluate olfactory function, but there is lack of study to explore the application of MRI and chemosensory ERPs in the patients with traumatic anosmia. The data of 26 post-traumatic anosmic patients and 21 healthy controls were retrospectively surveyed; olfaction and olfactory pathway of all participants were measured clinically using the T&T olfactometer, the Sniffin' Sticks, chemosensory ERPs and MRI. All patients were anosmic based on complaints and clinical examinations. In five patients, the olfactory bulb volume was significantly lower than control group. In 18 patients, the olfactory sulcus (OS) depth was similar to control group, but all the participants had a deeper right OS (right = 7.79 ± 1.31, left = 7.06 ± 1.44, p < 0.01). Olfactory ERPs (oERPs) could be evoked in 17 patients, but these signals showed longer latencies and lower amplitude than controls in the N1 (latency p < 0.05, amplitude p < 0.01) and P2 (latency p < 0.01, amplitude p < 0.05) waves. Nine traumatic anosmic patients had no identifiable oERPs; most of them had olfactory center injury. Trigeminal ERPs were detected in all anosmic patients and controls; patients had longer latencies for N1 (p < 0.05) and P2 (p < 0.05) waves, while there was no similar change in amplitude. Older subjects had smaller OB volume and OS depth. Closed head injury could induce anosmia; the severity extent, injury site and subsequent consciousness are related to the olfaction. oERP is the gold standard for olfactory subjective examination; MRI could indicate the lesions on the olfactory pathway and reflect the possibility of detectable oERPs.


Calcium Phosphate Ceramics and Synergistic Bioactive Agents for Osteogenesis in Implant Dentistry.
Implant-supported dental prosthetics are widely used in dental practice. Sufficient peri-implant bone tissue is a crucial prerequisite for the long-term success of this treatment, as insufficient peri-implant bone volume hampers dental implant installation and negatively influences dental implant stability. However, due to tooth extraction, bone metabolism diseases, and trauma, bone defects in the jaw are common in patients, particularly in the elderly and those suffering from underlying conditions. If this is the case, the alveolar ridge has to be augmented for reliable implant placement. Various biomaterials, growth factors (GFs) or GF-based products, and trace elements have been tested and used for alveolar ridge augmentation. Among those biomaterials, calcium phosphates (CaPs) are the most popular due to their promising biocompatibility, great osteoconductivity, and distinguishing osteogenesis. Combining CaPs with GFs or trace elements can further favor bone defect repair. This review mainly focuses on applying artificial CaP biomaterials and their combination with bioactive agents to repair bone defects in implant dentistry.


Effect of Prophylactic Aqueous Suppression on Ahmed Glaucoma Valve Surgery Success.
To evaluate the effect of prophylactic aqueous suppressants immediately post-Ahmed glaucoma valve (AGV) surgery on the rate of hypertensive phase and success. Retrospective case-control study of 80 eyes with refractory glaucoma undergoing AGV surgery. Forty eyes in the intervention group (preoperative aqueous suppressants continued postoperatively) and 40 in the control group (all glaucoma drops stopped after surgery and reintroduced as required) were included in this study. Patients were followed for 1 year. Data collected included intraocular pressure (IOP), number of glaucoma medications, and number of eyes requiring further IOP lowering surgery. The frequency of hypertensive phase and 1-year success was compared between the groups. Hypertensive phase occurred in 22.5% of the intervention group compared to 42.5% of the control group; however, this difference was not statistically significant (P = 0.06). Success at 1 year (IOP ≤21 mmHg but ≥5 mmHg and 20% reduction from baseline without additional surgery) was similar in each group: 77.5% in the intervention group and 62.5% in the control group (P = 0.22). However, at 1 year, significantly more eyes in the intervention group had an IOP ≤17 mmHg (95% vs. 80%, P = 0.04). The mean time interval to a second IOP lowering procedure was significantly shorter in the control group (P < 0.005). With prophylactic preoperative aqueous suppressants, more eyes achieved an IOP of ≤17 mmHg. The time interval to repeat the glaucoma procedure was significantly shorter in the control group.


Formation and characterization of three dimensional human hepatocyte cell line spheroids on chitosan matrix for in vitro tissue engineering applications.
Chitosan was used as a matrix to induce three-dimensional spheroids of HepG2 cells. Chitosan films were prepared and used for culturing Hep G2 cells. Attachment kinetics of the cells was studied on the chitosan films. The optimum seeding density of the Hep G2 cells, required for three-dimensional spheroid formation was determined and was found to be 5 x 10(4)/ml. The growth kinetics of Hep G2 cells was studied using (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) (MTT) assay, and morphology of the cells was studied through optical photographs taken at various days of culture. The liver cell functions of the spheroids were determined by measuring albumin and urea secretions. The results obtained from these studies have shown that the culture of Hep G2 cells on chitosan matrix taking appropriate seeding density resulted in the formation of three-dimensional spheroids and exhibited higher amount of albumin and urea synthesis compared to monolayer culture. These miniature "liver tissue like" models can be used for in vitro tissue engineering applications like preliminary evaluation of the toxicity of drugs and chemicals.


Gadolinium-enhanced magnetic resonance angiography of renal transplants.
Our purpose was to investigate three-dimensional (3D) gadolinium-enhanced magnetic resonance angiography (Gd-MRA) in the evaluation of renal transplant arteries. Eleven MR angiography examinations were performed in nine renal transplant patients. Gd-MRA, three-dimensional phase contrast (3D-PC) post-gadolinium, and two-dimensional time-of-flight (2D-TOF) MR angiography were performed and independently reviewed by three vascular radiologists who, for each MR angiography sequence, separately graded occlusive disease in the ipsilateral iliac artery, the transplant artery anastomosis, and the transplant artery itself. The Gd-MRA and 3D-PC data were reviewed as maximum intensity projections (MIP) reconstructed in standard planes, and the 2D-TOF data were interpreted from source images. In addition, a single vascular radiologist prospectively interpreted the Gd-MRA and 3D-PC data together, hereinafter Gd/PC, from MIP reconstructions for each case. In all of these patients either surgical (n = 3) or angiographic studies (n = 8) were performed within 21 days following the MR examination, which served as a reference standard to determine sensitivity and specificity. The sensitivity/specificity for the detection of significant stenosis were as follows: Gd-MRA, 67/88; 3D-PC, 60.3/76.6; 2D-TOF, 47/81; and Gd/PC, 100/100. The kappa statistic (kappa) for interobserver agreement for the grading of stenoses by 2D-TOF, Gd-PC, and Gd-MRA was 0.48, 0.60, and 0.74, respectively. The percentage of all vascular segments seen well enough to grade (cumulative for all three observers) was 94%, 85%, and 79% for Gd-MRA, 3D-PC, and 2D-TOF, respectively. The combination of Gd-MRA and 3D-PC is a promising approach to the evaluation of transplant renal arteries.


Detection of olive oil adulteration with vegetable oils by ultra-performance convergence chromatography-quadrupole time-of-flight mass spectrometry (UPC2-QTOF MS) coupled with multivariate data analysis based on the differences of triacylglycerol compositions.
Three different vegetable oils, including soybean, corn, and sunflower oils, were differentiated from olive oil by using ultra-performance convergence chromatography coupled with quadrupole time-of-flight (UPC2-QTOF MS) and multivariate data analysis based on their differences in triacylglycerol compositions. Then, olive oil was adulterated by adding these three vegetable oils in 1%, 0.75%, and 0.5% (v/v), and the adulterated olive oils were differentiated from the pure olive oils using the similar analytical strategies but different data processing approaches. After that, the representative markers in differentiating the adulterations were selected, and a mathematical model was created to detect the olive oil adulteration based on these specific markers. These results indicated that UPC2-QTOF MS coupled with multivariate data analysis is a sensitive and accurate method in detecting olive oil adulteration, even in 0.5% adulteration level (v/v). This method could be applied in olive oil adulteration detection, and potentially beneficial to the oil industry.


[Cardiovascular protection and mechanisms of actions of aerobic exercise].
It is well established that aerobic exercise exerts beneficial effect on cardiovascular system, but the underlying mechanisms are yet to be elucidated. Recent studies have shown that aerobic exercise ameliorates insulin resistance, inflammation and mitochondrial dysfunction which play important roles in the development of cardiovascular disease. In this review, we discussed the underlying mechanisms of the cardioprotective role of aerobic exercise, especially the latest progress in this field.


Valproic acid radiosensitizes anaplastic thyroid cells through a decrease of the DNA damage repair capacity.
Anaplastic thyroid cancer (ATC) represents a rare lethal human malignancy with poor prognosis. Multimodality treatment, including radiotherapy, is recommended to improve local control and survival. Valproic acid (VA) is a clinically available histone deacetylase inhibitor with a well-documented side effect profile. In this study, we aim to investigate the combined effect of VA with photon irradiation in vitro. Anaplastic thyroid cancer cells (8505c) were used to investigate the radiosensitizing effect of VA. VA sensitized cells to photon irradiation. VA increased radiation-induced apoptosis and radiation-induced DNA damage measured by γH2AX foci induction. Furthermore, VA prolonged γH2AX foci disappearance over time in irradiated cells and decreased the radiation-induced levels of mRNA of key DNA damage repair proteins of the homologous recombination (HR) and the nonhomologous end joining (NHEJ) pathways. VA at a clinically safe dose enhance the radiosensitivity of 8505c cells through an increase in radiation-induced apoptosis and a disruption in the molecular mechanism of HR and NHEJ DNA damage repair pathways.


[Early recurrent miscarriage: Evaluation and management].
To establish recommendations for early recurrent miscarriages (≥3 miscarriages before 14weeks of amenorrhea). Literature review, establishing levels of evidence and recommendations for grades of clinical practice. Women evaluation includes the search for a diabetes (grade A), an antiphospholipid syndrome (APS) (grade A), a thyroid dysfunction (grade A), a hyperprolactinemia (grade B), a vitamin deficiency and a hyperhomocysteinemia (grade C), a uterine abnormality (grade C), an altered ovarian reserve (grade C), and a couple chromosome analysis (grade A). For unexplained early recurrent miscarriages, treatment includes folic acid and progesterone supplementation, and a reinsurance policy in the first quarter (grade C). It is recommended to prescribe the combination of aspirin and low-molecular-weight heparin when APS (grade A), glycemic control in diabetes (grade A), L-Thyroxine in case of hypothyroidism (grade A) or the presence of thyroid antibodies (grade B), bromocriptine if hyperprolactinemia (grade B), a substitution for vitamin deficiency or hyperhomocysteinemia (grade C), sectionning a uterine septum (grade C) and treating an uterine acquired abnormality (grade C). These recommendations should improve the management of couples faced with early recurrent miscarriages.


[Non-cytokine therapeutic targets].
The arrival of anti-TNF-α to the clinic has been the most successful example of translational research. However, clinical experience has shown that these compounds do not induce clinical remission in half of rheumatoid arthritis (RA) patients. Recently, new biological drugs against non-cytokine targets have been available for RA patients. These compounds deplete B cells or interfere with the activation of T cells and have also shown effectiveness in controlling signs, symptoms and structural damage progression in RA. Second generation B-cell depletion therapies are progressing in the pipeline of several pharmaceutical companies. These compounds will likely improve the immunogenicity and formulation of rituximab, but it is improbable that they will improve the remission rate achieved by the anti-TNF-α δρυγσ. Currently, regulation of signal transduction has evolved into an important field of drug research, and small molecule inhibitors for a number of pathways are tested as new anti-inflammatory agents. For rheumatic diseases, specific Jak3 and Syk inhibitors are, so far, the most successful compounds representing a significant advance over p38 mitogen-activated protein kinase (MAPK) inhibitors.


Incisional Hernia Following Laparoscopy: A Survey of the American Association of Gynecologic Laparoscopists
In order to estimate the risk factors and incidence of post-laparoscopy incisional hernias a one-page questionnaire was sent to all individuals on a mailing list purchased from the AAGL. Adequately completed responses were entered into a computer-based data bank for analysis. Of the 11,500 surveys mailed, 3293 were returned of which 3217 (28%) were evaluable. A total of 933 hernias were reported from an estimated 4,385,000 laparoscopic procedures (21 per 100,000). Of these, 167 (17.9%) were reported to have occurred despite fascial closure. Symptoms or hernia-related morbidity occurred in 648 cases (69.5%), with 157 instances (16.8%) of direct involvement of the large or small intestine. Six hundred sixty-five patients (71.3%) underwent subsequent surgical repair. Of the 840 hernias in which the size of the initial fascial defect was noted, 725 (86.3%) occurred in sites where 10 mm or greater ports had been placed. Respondents reported hernia location in 152 cases with the umbilical locale being the most common (75.7%). Lateral hernias comprised 23.7% of these cases and the suprapubic site was involved only once. In conclusion, post-laparoscopy incisional hernias are uncommon, but far from rare. They are most likely to occur when large ports are used and at the umbilical site. Closure as currently practiced is not completely protective. Further methods and/or devices must be developed so as to minimize the risk of hernia formation.


3-Amino-chromanes and Tetrahydroquinolines as Selective 5-HT2B, 5-HT7, or σ1 Receptor Ligands.
The phenethylamine backbone is a privileged substructure found in a wide variety of G protein-coupled receptor (GPCR) ligands. This includes both endogenous neurotransmitters and active pharmaceutical agents. More than 20 structurally unique heterocyclic phenethylamine derivatives were broadly evaluated for GPCR affinity. Selective ligands for the 5-HT2B, 5-HT7, and σ1 receptors were identified, each with low nanomolar binding affinities. The σ1 receptor affinity was supported in a cellular assay that provided evidence for increased cell survival under oxidative stress.


Collaboration Between a School Nurse Task Force and the Local Health Department in Illinois: Development of a COVID-19 Toolkit.
Multidisciplinary collaboration for healthy student outcomes is not a new concept for school nurses nor is working with public health officials in promoting school-community initiatives. The SARS-CoV-2 (COVID-19; severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019) virus further highlighted the need to work together to promote best practice strategies to arm the community with information and guidance to prevent illness. The McHenry County Health Department recognized the expertise school nurses have in school health and formed a voluntary School Nurse Task Force. This collaboration worked to implement requirements for operating a school during a pandemic. The task force adapted those concepts into a toolkit to assist schools to meet health requirements throughout the most significant pandemic in over 100 years.


A case-control study on egg consumption and risk of stroke among Iranian population.
Most available data that linked intake of egg to risk of stroke came from western countries, with conflicting findings. We aimed to examine the association between egg consumption and risk of stroke among Iranian adults. In a hospital-based case-control study, 195 stroke patients, hospitalized in Alzahra University Hospital, were selected as cases and 195 control subjects, from patients hospitalized in other wards with no history of cerebrovascular diseases or neurologic disorders, were recruited. A validated 168-item food frequency questionnaire (FFQ) was used to assess participants' usual dietary intake, including egg consumption, over the previous year. Other required information was gathered by the use of questionnaires. Consumption of eggs was associated with lower odds of stroke, such that after adjustment for potential confounders, those in the highest category of egg intake (>2 eggs/week) were 77% lower odds to have stroke, compared with those with the lowest category of egg intake (<1 egg/week) (OR 0.23; 95% CI 0.11-0.45). Further controlling for body mass index strengthened the association (OR 0.20; 95% CI 0.09-0.41). We found evidence indicating that high intake of eggs (>2 eggs/week) during the past 1 year was associated with a lower risk of stroke. Further prospective studies are required to confirm these findings.


Reduced gut microbiota diversity in patients with congenital generalized lipodystrophy.
Previous studies suggest intestinal dysbiosis is associated with metabolic diseases. However, the causal relationship between them is not fully elucidated. Gut microbiota evaluation of patients with congenital generalized lipodystrophy (CGL), a disease characterized by the absence of subcutaneous adipose tissue, insulin resistance, and diabetes since the first years of life, could provide insights into these relationships. A cross-sectional study was conducted with patients with CGL (n = 17) and healthy individuals (n = 17). The gut microbiome study was performed by sequencing the 16S rRNA gene through High-Throughput Sequencing (BiomeHub Biotechnologies, Brazil). The median age was 20.0 years old, and 64.7% were female. There was no difference between groups in pubertal stage, BMI, ethnicity, origin (rural or urban), delivery, breastfeeding, caloric intake, macronutrient, or fiber consumption. Lipodystrophic patients presented a lower alpha diversity (Richness index: 54.0 versus 67.5; p = 0.008). No differences were observed in the diversity parameters when analyzing the presence of diabetes, its complications, or the CGL subtype. In this study, we demonstrate for the first time a reduced gut microbiota diversity in individuals with CGL. Dysbiosis was present despite dietary treatment and was also observed in young patients. Our findings allow us to speculate that the loss of intestinal microbiota diversity may be due to metabolic abnormalities present since the first years of life in CGL. Longitudinal studies are needed to confirm these findings, clarifying the possible causal link between dysbiosis and insulin resistance in humans.


Identification of changes in sleep across pregnancy and the impact on cardiometabolic health and energy intake in women with obesity.
This prospective, observational study investigated changes in sleep and the effect on energy intake, gestational weight gain, and cardiometabolic health across pregnancy in 52 healthy pregnant women with obesity. Habitual sleep was assessed by wrist-worn actigraphy (time spent in bed; TIB, total sleep time; TST, and sleep efficiency) in early (130-156 weeks) and late (350-366) pregnancy. A change to habitual sleep was defined as change of one-half of the standard deviation of TIB and TST across six consecutive nights from early pregnancy. Energy intake and changes in weight, fasting glucose, insulin, and lipids across pregnancy were compared between women who changed sleep. During early pregnancy, TIB was 9:24 ± 0:08 h and varied by 1:37 ± 0:07 h across the six nights. TST and sleep efficiency significantly declined from early to late pregnancy (7:03 ± 0:08 h to 6:28 ± 0:09 h, p < 0.001) and (76 ± 0.1% to 71 ± 0.2%, p < 0.001), respectively. For women who increased TIB (n = 11), fasting glucose decreased (-11.6 ± 4.3%, p < 0.01) across pregnancy and they had a trend towards decreased insulin (-57.8 ± 33.5%; p = 0.09) and HOMA-IR (-72.4 ± 37.3%; p = 0.06) compared to women who decreased TIB (n = 13). Women who increased TIB had a significantly lower daily energy intake across pregnancy (-540 ± 163 kcal; p < 0.01) and tended to have less gestational weight gain (-147 ± 88 g/week; p = 0.10). Changes in TST did not affect plasma markers, energy intake or weight gain. The positive relationship between sleep and cardiometabolic health during pregnancy is explained in part by lower energy intake. We hypothesize lower energy intake is due to a prolonged overnight fast and a decrease in the time available for eating.


Prominent persisting Eustachian valve initiates spontaneous right-to-left shunt and paradoxical embolism in a patient with patent foramen ovale.
The Eustachian valve (EV) is an embryological remnant of the inferior vena cava valve that prenatally directs the oxygenated blood from inferior vena cava across the patent foramen ovale (PFO) into systemic circulation. We present a 30-year-old man with PFO whose prominent EV initiated spontaneous right-to-left shunt without Valsalva maneuver and promoted paradoxical embolism. Even when the persistence of EV is prominent in adult, it has been considered to be benign finding in the absence of the associated cardiac anomalies. EV should be considered as an adjunctive risk factor for paradoxical embolism in patients with PFO.


Perceived variability reflects the reliability of individual items.
When confronted with many visual items, people can compute their variability accurately and rapidly, which facilitates efficient information processing and optimal decision making. However, how the visual system computes variability is still unclear. To investigate this, we implemented situations whereby estimates of variability based on several possible variability measures (e.g., range, standard deviation, and weighted standard deviation) could be differentiated, and then examined which best accounted for human variability perception. In three psychophysical experiments, participants watched two arrays of items with various orientations and judged which had more variable orientations. Results showed that perceived variability was most consistent with the weighted standard deviation based on the reliability of individual items. Specifically, participants gave less consideration to deviant orientations that were likely to be outliers, and greater consideration to salient orientations that were likely to be encoded precisely. This reliability-based weighted standard deviation suggests an efficient and flexible way of representing visual variability.