Improving care for families where children and parents have concurrent mental health problems.
When mental illness affects children and parents within the same family there is a need for close professional collaboration between the respective psychiatric teams. However, there is no nationally established precedence for this, and the area has not been investigated within the published literature. Retrospective case note study of 322 child psychiatric patients to estimate the prevalence of parental mental illness and analyse the degree of professional liaison taking place. Twenty-eight children had parents with concurrent mental health problems. Only four of these cases (14.2%) contained evidence of ongoing professional liaison between child and adult mental health teams. Inadequate liaison between child and adult services is a problem within the UK mental health system and detrimental to patient care. Recent national interest in establishing a more integrated family-focused service is encouraging, but will take time to implement and will not replace the need for separate specialist services. Efficient clinical collaboration must be developed at local levels to create a more comprehensive management strategy for children and parents with concurrent mental health problems.


A real-world study in advanced non-small cell lung cancer with de novo brain metastasis.
Brain metastases are the major cause of life-expectancy shortened for patients with lung cancer. The prognostic value of EGFR mutation subtypes and survival benefit of EGFR-tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC) patients with de novo brain metastasis is still not clear. Here, we present a real-world study nation-wide focusing on the prognostic value of genomic and therapeutic factors in overall survival (OS) of those patients. We enrolled a total of 233 patients diagnosed with advanced NSCLC and de novo BM from multi-medical centers across China. The enrolled patients were divided into 4 groups, including EGFR 19del, EGFR L858R, EGFR wild-type, and EGFR unknown groups. The median OS of patients with EGFR mutations and all patients were 29.0 and 25.0 months, respectively. There was significant difference in OS of patients among EGFR 19del (n=76), EGFR L858R (n=94), EGFR wild-type (n=46) and EGFR unknown (n=17) groups (30.5 vs 27.5 vs 16.0 vs 25.0, P=0.025). Patients treated by icotinib showed better OS than gefitinib and erlotinib (31.0 vs 25.5 vs 26.5, P=0.02). There was a difference in OS of patients received the whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or WBRT+SRS (20.0 vs 31.0 vs 30.0 months, P<0.001), respectively. In multivariate analysis, patients treated with icotinib had superior iPFS benefit than gefitinib and erlotinib (HR=0.86[95%CI (0.74-1.0)], P=0.04). Besides, the histology of non-adenocarcinomas, the number of BM (>3), and extracranial metastases status could have an independent negative impact on the OS of all patients (P<0.001). EGFR mutant NSCLC patients with de novo BM had a better OS than patients with EGFR wild type. Patients treated with icotinib had longer iPFS than gefitinib and erlotinib but not in OS. Non-adenocarcinomas, number of BM (>3) and extracranial metastases were independent negative prognostic factors in iPFS and OS of all patients. Prospective clinical trials are warranted to explore more effective multimodality in this population.


Voltammetry of ion transfer across a polarized room-temperature ionic liquid membrane facilitated by valinomycin: theoretical aspects and application.
Cyclic voltammetry is used to investigate the transfer of alkali-metal cations, protons, and ammonium ions facilitated by the complex formation with valinomycin at the interface between an aqueous electrolyte solution and a room-temperature ionic liquid (RTIL) membrane. The membrane is made of a thin (approximately 112 microm) microporous filter impregnated with an RTIL that is composed of tridodecylmethylammonium cations and tetrakis[3,5-bis(trifluoromethyl)phenyl]borate anions. An extension of the existing theory of voltammetry of ion transfer across polarized liquid membranes makes it possible to evaluate the standard ion-transfer potentials for the hydrophilic cations studied, as well as the stability constants (K(i)) of their 1:1 complexes with valinomycin, as log K(i) = 9.0 (H(+)), 11.1 (Li(+)), 12.8 (Na(+)), 17.2 (K(+)), 15.7 (Rb(+)), 15.1 (Cs(+)), and 14.7 (NH(4)(+)). These data point to the remarkably enhanced stability of the valinomycin complexes within RTIL, and to the enhanced selectivity of valinomycin for K(+) over all other univalent ions studied, compared to the conventional K(+) ion-selective liquid-membrane electrodes. Selective complex formation allows one to resolve voltammetric responses of K(+) and Na(+) in the presence of an excess of Mg(2+) or Ca(2+), which is demonstrated by determination of K(+) and Na(+) in the table and tap water samples.


Identification and characterization of a putative baculoviral transcriptional factor IE-1 from Choristoneura fumiferana granulovirus.
A gene that encodes a protein homologue to baculoviral IE-1 was identified and sequenced in the genome of the Choristoneura fumiferana granulovirus (ChfuGV). The gene has an 1278 nucleotide (nt) open-reading frame (ORF) that encodes 426 amino acids with an estimated molecular weight of 50.33 kDa. At the nucleotide level, several cis-acting regulatory elements were detected within the promoter region of the ie-1 gene of ChfuGV along with other studied granuloviruses (GVs). Two putative CCAAT elements were detected within the noncoding leader region of this gene; one was located on the opposite strand at -92 and the other at -420 nt from the putative start triplet. Two baculoviral late promoter motifs (TAAG) were also detected within the promoter region of the ie-1 gene of ChfuGV. A single polyadenylation signal, AATAAA, was located 18nt downstream of the putative translational stop codon of ie-1 from ChfuGV. At the protein level, the amino acid sequence data that was derived from the nucleotide sequence in ChfuGV IE-1 was compared to those of the Cydia pomonella granulovirus (CpGV), Xestia c-nigrum granulovirus (XcGV) and Plutella xylostella granulovirus (PxGV). The C-terminal regions of the granuloviral IE-1 sequences appeared to be more conserved when compared to the N-terminal regions. A domain, similar to the basic helix-loop-helix like (bHLH-like) domain in NPVs, was detected at the C-terminal region of IE-1 from ChfuGV (residues 387 to 414). A phylogenetic tree for baculoviral IE-1 was constructed using a maximum parsimony analysis. A phylogenetic estimation demonstrates that ChfuGV IE-1 is most closely related to that of CpGV.


Gait speed and hospitalization among ambulatory hemodialysis patients: USRDS special study data.
To assess the association of measured gait speed with hemodialysis (HD) patients' hospitalization, in conjunction with, and apart from, recent fall history. Gait speed was measured by a standard protocol and falls during the past 12 mo were ascertained for a prevalent multi-center HD cohort (n = 668) aged 20-92. Hospitalization during the past 12 mo was identified in the patient's clinic records, and the first hospitalization after gait speed assessment (or the competing event of death) was identified in the 2013 United States Renal Data System Standard Analysis Files. Slow gait speed, defined as < 0.8 m/s, characterized 34.7% of the patients, and 27.1% had experienced a recent fall. Patients with slow gait speed but without a history of recent falls were 1.79 times more likely to have been hospitalized during the past 12 mo (OR = 1.79, 95%CI: 1.11-2.88, P = 0.02), and patients with slow gait speed and a history of recent falls were over two times more likely to have been hospitalized (OR = 2.10, 95%CI: 1.19-3.73, P = 0.01), compared with patients having faster gait speed and no recent fall history. Prospective examination of gait speed/fall history status in relation to first hospitalization (or death) incurred by the end of follow-up December 31, 2011 also showed that slow gait speed was associated with these events in conjunction with a history of falls (HR = 1.54, 95%CI: 1.04-2.30, P = 0.03). The International Task Force on Nutrition and Aging reported that gait speed is a powerful predictor for older adults of adverse outcomes such as hospitalization. In our data, gait speed--apart from, as well as in conjunction with, recent fall history--was associated with HD patients' hospitalization for multiple causes. Gait speed may be a sensitive health indicator among HD patients across the age spectrum.


Innovative data tools: a suite for managing peer outreach to key affected populations in Viet Nam.
The paper tools used to monitor outreach work in all major cities in Viet Nam had substantial writing requirements for each contact with difficulty maintaining confidentiality. This paper describes the development of a Unique Identifier Code (UIC), a field data collection notebook (databook) and a computer data entry system in Viet Nam. The databook can document 40 individual clients and has space for commodity distribution, group contacts and needles/syringe collection for each month. Field implementation trials of the UIC and databook have been undertaken by more than 160 peer outreach workers to document their work with people who inject drugs (PWID) and sex workers (SW). Following an expanded trial in Hai Phong province, there have been requests for national circulation of the databook to be used by peer educators documenting outreach to PWID, SW and men who have sex with men. The standardized UIC and databook, in a variety of locally adapted formats, have now been introduced in more than 40 of the 63 provinces in Viet Nam. This development in Viet Nam is, to our knowledge, the first example of the combination of a confidential UIC and an innovative, simple pocket-sized paper instrument with associated customized data-entry software for documenting outreach.


Multigenerational caregiving and well-being: distress of middle-aged daughters providing assistance to elderly parents.
This article investigates whether being a caregiver of an elderly parent and the caregiver's involvement in multiple roles increases distress in middle-aged women. Previous studies assumed that providing care to frail parents causes distress in women, in particular when they have other social roles as well. Longitudinal data were collected within a cohort of middle-aged women (n = 934; n = 743). The acquisition or loss of the caregiver role did not appear to affect levels of distress of middle-aged women, nor did additional roles of caregivers increase distress levels or caregiver role strain. Most distressed were women not performing any major social role, suggesting that the lack of social roles rather than the multiplicity of roles is associated with distress. The caregiver role might even reduce distress when women have very few other roles. Findings are explained in terms of the role scarcity, the role expansion and role accumulation hypotheses of role theory.


Effect of arteether on electrocardiogram in the patients of falciparum malaria--a preliminary study.
The effect of intramuscular arteether (150 mg daily for 3 days) on electrocardiogram was studied in 16 patients having falciparum malaria. This included three patients with cerebral malaria, three patients with jaundice (S. bilirubin > 3 mg per cent) and ten patients with uncomplicated malaria. Five patients had tachycardia prior to arteether treatment. The mean RR interval before starting the treatment was 0.59 sec which increased progressively--0.60, 0.68 and 0.69 sec on Day 1, 2 and 3 respectively after starting the treatment. There was no significant difference statistically in the mean corrected QT interval (p > 0.05), PR interval (p > 0.05), QRS duration (p > 0.05) and diastolic BP (p > 0.05) before starting and at the end of treatment on Day 3. One patient had developed first degree heart block (PR 0.24), while another patient had prolonged QTc (0.48 sec) on Day 3. Subsequent ECG of both these patients was normal on Day 5. The profile of ECG changes was same in the patients of uncomplicated and complicated malaria. Absence of any significant effect on BP and ECG changes precludes the significant effect of arteether on the cardiovascular system when compared to quinine which may cause hypotension, arrhythmia and QTc prolongation.


Effect of Aging on the Mechanical Properties of Highly Transparent Fluoropolymers for the Conservation of Archaeological Sites.
In recent years, fluoropolymers have found numerous applications in the architectural field because of their combination of mechanical-chemical resistance and high transparency. In the present work, commercial fluorinated polymers, such as perfluoro alkoxy (PFA) and ethylene tetrafluoroethylene copolymer (ETFE), have been evaluated for use as protective and transparent layers on monumental and archaeological sites (to preserve mosaics or frescoes) during the phases of restoration or maintenance outdoors. Considering this specific application, the present study was developed by evaluating the evolution of the mechanical (tensile, tear propagation resistance, and low-velocity impact tests) and chemical (FTIR and DSC analysis) properties of the films after accelerated UV aging. The results that were obtained demonstrated the high resistance capacity of the ETFE, which exhibits considerably higher elastic modulus and critical tear energy values than PFA films (1075.38 MPa and 131.70 N/mm for ETFE; 625.48 MPa and 59.06 N/mm for PFA). After aging, the samples exhibited only a slight reduction of about 5% in the elastic modulus for both polymers and 10% in the critical tear energy values for PFA. Furthermore, the differences in impact resistance after aging were limited for both polymers; however, the ETFE film showed higher peak force than the PFA films (82.95 N and 42.22 N, respectively). The results obtained demonstrated the high resistance capacity of ETFE films, making them the most suitable candidate for the considered application.


Free deep circumflex iliac artery vascularised bone flap for reconstruction of the distal radius: planning with CT angiography.
Distal radius fractures in the younger population are often comminuted and intra-articular, which can increase the complexity of their management. In addition, these patients tend to place high demands on their wrists, and the prevention of functional arthritis necessitates excellent anatomical reduction. Complicated cases such as these are often limited in their management options. We present a complex case of distal radius fracture and bone loss in which initial therapy with nonvascularized bone graft failed, and osteomyelitis was a further complicating factor. With the aid of preoperative planning with computed tomographic angiography (CTA), a deep circumflex iliac artery (DCIA) bone flap was able to be assessed as a reconstructive option. The use of preoperative CTA, the first description of such imaging in this role, was able to delineate the bone to be harvested, confirm its vascular supply, and plan flap harvest. The use of a vascularized bone flap in this setting was thus undertaken and was able to provide an autologous anatomical support for the wrist while reducing the risk of recurrent infection and still preserving internal fixation. This unique application of the free DCIA bone flap was potentiated by CTA, achieving complete healing and good functional outcomes.


Deep-Kcr: accurate detection of lysine crotonylation sites using deep learning method.
As a newly discovered protein posttranslational modification, histone lysine crotonylation (Kcr) involved in cellular regulation and human diseases. Various proteomics technologies have been developed to detect Kcr sites. However, experimental approaches for identifying Kcr sites are often time-consuming and labor-intensive, which is difficult to widely popularize in large-scale species. Computational approaches are cost-effective and can be used in a high-throughput manner to generate relatively precise identification. In this study, we develop a deep learning-based method termed as Deep-Kcr for Kcr sites prediction by combining sequence-based features, physicochemical property-based features and numerical space-derived information with information gain feature selection. We investigate the performances of convolutional neural network (CNN) and five commonly used classifiers (long short-term memory network, random forest, LogitBoost, naive Bayes and logistic regression) using 10-fold cross-validation and independent set test. Results show that CNN could always display the best performance with high computational efficiency on large dataset. We also compare the Deep-Kcr with other existing tools to demonstrate the excellent predictive power and robustness of our method. Based on the proposed model, a webserver called Deep-Kcr was established and is freely accessible at http://lin-group.cn/server/Deep-Kcr.


Quality of life after treatment for laryngeal carcinomas.
The objective of this study was to evaluate the impact of different surgical treatments as well as of radiotherapy for laryngeal carcinomas on health-related quality of life (QL). In a prospective, randomized multicenter study (five university hospitals in Germany), a total of 146 patients with laryngeal carcinomas (UICC stages: I-IV) underwent different surgical treatments (32 total laryngectomies, 81 CO(2) laser microsurgical partial laryngectomies, 33 open partial laryngectomies). Postoperative radiotherapy was performed in 44 patients. QL data were obtained by using the EORTC QLQ-C30 questionnaire (developed by the European Organization for Research and Treatment of Cancer). Impaired QL data were seen after total laryngectomy and after radiotherapy. Radiotherapy seemed to have more impact on QL than surgical treatment. Global QL was not affected by any treatment. In general, the QL data were not as discriminating as presumed. To evaluate coping abilities, objective measures (voice, swallowing, breathing) should be obtained for comparison in further investigations.


Unraveling the Mechanisms of Behaviors Associated With AUDs Using Flies and Worms.
Alcohol use disorders (AUDs) are very common worldwide and negatively affect both individuals and societies. To understand how normal behavior turns into uncontrollable use of alcohol, several approaches have been utilized in the last decades. However, we still do not completely understand how AUDs evolve or how they are maintained in the brains of affected individuals. In addition, efficient and effective treatment is still in need of development. This review focuses on alternative approaches developed over the last 20 years using Drosophila melanogaster (Drosophila) and Caenorhabditis elegans (C. elegans) as genetic model systems to determine the mechanisms underlying the action of ethanol (EtOH) and behaviors associated with AUDs. All the results and insights of studies over the last 20 years cannot be comprehensively summarized. Thus, a few prominent examples are provided highlighting the principles of the genes and mechanisms that have been uncovered and are involved in the action of EtOH at the cellular level. In addition, examples are provided of the genes and mechanisms that regulate behaviors relevant to acquiring and maintaining excessive alcohol intake, such as decision making, reward and withdrawal, and/or relapse regulation. How the insight gained from the results of Drosophila and C. elegans models can be translated to higher organisms, such as rodents and/or humans, is discussed, as well as whether these insights have any relevance or impact on our understanding of the mechanisms underlying AUDs in humans. Finally, future directions are presented that might facilitate the identification of drugs to treat AUDs.


[Micro-ribonucleic acids participate in electroacupuncture intervention-induced improvement of ischemic stroke].
Ischemic stroke is a major cause of permanent disability and death in adults, and electroacupuncture (EA) intervention has a positive role in improving neurological function in patients with ischemic stroke through a series of complex processes. In the present paper, we make a review about the development of researches on the involvement of micro-ribonucleic acid (miRNA) in ischemic stroke from excitatory amino acid toxicity, oxidative stress, inflammatory response, apoptosis and necrosis, and particularly sum up outcomes of researches about the roles of miRNAs in EA-induced improvement of neurological function in experimental cerebral ischemia animals. EA treatment can 1) balance levels of miRNAs (such as mir-126 and mir-328, etc.) to promote angiogenesis of ischemic cerebral cortex tissue by regulating expression of vascular endothelial growth factor family genes and proteins; 2) promote nerve regeneration by up-regulating serum miR-124 and hippocampal miR-132 expression to possibly facilitate cerebral repair and reduce cognitive dysfunction respectively via related proteins; 3) reduce cerebral edema via modulating expression of some miRNAs to control expression of aquaporin, matrix metalloproteinases, etc. and 4) suppress inflammatory response via up-regulating expression of miRNAs to inhibit expression of NF-κB, TNF-α, etc. in the local cerebral tissue. As a result, the neurological function is bettered after EA intervention.


The Effect of Molar Mass and Charge Density on the Formation of Complexes between Oppositely Charged Polyelectrolytes.
The interactions between model polyanions and polycations have been studied using frontal continuous capillary electrophoresis (FACCE) which allows the determination of binding stoichiometry and binding constant of the formed polyelectrolyte complex (PEC). In this work, the effect of the poly(l-lysine) (PLL) molar mass on the interaction with statistical copolymers of acrylamide and 2-acrylamido-2-methyl-1-propanesulfonate (PAMAMPS) has been systematically investigated for different PAMAMPS chemical charge densities (15% and 100%) and different ionic strengths. The study of the ionic strength dependence of the binding constant allowed the determination of the total number of released counter-ions during the formation of the PEC, which can be compared to the total number of counter-ions initially condensed on the individual polyelectrolyte partners before the association. Interestingly, this fraction of released counter-ions, which was strongly dependent on the PLL molar mass, was almost independent of the PAMAMPS charge density. These findings are useful to predict the binding constant according to the molar mass and charge density of the polyelectrolyte partners.


Is it safe to back out pedicle screws after augmentation with polymethyl methacrylate or calcium phosphate cement? A biomechanical study.
Biomechanical cadaveric study. To determine the torque required to remove pedicle screws augmented with polymethyl methacrylate (PMMA) or calcium phosphate cement (CPC); thus, proving the safety of back out of augmented screws in the osteopotoric model, which would be a more dangerous setting than the nonosteoporotic model. To our knowledge, no earlier study has characterized the safety of backing out pedicle screw augmented with PMMA or CPC. Pedicle screws were inserted in 24 osteoporotic vertebrae (48 pedicles). The maximal insertion torque and pullout strength of each screw were recorded. After pullout of the pedicle screws, the vertebrae were then randomized into 2 groups of 12 (24 pedicles) each. PMMA was injected into the pedicles in the first group and CPC was injected into the second group after which the pedicle screws were inserted. The pedicle screws were inserted into the pedicle holes augmented with PMMA or CPC, respectively. Finally, all augmented screws were backed out and the maximal removal torque was recorded using a digital torque wrench. Throughout the study, no incidence of pedicle or lamina fractures was observed. The average insertion torque was 0.5±0.27 and 0.45±0.29 N·m for groups 1 and 2, respectively (P=0.724). The average pullout strength was 723.1±391.7 and 671.2±383.0 N (P=0.950). After cement augmentation, the average removal torque was 0.77±0.31 and 0.81±0.26 N·m for PMMA and CPC, respectively (P=0.494). The results of this study showed that pedicle screws can be easily and safely backed out after augmentation with PMMA or CPC. The result of CPC, however, may only be valid before any bony ingrowth.


Tumors and Tumorlike Conditions of Which Every Orthopaedic Surgeon Should Be Aware.
All orthopaedic surgeons during the course of their career will likely encounter both benign and malignant musculoskeletal neoplasms. Given the rarity of these entities and the stress conferred by diagnosing a tumor or tumorlike condition, many orthopaedic surgeons may benefit from a review of the contemporary treatment of such patients. Whether in the outpatient clinic or following a high-energy trauma, special attention should be given to concerning signs and symptoms that will aid in the workup of children and adults with a possible tumor. A thorough and logical workup in this manner will often lead to a definitive diagnosis such as metastatic bone disease or perhaps a benign lesion. In these instances, the informed general orthopaedic surgeon or subspecialist may choose to treat the patient independently. However, if the workup is inconclusive or if the diagnosis is even questionably malignant, referral to an orthopaedic oncologist should be sought as to avoid pitfalls in diagnosis and treatment.


Envenomations as a novel drug-seeking method.
Drug seekers have often sought narcotics and benzodiazepines through subjective reports of severe pain. We report 2 patients who claimed repeated envenomation to receive narcotic administration; 1 claimed black widow bite on 8 occasions at 7 separate healthcare facilities, the other claimed to have been bitten by a copperhead snake on 7 occasions at 4 separate healthcare facilities. A 3rd patient complained of lionfish envenomation with no tissue reaction and was refused analgesia. Inconsistent clinical presentations of envenomations may signal drug-seeking behaviors.


Chlorhexidine gel used as antiseptic in periodontal pockets.
The aim of this study was to evaluate the adjunctive benefit offers by the administration of a chlorhexidine based local drug deliver (Chlo-SITE) into periodontal socket after a full mouth disinfection session. The study design was a randomized, crossover, clinical trial conducted on 60 non-smokers subjects with chronic periodontitis. Each volunteer was subjected to a one-stage full mouth disinfection session and, immediately after that, test product (Chlo-SITE) was inserted in 1 pocket in 2 quadrant. The 1° and 4° quadrant were used for the study with the application of antiseptic (Test); the 2° and 3° as a control. Periodontal probe (PD), bleeding on probing (BOP) and plaque index (PI) was collected at baseline (T0), after 7 days (T1), after 4 weeks (T2). The results of this study suggest that the application of xanthan-based chlorhexidine gel (Xan-CHX) offers a great benefit in improving of the indices in chronic periodontitis.


Gender and tachycardia: independent modulation of platelet reactivity in patients with atrial fibrillation.
Female patients with atrial fibrillation (AF) experience increased risk of thromboembolism compared to males, an observation that is reflected by its inclusion in the CHA2DS2VASc score. New onset AF (often associated with tachycardia) also confers upon patients increased thromboembolic risk. The mechanisms underlying this risk are uncertain, but new onset AF is associated with profound impairment of platelet nitric oxide (NO) signalling. Given that cardiovascular responses to catecholamines are gender-dependent, and that the presence of tachycardia in new onset AF may represent a response to catecholaminergic stimulation, we explored the potential impact of gender and tachycardia on platelet aggregation and NO signalling. Interactions were sought in 87 AF patients between the extent of adenosine diphosphate (ADP)-induced platelet aggregation, the anti-aggregatory effects of the NO donor, sodium nitroprusside, gender, and admission heart rate. The potential impact of platelet expression of thioredoxin-interacting protein (Txnip) was also evaluated. Analysis of covariance confirmed the presence of physiological antagonism between platelet ADP and NO responses [F (1, 74) = 12.212, P < 0.01], while female sex correlated with impaired NO responses independent of platelet aggregability [F (2, 74) = 8.313, P < 0.01]. Admission heart rate correlated directly with platelet aggregation (r = 0.235, P < 0.05), and inversely with NO response (r = -0.331, P < 0.01). Txnip expression varied neither with gender nor with heart rate. These results indicate that gender and heart rate are independent determinants of platelet function. Prospective studies of the putative benefit of reversal of tachycardia on restoration of normal platelet function are therefore a priority.


Growth factor delivery through electrospun nanofibers in scaffolds for tissue engineering applications.
Tissue engineering scaffolds should ideally mimic the natural ECM in structure and function. Electrospun nanofibrous scaffolds are easily fabricated and possess a biomimetic nanostructure. Scaffolds can mimic ECM function by acting as a depot for sustained release of growth factors. bFGF, an important growth factor involved in tissue repair and mesenchymal stem cell proliferation and differentiation, is a suitable candidate for sustained delivery from scaffolds. In this study, we present two types of PLGA nanofibers incorporated with bFGF, fabricated using the facile technique of blending and electrospinning (Group I) and by the more complex technique of coaxial electrospinning (Group II). bFGF was randomly dispersed in Group I and distributed as a central core within Group II nanofibers; both scaffolds showed similar protein encapsulation efficiency and release over 1-2 weeks. Although both scaffold groups favored bone marrow stem cell attachment and subsequent proliferation, cells cultured on Group I scaffolds demonstrated increased collagen production and upregulated gene expression of specific ECM proteins, indicating fibroblastic differentiation. The study shows that the electrospinning technique could be used to prolong growth factor release from scaffolds and an appropriately sustained growth factor release profile in combination with a nanofibrous substrate could positively influence stem cell behavior and fate.


Epigenetic Modulation of Human Induced Pluripotent Stem Cell Differentiation to Oligodendrocytes.
Pluripotent stem cells provide an invaluable tool for generating human, disease-relevant cells. Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system, characterized by myelin damage. Oligodendrocytes are the myelinating cells of the central nervous system (CNS); they differentiate from progenitor cells, and their membranes ensheath axons, providing trophic support and allowing fast conduction velocity. The current understanding of oligodendrocyte biology was founded by rodent studies, where the establishment of repressive epigenetic marks on histone proteins, followed by activation of myelin genes, leads to lineage progression. To assess whether this epigenetic regulation is conserved across species, we differentiated human embryonic and induced pluripotent stem cells to oligodendrocytes and asked whether similar histone marks and relative enzymatic activities could be detected. The transcriptional levels of enzymes responsible for methylation and acetylation of histone marks were analyzed during oligodendrocyte differentiation, and the post-translational modifications on histones were detected using immunofluorescence. These studies showed that also in human cells, differentiation along the oligodendrocyte lineage is characterized by the acquisition of multiple repressive histone marks, including deacetylation of lysine residues on histone H3 and trimethylation of residues K9 and K27. These data suggest that the epigenetic modulation of oligodendrocyte identity is highly conserved across species.


Food and Drug Administration, HHS.--General; dental radiographs. Final recommendations.
The agency is issuing a recommendation that insurance carriers and other remote parties refrain from requiring administrative dental x-ray examinations. Administrative dental x-ray examinations are those required by a remote third party (other than a patient's dentist or physician) for reasons not related to the patient's immediate dental needs. These dental x-ray examinations may result in unnecessary radiation exposure to the patient. This recommendation is a part of the agency's effort to minimize unnecessary exposure of the public to ionizing radiation.


Reduced white matter integrity as a neural correlate of social cognition deficits in schizophrenia.
The pathology of schizophrenia is thought to involve multiple gray and white matter regions. A number of studies have revealed impaired social cognition in schizophrenia. Some evidence suggests an association of this social cognition deficit with gray matter reductions in 'social brain' areas. However, no study has yet revealed the association between social cognition abilities and white matter abnormalities in schizophrenia patients. Twenty-six schizophrenia patients and 27 healthy controls underwent the Perception of Affect Task (PAT), which consisted of four subtasks measuring different aspects of emotion attribution. Voxelwise group comparison of white matter fractional anisotropy (FA) was performed using tract-based spatial statistics (TBSS). The relation between impaired social cognition ability and FA reduction was examined in patients for each subtask, using simple regression analysis within brain areas that showed a significant FA reduction in patients compared with controls. The same correlational analysis was also performed for healthy controls in the whole brain. Schizophrenia patients showed reduced emotion attribution ability compared with controls in all four subtasks. The facial emotion perception subtask showed a significant correlation with FA reductions in the left occipital white matter region and left posterior callosal region. The correlational analyses in healthy controls revealed no significant correlation of FA with any of the PAT subtasks. Our voxelwise correlational analysis of white matter provided a potential neural basis for the social cognition impairments in schizophrenia, in support of the disconnection hypothesis.


Reduced stress-induced hyperthermia in mGluR5 knockout mice.
It hs been suggested that metabotropic glutamate receptor subtype 5 (mGluR5) play a role in the expression of anxiety, based on anxiolytic-like effects of the selective mGluR5 antagonist MPEP (2-methyl-6-(phenylethynyl)pyridine) in rodent models of anxiety, including stress-induced hyperthermia (SIH). To examine the suggested role of mGlu5 receptors in the expression of anxiety, we examined the stress response in mice lacking mGluR5 in several variations of the SIH procedure. In this paradigm, stress causes a mild increase in body temperature that can be blocked by known anxiolytic agents. Three procedures were employed: classical SIH using rectal-probe measurement of body temperature, and radiotelemetric measurement of body temperature in response to either saline injection or to the introduction of an intruder into the home cage. In all three procedures the mGluR5-knockout mice displayed a significant attenuation of the hyperthermic response to stress compared to littermate wild-type control mice. To confirm that our observations were likely to be due to the absence of mGluR5 in the knockout mice we also tested the effect of the recently described selective mGluR5 antagonist MTEP (3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine) in both the wild-type and mGluR5 knockout mice. Administration of MTEP in the wild-type mice, but not the mGluR5 knockout mice, attenuated SIH. That the mGluR5 knockout mice displayed an anxiolytic-like phenotype and that the mGluR5 antagonist, MTEP, showed a anxiolytic-like effect only in mice possessing mGluR5 further supports the suggestion that mGluR5 antagonists may be useful in the treatment of anxiety.


Laws restricting health insurers' use of genetic information: impact on genetic discrimination.
Since 1991, 28 states have enacted laws that prohibit insurers' use of genetic information in pricing, issuing, or structuring health insurance. This article evaluates whether these laws reduce the extent of genetic discrimination by health insurers. From the data collected at multiple sites, we find that there are almost no well-documented cases of health insurers either asking for or using presymptomatic genetic test results in their underwriting decisions, either (a) before or after these laws have been enacted or (b) in states with or without these laws. By using both in-person interviews with insurers and a direct market test, we found that a person with a serious genetic condition who is presymptomatic faces little or no difficulty in obtaining health insurance. Furthermore, there are few indications that the degree of difficulty varies according to whether a state regulates the use of genetic information. Nevertheless, these laws have made it less likely that insurers will use genetic information in the future. Although insurers and agents are only vaguely aware of these laws, the laws have shaped industry norms and attitudes about the legitimacy of using this information.


[Analysis of community intervention effects for diabetic eye diseases in Shanghai Xinjing community from 2016 to 2018].
Objective: To analyze the effects of community-based interventions for diabetic eye diseases in Xinjing community, Shanghai from 2016 to 2018. Methods: Based on the project of "Establishment of Service Model for Comprehensive Prevention and Treatment of Diabetic Eye Diseases in Shanghai", the participants were not suffering diabetic retinopathy (DR) in Xinjing community in 2016 before interventions and received community-based interventions for diabetic eye diseases. The incidence of DR, visual acuity and awareness of DR were used as evaluation indicators to analyze the effects of interventions for diabetic eye diseases in the community. Results: A total of 537 patients were included in this study, the incidence of DR among diabetic patients in Xinjing community was 7.6% after interventions. The duration of diabetes (OR= 1.065) and HbA1c (OR= 1.090) were the risk factors of DR. Before and after the interventions, the patients with monocular low vision and binocular low vision were 27 cases (5.0%), 8 cases (1.5%), 19 cases (3.5%) and 7 cases (1.3%) respectively. After interventions, the awareness on the prevention and treatment of DR increased significantly, and the proportion of regular visits to ophthalmology examination, diet control and physical exercise also increased significantly. Conclusion: Community-based interventions for diabetic eye diseases are helpful to improve the awareness of DR prevention and control, reduce the incidence of DR.


Effect of high pressure processing on the gel properties of salt-soluble meat protein containing CaCl2 and κ-carrageenan.
The effects of high pressure processing (HPP) on the water-binding capacity and texture profile (TPA) of salt-soluble meat protein (SSMP) containing 0.2% CaCl2 and 0.6% κ-carrageenan (SSMP-CK) gels were investigated. The results showed that 300-400 MPa improved water-binding capacity and decreased TPA parameters of SSMP-CK gels (P<0.05), while 100 MPa could increase hardness and chewiness of the gels. The thermal transition temperature peak for the myosin head (Tpeak1) of SSMP disappeared on addition of CaCl2 and κ-carrageenan. 300 MPa produced a new peak, and caused a shift of the NH-stretching left peak and amide I and the disappearance of NH-stretching right peak. The destruction of network structure and the weakening of molecular interaction within the pressurized gels could result in the decrease of TPA parameters. Thus gelling properties could be modified by HPP, κ-carrageenan and Ca(2+). It is of interest to develop low-fat and sodium-reduced meat products.


Study on the prevalence and neonatal lethality in patients with selected congenital anomalies as per the data of the National Registry of Congenital Anomalies of Argentina.
Congenital anomalies (CAs) account for 26% of infant mortality in Argentina. The lethality rate for CAs measures the risk of death among affected infants. To describe the prevalence at birth of a group of selected CAs, to estimate the neonatal lethality rate, and to examine its association with different variables. The study was conducted using data provided by the National Registry of Congenital Anomalies. Prevalences of encephalocele, spina bifida, gastroschisis, omphalocele, diaphragmatic hernia, esophageal atresia, intestinal atresia, or anorectal malformation were estimated (2009-2013 period). Lethality was assessed at 7 and 28 days of life in affected infants with an isolated anomaly (2013). Association with the following variables was analyzed: sex, gestational age, birth weight, antenatal ultrasound screening, percentage of unmet basic needs in the district where the mother lives, geographic region, and level of care at the hospital where the delivery took place. Gastroschisis was the most prevalent CA (8.53/10,000 births), while diaphragmatic hernia was the CA with the highest neonatal lethality rate (66.67%). Out of all selected CAs, there was a significant association between an higher gestational age and survival at 7 days -OR: 0.81 (0.70-0.95)- and survival at 28 days -OR: 0.79 (95% confidence interval |-CI-|: 0.68-0.91)-. A higher percentage of unmet basic needs was associated with a higher lethality for diaphragmatic hernia -OR: 1.59 (95% CI: 1.30-1.95)- and for intestinal atresia or anorectal malformation -OR: 16.00 (95% CI: 1.63-157.24)-. The high prevalence of gastroschisis is consistent with the increase observed globally. Prematurity and a high percentage of unmet basic needs increased the risk of death among affected infants.


High-Quality Genome Resource of Clonostachys rosea Strain CanS41 by Oxford Nanopore Long-Read Sequencing.
Clonostachys rosea is a necrotrophic mycoparasitic fungus with excellent biological control ability against numerous fungal plant pathogens. Here, we performed genomic sequencing of C. rosea strain CanS41 using Oxford Nanopore sequencing technology. We generated a high-quality genome assembly (>99.99% accuracy), which comprised 26 contigs containing 60.68 Mb sequences with a GC content of 48.55% and a repeat content of 8.38%. The N50 contig length is 3.02 Mb. In total, 20,818 protein-coding genes were identified and functionally annotated. Genes encoding secreted proteins and carbohydrate-active enzymes as well as secondary metabolic gene clusters were also identified and analyzed. In summary, the high-quality genome assembly and gene annotation provided here will allow further exploration of biological functions and enhance biological control ability of C. rosea.


Malignant ascites: demographics, therapeutic efficacy and predictors of survival.
Demographics, treatment patterns, treatment efficacy and clinical predictors of survival were studied in 76 consecutive patients with malignant ascites. Sixty-four percent of patients were female, and mean age was 63 years. The most common primary malignancies were ovarian cancer, carcinoma of unknown primary, breast cancer, colorectal carcinoma and lymphoma. Ascites was present at the time of diagnosis of malignancy in 39%. Diuretics were administered in 22% of patients with a 22% response in ascites; all responding patients had hepatic metastases. Systemic anticancer therapy was administered in 38%, with a 38% objective response in ascites. Five peritoneovenous shunts were placed, with one shunt functional at 2 weeks. Paracentesis was performed in 71% of patients with complications potentially due to paracentesis occurring in 24% of these patients. Median survival was 78 days from the clinical diagnosis of ascites. Multivariate analysis revealed significantly shortened survival in patients with liver metastases and elevated serum bilirubin, while ovarian cancer was a significant independent predictor of prolonged survival.


A New Animal Model for Pathological Subcutaneous Fibrosis: Surgical Technique and in vitro Analysis.
Fibrosis is a condition that affects the connective tissue in an organ or tissue in the restorative or responsive phase as a result of injury. The consequences of excessive fibrotic tissue growth may lead to various physiological complications of deformity and impairment due to hypertrophic scars, keloids, and tendon adhesion without understating the psychological impact on the patient. However, no method accurately quantifies the rate and pattern of subcutaneous induced hypertrophic fibrosis. We, therefore, devised a rodent excisional model to evaluate the extent of fibrosis with talc. Tissue specimens were set on formalin, and paraffin sections for histological, immunohistochemical, and molecular analysis talc was used to induce the fibroproliferative mechanism typical of hypertrophic scars. This pathway is relevant to the activation of inflammatory and fibrotic agents to stimulate human hypertrophic scarring. This model reproduces morpho-functional features of human hypertrophic scars to investigate scar formation and assess potential anti-scarring therapies.


Glycine supplementation to breast-fed piglets attenuates post-weaning jejunal epithelial apoptosis: a functional role of CHOP signaling.
This study was conducted to test the hypothesis that preweaning glycine supplementation to breast-fed piglets alleviated the post-weaning apoptosis of jejunal epithelium through CHOP signaling. Seven-day-old sow-reared piglets were orally administrated with 0, 50, 100, or 200% of glycine intake from sow's milk twice daily for 14 days and then were weaned at 21 days of age. Tissue samples were collected at 28 days of age for determining intestinal morphology, serum diamine oxidase (DAO) activity, abundances of proteins involved in ER stress and apoptosis. Glycine (100-200%) administration increased villus height, the ratio of villus height to crypt depth in the jejunum. Glycine supplementation (200%) enhanced average daily weight gain during the first 2 weeks post-weaning. Serum DAO activity and jejunal epithelium apoptosis were decreased, but the number of goblet cells in the jejunum was increased. Western blot analysis showed that 100-200% glycine enhanced the protein levels of occludin, claudin-1, and zonula occludens (ZO)-1 without affecting those of claudin-3, ZO-2, and ZO-3. Further studies showed that protein abundances of glucose-regulated protein 78 (BiP/GRP78) and p-IRE1α, instead of ATF6α, were reduced by glycine. Among the proteins related to apoptosis, abundances of CHOP and p53 were reduced, whereas those of Bcl-2 and Bcl-xL were enhanced in the jejunum of 100-200% glycine-supplemented piglets. Collectively, our results indicated that preweaning glycine supplementation improved the intestinal development of post-weaning piglets. The beneficial effect of glycine was associated with improved intestinal mucosal barrier and reduced apoptosis of enterocytes through CHOP signaling.


[Inhibitory effect of valproic acid on xenografted Kasumi-1 tumor growth in nude mouse and its mechanism].
To investigate in vivo inhibitory effect of histone deacetylase (HDAC) inhibitor valproic acid (VPA) on xenografted Kasumi-1 tumor in nude mice and its mechanism. Xenografted Kasumi-1 tumor mouse model was established by subcutaneous inoculation of Kasumi-1 cells. Xenotransplanted nude mice were assigned into control or VPA treatment groups. Volume of the xenografted tumors was measured and compared between the two groups. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) was applied to detection of tumor cell apoptosis. The gene expression of GM-CSF, HDAC1, Ac-H3 and survivin was studied with semi-quantitative RT-PCR and Western blotting. ChIP method was used to assay the effects of VPA on acetylation of histone H3 within GM-CSF promoter region. (1) VAP significantly inhibited xenografted Kasumi-1 tumor growth. The calculated inhibition rate was 57.25%. (2) Morphologic study showed that VPA induced differentiation and apoptosis of Kasumi-1 tumor cells. The apoptosis index of VAP treatment group [(3.661 +/- 0.768)%] was significantly higher than that of control group [(0.267 +/- 0.110)%]. (3) Comparing to those in control group, the level of nuclear HDAC1 protein was significantly decreased, the Ac-H3 protein expression level was increased, the mRNA and protein expression levels of GM-CSF and acetylation of histone H3 were remarkably increased, and the gene expression level of survivin significantly decreased in VPA treatment group. VAP significantly inhibits xenografted Kasumi-1 tumor growth and induces tumor cell differentiation and apoptosis. The mechanism may be decrease of survivin gene expression, inhibition of nuclear expression of HDAC, promotion of histone protein acetylation level and acetylation of histone H3 within GM-CSF promoter region, and increase of GM-CSF transcription.


And they all lived unhappily ever after: Positive and negative emotions in American and Russian picture books.
The U.S. and Russian cultural contexts are thought to foster different models of emotion, with the former emphasizing positive emotions more and negative emotions less than the latter. Little is known about the ways in which parents transmit these models of emotions to children. Cultural products, such as popular storybooks, may serve to provide important tools of transmission. Two studies examined similarities and differences in the extent to which children's books from these cultural contexts depict emotions. In Study 1, U.S., Russian American, and Russian parents described the extent to which books that they recently read to their children depict positive and negative emotions. Although no differences emerged for depictions of positive emotions, U.S. parents described reading books with lower levels of negative emotions than Russian parents, with Russian American parents in between. These differences were partially due to parental beliefs about sadness. In Study 2, verbal and nonverbal depictions of emotions were compared for sets of popular children's books from the U.S. and Russia. U.S. books verbally referenced anger and sadness and depicted happiness, anger, and fear faces less frequently than Russian books. Taken together, these studies suggest that American and Russian parents value and expose their children to different depictions of emotions, particularly negative emotions. Future studies need to examine the ways in which children in these cultural contexts interpret depictions of emotions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


[The thermodilution determination of right ventricular volumes and ejection fraction in the critical patient. Volumetric vs pressure measurement assessment].
The widespread use of hemodynamic investigation techniques, allowed a better understanding of the right ventricle (RV) pathophysiology and led to progressive reevaluation of its role. A modification of the classical Swan-Ganz catheter, made possible the measurement of the ejection fraction (EF) and of the end-systolic and end-diastolic volumes of RV just by the simple application of the thermodilution technique. In this paper, we first refreshed the basic theoretical principles of the technique and then presented our preliminary results of one-year experience in ICU. A non-homogeneous group of 36 critically ill patients (septic shock 17, COPD 13 and ARDS 6) was studied. Specifically we found that neither the data of central venous pressure nor those of RV end diastolic pressure, were able to estimate the real preload, i.e. RV end diastolic volume (r = 0.01 and r = 0.03 respectively with "p" not significant). We compared the data of RV EF with that of the end systolic pressure/volume (P/V) ratio in a group of patients before and during the administration of dobutamine to evaluate their sensitivity to identify changes of contractility. The results obtained support the superiority of RV end systolic P/V ratio over RV EF to detect variations of contractile status. We conclude that the use of the thermodilution technique to measure the volumes of RV, allows a real evaluation of the preload. At the same time it avoids all the problems associated with the measurement of transmural pressure and with the changes produced by shifting of intrapleural pressure. Finally the end systolic volume may be combined with the pressure data to estimate the contractile status and, in our experience, this parameter has proved more sensitive than EF in order to detect changes of contractility of the right ventricle.


Improving the quality of drug error reporting.
Drug errors are a common and persistent problem in health care and are also associated with serious adverse events. Reporting has become the cornerstone of learning from errors, but is not without its imperfections. The aim of this study is to improve reporting and learning from drug errors through investigating the contributory factors in drug errors and quality of reporting in an acute hospital. A retrospective, random sample of 991 drug error reports from 1999 to 2003 were subjected to quantitative and qualitative analysis. This was followed by 40 qualitative interviews with a volunteer, multi-disciplinary sample of health professionals. The combined analysis has been used to develop a knowledge base for improved drug error reporting. The quality of reports varied considerably, and 27% of reports lacked any contributory factors. Documentary analysis revealed a focus on individuals, sometimes culminating in blame without obvious justification. Doctors submitted few reports, and there were notable differences in reporting according to clinical location. Communication difficulties commonly featured in causation, and high workload and interruptions were predominant contributory factors in the interview data. Interviewees viewed causation as multifactorial, including cognitive and psychosocial factors. Organizational orientation to error was predominantly perceived by interviewees as individual rather than systems-based. Staff felt obliged to report but rarely received feedback. IMPLICATIONS AND CONCLUSION: Drug errors are multifactorial in causation. Current reporting schemes lack a theoretical basis, and are unlikely to capture the information required to ensure learning about causation. Health professionals have reporting fatigue and some remain concerned that reporting promotes individual blame rather than an examination of systems factors. Reporting can be strengthened by human error theory, redesigned to capture a range of contributory factors, facilitate learning and foster supportive actions. It can also be feasible in routine practice. Such an approach should be examined through multi-centred evaluation.


Use of systemic fipronil and imidacloprid to control regeneration pests of loblolly pine.
Regeneration pests of loblolly pine (Pinus taeda L.) threaten growth and survival in intensively managed loblolly pine plantations throughout the southeastern United States. The Nantucket pine tip moth, Rhyacionia frustrana (Comstock), in particular, often reduces growth of loblolly pine but has been difficult to control with traditional insecticides due to multiple annual generations and multi-year infestations which are difficult to predict in timing and location. Relatively new systemic insecticide products offer a solution in that their efficacy persists through multiple generations and years after a single application. Efficacy of systemic imidacloprid and fipronil were evaluated side by side across multiple sites in Virginia. Significant reductions in Nantucket pine tip moth damage were noted in trees treated with either the imidacloprid or fipronil product compared with check trees. After 2 yr, growth improvement of treated trees relative to controls was modest and not significant at all sites, but per acre volume indices were significantly greater in treated blocks as a result of higher tree survival. Reduced seedling mortality was attributed primarily to prevention of damage by pales weevil, Hylobius pales Herbst (Coleoptera: Curculionidae), by both insecticide treatments. Control of pales weevil in addition to pine tip moth suggests that systemic insecticide products with a long window of efficacy might control additional nontargeted pests.


Creatine supplementation--part I: performance, clinical chemistry, and muscle volume.
Our purpose was to study the effects and side effects of creatine (Cr) supplementation on high-intensity, short-term muscle work, on biochemical parameters related to Cr metabolism in blood and urine, and on muscle volume of the lower limb muscles. A cycling ergometer was used in a double-blind, cross-over study on 10 well-trained male physical education students to measure physical performance with 10 repetitive ergometer sprints (6-s duration, 30-s rest) before and after supplementation (5 d, 20 g x d(-1), washout period 61 +/- 8 d, mean +/- SEM, minimum 28 d) with Cr or placebo. Before and after supplementation, blood and urine were taken and the muscle volume of the lower limb was determined by magnetic resonance imaging (MRI). A significant (P << 0.05) increase in performance (+7%) at the end [4-6 s] of the later sprints (4-7 and 8-10) was observed combined with a lower production of blood lactate (-1 mmol x L(-1)) with Cr supplementation. The concentration of Cr was increased significantly in urine (P < 0.001) and serum (P = 0.005), whereas creatinine (Crn) was increased in serum (P < 0.001). Crn in urine and Crn clearance did not change significantly with Cr intake. There were no significant changes in the analyzed blood enzyme activities. A significant gain of body weight (pre-Cr 76.5 +/- 1.7 kg to 77.9 +/- 1.7 kg post-Cr) with Cr supplementation was measured, but no accompanying increase of muscle mass in a limited volume of the lower limb was observed by MRI. Cr supplementation is effective in improving short-term performance, and the methods used show no detrimental side effects with this supplementation protocol.


The central nervous system and HRT.
In postmenopausal women, both the aging process and the hypoestrogenism due to the loss of ovarian function seem to be related to the progressive impairment of cognitive functions and to a higher risk of developing Alzheimer's disease (AD). This paper reviews the potentially beneficial effects of hormonal replacement therapy (HRT) on cognition and on the risk of developing AD. Articles relevant to the topic were selected by reviewing MEDLINE data and references of previous published reviews on this subject. Epidemiological studies on the effects of HRT on cognitive functioning have yielded disparate results, perhaps because of varying methodology and designs. However, the available data suggest that the use of HRT could be associated with a lower risk for AD. This conclusion should be interpreted with caution, since most of the studies were case-control studies, and thus subjected to several sources of bias. Further well-designed and conducted clinical trials and longitudinal studies would be required to clarify the effects of estrogens on cognition and AD.


Tuning of Pectin Methylesterification: PECTIN METHYLESTERASE INHIBITOR 7 MODULATES THE PROCESSIVE ACTIVITY OF CO-EXPRESSED PECTIN METHYLESTERASE 3 IN A pH-DEPENDENT MANNER.
Pectin methylesterases (PMEs) catalyze the demethylesterification of homogalacturonan domains of pectin in plant cell walls and are regulated by endogenous pectin methylesterase inhibitors (PMEIs). In Arabidopsis dark-grown hypocotyls, one PME (AtPME3) and one PMEI (AtPMEI7) were identified as potential interacting proteins. Using RT-quantitative PCR analysis and gene promoter::GUS fusions, we first showed that AtPME3 and AtPMEI7 genes had overlapping patterns of expression in etiolated hypocotyls. The two proteins were identified in hypocotyl cell wall extracts by proteomics. To investigate the potential interaction between AtPME3 and AtPMEI7, both proteins were expressed in a heterologous system and purified by affinity chromatography. The activity of recombinant AtPME3 was characterized on homogalacturonans (HGs) with distinct degrees/patterns of methylesterification. AtPME3 showed the highest activity at pH 7.5 on HG substrates with a degree of methylesterification between 60 and 80% and a random distribution of methyl esters. On the best HG substrate, AtPME3 generates long non-methylesterified stretches and leaves short highly methylesterified zones, indicating that it acts as a processive enzyme. The recombinant AtPMEI7 and AtPME3 interaction reduces the level of demethylesterification of the HG substrate but does not inhibit the processivity of the enzyme. These data suggest that the AtPME3·AtPMEI7 complex is not covalently linked and could, depending on the pH, be alternately formed and dissociated. Docking analysis indicated that the inhibition of AtPME3 could occur via the interaction of AtPMEI7 with a PME ligand-binding cleft structure. All of these data indicate that AtPME3 and AtPMEI7 could be partners involved in the fine tuning of HG methylesterification during plant development.


Coagulopathy associated with superwarfarin exposure.
A female patient with significant coagulopathy is presented for case discussion. This case represented a presumed Munchausen exposure to commercially available rat poison that contained one of the superwarfarin chemicals, brodifacoum. Review of the medical literature is undertaken to discuss the diagnostic approach and treatment of superwarfarin exposure. The accidental or intentional exposure to this group of rodenticide represents a significant public health problem that often is not considered by primary care physicians when confronted with coagulopathy.


Voltage-insensitive Ca2+ channels and Ca2+/calmodulin-dependent protein kinases propagate signals from endothelin-1 receptors to the c-fos promoter.
Endothelin-1 (ET-1) triggers poorly understood nuclear signaling cascades that control gene expression, cell growth, and differentiation. To better understand how ET-1 regulates gene expression, we asked whether voltage-insensitive Ca2+ channels and Ca2+/calmodulin-dependent protein kinases (CaMKs) propagate signals from ET-1 receptors to the c-fos promoter in mesangial cells. Ca2+ influx through voltage-insensitive Ca2+ channels, one of the earliest postreceptor events in ET-1 signaling, mediated induction of c-fos mRNA and activation of the c-fos promoter by ET-1. A CaMK inhibitor (KN-93) blocked activation of the c-fos promoter by ET-1. Ectopic expression of CaMKII potentiated stimulation by ET-1, providing further evidence that CaMKs contribute to c-fos promoter activation by ET-1. The c-fos serum response element was necessary but not sufficient for CaMKII to activate the c-fos promoter. Activation of the c-fos promoter by ET-1 and CaMKII also required the FAP cis element, an AP-1-like sequence adjacent to the serum response element. Thus, voltage-insensitive Ca2+ channels and CaMKs apparently propagate ET-1 signals to the c-fos promoter that require multiple, interdependent cis elements. Moreover, these experiments suggest an important role for voltage-insensitive Ca2+ channels in nuclear signal transduction in nonexcitable cells.


When hearts, hands, and feet trump brains: centralist versus peripheralist responses in children and adults.
A series of studies examined the presence of centralist versus peripheralist responding about the physical location of psychological processes. Centralists respond that processes such as cognition and emotion are a function of the brain. Peripheralists respond that such processes are located in other parts of the body, such as the heart. Although peripheralist responses declined across grade levels, even older children and adults often gave peripheralist answers, depending on the context of the questions. Peripheralist responses occurred when participants were asked about the effect of switching irrelevant body parts between two people and when they were asked to choose a different body part among four choices. Results also showed adults' responses varied with different contextual cues. The findings support a coexistence model of development which argues for the simultaneous presence of developmentally advanced reasoning or scientifically based knowledge along with presumably less advanced, intuitive-based reasoning, or folk beliefs.


The axonal transport motor 'kinesin' is bound to anterogradely transported organelles: quantitative cytofluorimetric studies of fast axonal transport in the rat.
Monoclonal antibodies to the axonal transport ATPase kinesin were used in an immunofluorescent study on mammalian nerves. Following crushing of the sciatic nerve and the ventral roots of adult rats, immunoreactive material was found to accumulate rapidly, mainly proximal to a crush but also, to some degree, distal to a crush. The strongest immunofluorescence was observed after incubation with the H2 antibody against the heavy subunit of kinesin. Using the cytofluorimetric scanning (CFS) procedure, the accumulated amounts were quantified and it was found that the retrogradely accumulating kinesin-like immunoreactivity (IR) was about 4-12% of the anterogradely transported kinesin-IR. The results were compared to the vesicle marker p38 (synaptophysin), which was found to accumulate to a significant extent on both sides of the crush. Cytofluorimetric scanning measurements indicated that nearly 50% of the anterogradely accumulated p38-IR was recycling to the cell body. The results demonstrate that kinesin in the living axon is affiliated with anterogradely transported organelles. Retrogradely transported organelles appeared to carry very little kinesin-IR, suggesting that kinesin may be subject to turnover, distinct from that of p38, in the distal regions of the axon.


The effect of indium(III) triflate in oxone-mediated oxidative methyl esterification of aldehydes.
An oxidative methyl esterification of aldehydes was effectively achieved. The trivalent indium reagent, indium(III) triflate, was revealed to accelerate the reactions in many cases. Aromatic aldehydes with various substituents were subjected to this method, and each produced the corresponding methyl esters in good to excellent yields within a relatively short reaction time.


Multi-slice computed tomography-assisted endoscopic transsphenoidal surgery for pituitary macroadenoma: a comparison with conventional microscopic transsphenoidal surgery.
Intraoperative computed tomography (iCT) is a reliable method for the detection of residual tumour, but previous single-slice low-resolution computed tomography (CT) without coronal or sagittal reconstructions was not of adequate quality for clinical use. The present study evaluated the results of multi-slice iCT-assisted endoscopic transsphenoidal surgery for pituitary macroadenoma. This retrospective study included 30 consecutive patients with newly diagnosed or recurrent pituitary macroadenoma with supradiaphragmatic extension who underwent endoscopic transsphenoidal surgery using iCT (eTSS+iCT group), and control 30 consecutive patients who underwent conventional endoscope-assisted transsphenoidal surgery (cTSS group). The tumour volume was calculated by multiplying the tumour area by the slice thickness. Visual acuity and visual field were estimated by the visual impairment score (VIS). The resection extent, (preoperative tumour volume - postoperative residual tumour volume)/preoperative tumour volume, was 98.9% (median) in the eTSS+iCT group and 91.7% in the cTSS group, and had significant difference between the groups (P = 0.04). Greater than 95 and >90% removal rates were significantly higher in the eTSS+iCT group than in the cTSS group (P = 0.02 and P = 0.001, respectively). However, improvement in VIS showed no significant difference between the groups. The rate of complications also showed no significant difference. Multi-slice iCT-assisted endoscopic transsphenoidal surgery may improve the resection extent of pituitary macroadenoma. Multi-slice iCT may have advantages over intraoperative magnetic resonance imaging in less expensive, short acquisition time, and that special protection against magnetic fields is not needed.


Curative effect of crude exopolysaccharides of some macrofungi on alcohol-induced liver damage.
Abstract The authors investigate the curative effects of crude exopolysaccharides (EPS) produced by four Basidomycetes strains on the symptoms of alcoholic liver injury. EPSs were administered to experimental groups at levels of 100 mg per kg body weight per day for 7 days using an oral zonde needle after the onset of the disease. Serum levels of alanine transaminase (ALT), lactate dehydrogenase (LDH), DNA fragmentation, caspase-3 activities, and mitochondrial outer membrane integrity were determined following sacrifice of the rats. Light and transmission electron microscope (TEM) studies were performed on liver sections for histopathological and cytological evaluations. EPS that was obtained from Coprinus comatus OBCC 1014 decreased serum ALT level and increased outer membrane integrity, and allowed for the regaining of histologically and cytologically normal hepatocyte and tissue views. As a result, based on the obtained data, it can be argued that among all studied mushroom strains crude exopolysaccharides from Coprinus comatus OBCC 1014 strain have therapeutic potential for alcoholic liver injury according to control groups.


Withholding or withdrawing therapy in intensive care units: an analysis of collaboration among healthcare professionals.
The purpose of the study was to determine the views of intensive care nurses, intensivists, and primary physicians regarding collaboration and other aspects of withholding and withdrawing therapy in the intensive care unit (ICU). A questionnaire survey was conducted in seven hospitals in the Region of Southern Denmark, including six regional and four university ICUs. Four hundred ninety-five nurses, 135 intensivists, and 146 primary physicians participated in the study. The primary physicians came from two regional hospitals. The unified response rate was 84%. "Futile therapy" and "Patient's wish" were for all participants the main reasons for considering withholding or withdrawing therapy. Of primary physicians 63% found their general experience of collaboration very or extremely satisfactory compared to 36% of intensivists and 27% of nurses. Forty-three percent of nurses, 29% of intensivists, and 2% of primary physicians found that decisions regarding withdrawal of therapy were often, very often, or always unnecessarily postponed. Intensivists with ICU as their main workplace were more satisfied with the collaboration and more rarely found that end-of-life decisions were changed or postponed compared to intensivists who did not have ICU as their main workplace. Nurses, intensivists and primary physicians differ in their perception of collaboration and other aspects of withholding and withdrawing therapy practises at the ICU. Multi-disciplinary patient conferences, nurse involvement in the decision-making process, and guidelines for withholding and withdrawing therapy are recommended.


Role of intrastructural/intermolecular help in immunization with peptide-phospholipid complexes.
The design of effective subunit vaccines requires the inclusion of both B and T cell epitopes. The best mechanism for including both types of epitopes within an Ag is dependent upon how the Ag is processed by the APC for presentation to a responsive Th cell. If it is more efficient to process a single molecule for both helper and primary epitopes, than covalent linkage of B cells and T cell epitopes for intramolecular presentation of help would be recommended. If however, separate peptides containing either B or Th cell epitopes could be included within a single complex for the elicitation of intermolecular/intrastructural help, more antigenically diverse structures could be designed. This paper reports that it is possible to generate intermolecular/intrastructural help within an antigenic peptide-phospholipid (PL) complex. These peptide-PL complexes use well defined epitopes from Plasmodium falciparum as Ag. In addition to generating intrastructural help, we have shown that the Ir to these peptide-PL complexes is controlled by Ir genes and is similar to the Ir to the circumsporozoite protein of this pathogen.


Designing prevalence and incidence studies.
Frequency, impact, and causes of diseases--including wound development--can be examined using prevalence and incidence studies. Understanding basic epidemiologic principles is necessary to avoid misinterpretation of the data and incorrect translation of the results into clinical practice. Definitions and examples of prevalence, cumulative incidence, incidence rate, confidence intervals, and sample size are given. They will help practitioners comprehend these concepts and critically evaluate published research.


Chronic disease in the workplace and the environment. Lung disease: review of past initiatives.
The investigator working on OLD must realize that results may impact social, ethical, and moral issues and create economic dilemmas. This is different from most research endeavors which create warm appreciation for research findings. Finally, the researcher may be placed in an adversary position to argue or to extrapalate beyond the scientific findings which usually does not occur in research. Many are poorly equipped to deal with these issues, therefore confusion and distrust occasionally result. Working on OLD requires enormous understanding from the interested parties. Task force recommendations that fail to consider nonmedical and nonscientific needs for industry and labor are not likely to be welcomed or implemented.


Heterotropic pregnancy: a report of two cases.
Heterotropic pregnancy is reported infrequently in Nigeria. Two cases were managed within the span of five years with the successful delivery of a live term baby in one of the patients. A high clinical index of suspicion is required because an intra uterine gestation does not rule out a co-existing ectopic gestation especially in this region with high twinning rate and tubal disease


Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling.
Organoid technologies have become a powerful emerging tool to model liver diseases, for drug screening, and for personalized treatments. These applications are, however, limited in their capacity to generate functional hepatocytes in a reproducible and efficient manner. Here, we generated and characterized the hepatic organoid (eHEPO) culture system using human induced pluripotent stem cell (iPSC)-derived EpCAM-positive endodermal cells as an intermediate. eHEPOs can be produced within 2 weeks and expanded long term (>16 months) without any loss of differentiation capacity to mature hepatocytes. Starting from patient-specific iPSCs, we modeled citrullinemia type 1, a urea cycle disorder caused by mutations in the argininosuccinate synthetase (ASS1) enzyme. The disease-related ammonia accumulation phenotype in eHEPOs could be reversed by the overexpression of the wild-type ASS1 gene, which also indicated that this model is amenable to genetic manipulation. Thus, eHEPOs are excellent unlimited cell sources to generate functional hepatic organoids in a fast and efficient manner.


RNA folding during transcription.
The evolution of RNA sequence needs to satisfy three requirements: folding, structure, and function. Studies on folding during transcription are related directly to folding in the cell. Understanding RNA folding during transcription requires the elucidation of structure formation and structural changes of the RNA, and the consideration of intrinsic properties of the RNA polymerase and other proteins that interact with the RNA. This review summarizes the research progress in this area and outlines the enormous challenges facing this field. Significant advancement requires the development of new experimental methods and theoretical considerations in all aspects of transcription and RNA folding.


Design and fabrication of As2S3-based non-quarterwave multi-cavity Fabry-Perot filters with the laser-adjustable central wavelength.
We present a thorough study of the use of As2S3 thin films for the fabrication of high-performance multi-cavity bandpass filters. We show that such layers can be used inside a non-quarterwave multi-cavity Fabry-Perot structure to produce local changes of the central wavelength of the filter using photosensitive properties of this material. In particular, we study the impact of these index changes on the spectral performances of the filters and show how to adapt the design of the Fabry-Perot structures to produce a spectral shift without degrading the bandpass profile. Double- and three-cavity Fabry-Perot filters are theoretically and experimentally studied.


Prevention of human papilloma virus infection with vaccines.
Human Papilloma virus (HPV) is present in all the cases of cervical cancer. It can also cause other diseases like genital warts, condylomata accuminata, cervical intraepithelial neoplasia and Anogenital cancers. Cervical cancer is the second most common cause of death from cancer. To improve the mortality from cervical cancers it is extremely important to prevent the HPV infection. In this review we have discussed the role of HPV vaccines in preventing the HPV infections and so the cervical cancer.


Atypical adult-onset Still's disease with an initial and sole manifestation of liver injury: A case report and review of literature.
Adult-onset Still's disease (AOSD) typically presents with a high spiking fever, polyarthritis, transient maculopapular rash, neutrophilic leukocytosis, and hepatosplenomegaly. It has a wide spectrum of clinical symptoms ranging from mild to severe, with extensive involvement of almost every organ. Although liver involvement in the form of increased hepatic enzymes and bilirubin is common, no AOSD case with liver involvement as the initial manifestation of AOSD has been reported. A 35-year-old woman presented to the hepatology department with progressively worsening jaundice for one week. Liver chemistry tests revealed a significantly increased liver enzymes and bilirubin level. Given that the clinical examination was unremarkable, liver biopsy was considered because the patient had a history of AOSD 6 years ago. Liver histopathology revealed that most hepatic lobules were still recognizable. Fusional necrosis was observed around most central veins. A few bridging necrotic zones were also found. Infiltration of multiple plasma cells were observed in the necrotic zone, and the reticular scaffold was still expanded. Additionally, no obvious fibrosis was observed in the portal area. Mild mixed inflammatory cell infiltration was noted in the interstitium of the portal area. Further examination was unremarkable except for a remarkably high level of ferritin. Collectively, a presumptive diagnosis of liver injury secondary to AOSD was made. The hepatic involvement responded well to glucocorticoid treatment. This case highlights that hepatic involvement as an initial and sole manifestation could be a pattern of relapsed AOSD. The diagnosis of AOSD should be considered in the case of nonresolving liver injury after the exclusion of common etiologies for liver diseases. A liver biopsy can be useful for the differential diagnosis of liver injury associated with AOSD.


Characterization of Radish (Raphanus sativus) Storage Proteins.
Radish (Raphanus sativus cv Rond rose à bout blanc Vilmorin) seeds, as other cruciferae oil seeds, contain two major types of storage protein aggregates which can be separated by gel filtration into 12 and 1.7 Svedberg fractions. These two fractions have been characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, amino acid composition, and two bidimensional gel electrophoresis systems. These results were compared with those obtained with rapeseed storage proteins. Radish 12 Svedberg particles are made of a series of nine major polypeptides ranging from 33 to 30 kilodaltons. These polypeptides present charge heterogeneity. The 12 Svedberg particle is made of six subunits approximately 55 kilodaltons. Each subunit is a couple of two polypeptides linked by a disulfide bridge. The 1.7 Svedberg particle has a simpler composition. It is made of two polypeptides of 10 and 12 kilodaltons and smaller peptides of approximately 7 kilodaltons. Twelve and 1.7 Svedberg particles also differ in their amino acid composition, the 1.7 Svedberg being particularly rich in glutamic acid and proline. Its components are basic. The organization of the rapeseed storage protein is similar but more complex.


Reshaping a human antibody to inhibit the interleukin 6-dependent tumor cell growth.
The mouse PM-1 monoclonal antibody binds to the human interleukin 6 receptor, inhibits IL-6 functions, and shows strong antitumor cell activity against multiple myeloma cells. In order to be effective as a therapeutic agent administered to human patients in repeated doses, reshaped human PM-1 antibodies consisting of human REI-based light chain and NEW-based heavy chain variable regions were designed and constructed with the assistance of a structural model of the mouse PM-1 variable regions. The best reshaped human PM-1 antibody is equivalent to mouse or chimeric PM-1 antibody in terms of antigen binding and growth inhibition against multiple myeloma cells. Only a few minor changes in the human framework regions were required to recreate the mouse PM-1 antigen-binding site within a human antibody. The reshaped human PM-1 antibody, therefore, could be efficacious in human multiple myeloma patients.


[Research advances in identifying nitrate pollution sources of water environment by using nitrogen and oxygen stable isotopes].
Water body' s nitrate pollution has become a common and severe environmental problem. In order to ensure human health and water environment benign evolution, it is of great importance to effectively identify the nitrate pollution sources of water body. Because of the discrepant composition of nitrogen and oxygen stable isotopes in different sources of nitrate in water body, nitrogen and oxygen stable isotopes can be used to identify the nitrate pollution sources of water environment. This paper introduced the fractionation factors of nitrogen and oxygen stable isotopes in the main processes of nitrogen cycling and the composition of these stable isotopes in main nitrate sources, compared the advantages and disadvantages of five pre-treatment methods for analyzing the nitrogen and oxygen isotopes in nitrate, and summarized the research advances in this aspect into three stages, i. e. , using nitrogen stable isotope alone, using nitrogen and oxygen stable isotopes simultaneously, and combining with mathematical models. The future research directions regarding the nitrate pollution sources identification of water environment were also discussed.


Gene regulation by BCL3 in a cervical cancer cell line.
BCL3 is a putative proto-oncogene deregulated in haematopoieitic and solid tumours. It has been suggested that its oncogenic effects could be mediated, at least in part, by inducing proliferation and inhibiting cell death. To provide more insight into the mediators of these effects, we used an unbiased approach to analyse the mRNA expression changes after knocking-down BCL3 using specific shRNAs. One hundred eighty genes were up-regulated and sixtynine genes were down-regulated after knocking down BCL3. Function analyses showed enrichment in genes associated with cellular growth and proliferation, cell death and gene expression. We found that STAT3, an important oncogene in human cancer, was the central node of one of the most significant networks. We validated STAT3 as a bona fide target of BCL3 by additional interference RNA and in silico analyses of previously reported lymphoma patients.


Brain nicotinic acetylcholine receptors. Biochemical characterization by neosurugatoxin.
Specific [3H]nicotine binding to rat forebrain membranes was saturable and of high affinity, and it exhibited pharmacological specificity as well as stereoselectivity for nicotinic agents. There was a regional variation of specific [3H]nicotine binding in rat brain. Low concentrations of neosurugatoxin markedly inhibited specific [3H]nicotine binding in rat forebrain (IC50 = 78 nM) and the competition curve by the toxin was biphasic (pseudo-Hill slope, 0.44). Approximately 50% of [3H]nicotine binding in rat forebrain was inhibited by low concentrations (0.3-100 nM) of neosurugatoxin and the residual binding was inhibited by higher concentrations (0.3-10 microM). In the presence of 3 nM, 100 nM, and 1 microM neosurugatoxin, there was a concentration-dependent (28, 54, and 71%, respectively) loss of [3H]nicotine-binding sites (Bmax) in rat forebrain with little change in the dissociation constant (Kd). The blockade of brain [3H]nicotine-binding sites induced by neosurugatoxin was not reversed by washing. Further, the toxin (10 microM) considerably accelerated the dissociation of [3H]nicotine from its receptor sites initiated by nonlabeled (-)nicotine. These observations suggest that neosurugatoxin may allosterically regulate [3H]nicotine binding rather than competing directly. In contrast to a marked inhibition of [3H]nicotine binding, neosurugatoxin (100 nM-10 microM) had no effect on brain [3H]quinuclidinyl benzilate binding. In conclusion, the present study has shown that [3H]nicotine selectively labels nicotinic cholinergic receptors in rat brain and that neosurugatoxin is a potent noncompetitive antagonist of these receptors.


Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism.
Congenital hypogonadotropic hypogonadism (CHH) and its anosmia-associated form (Kallmann syndrome [KS]) are genetically heterogeneous. Among the >15 genes implicated in these conditions, mutations in FGF8 and FGFR1 account for ~12% of cases; notably, KAL1 and HS6ST1 are also involved in FGFR1 signaling and can be mutated in CHH. We therefore hypothesized that mutations in genes encoding a broader range of modulators of the FGFR1 pathway might contribute to the genetics of CHH as causal or modifier mutations. Thus, we aimed to (1) investigate whether CHH individuals harbor mutations in members of the so-called "FGF8 synexpression" group and (2) validate the ability of a bioinformatics algorithm on the basis of protein-protein interactome data (interactome-based affiliation scoring [IBAS]) to identify high-quality candidate genes. On the basis of sequence homology, expression, and structural and functional data, seven genes were selected and sequenced in 386 unrelated CHH individuals and 155 controls. Except for FGF18 and SPRY2, all other genes were found to be mutated in CHH individuals: FGF17 (n = 3 individuals), IL17RD (n = 8), DUSP6 (n = 5), SPRY4 (n = 14), and FLRT3 (n = 3). Independently, IBAS predicted FGF17 and IL17RD as the two top candidates in the entire proteome on the basis of a statistical test of their protein-protein interaction patterns to proteins known to be altered in CHH. Most of the FGF17 and IL17RD mutations altered protein function in vitro. IL17RD mutations were found only in KS individuals and were strongly linked to hearing loss (6/8 individuals). Mutations in genes encoding components of the FGF pathway are associated with complex modes of CHH inheritance and act primarily as contributors to an oligogenic genetic architecture underlying CHH.


Bag-Valve-Mask versus Laryngeal Mask Airway Ventilation in Cardiopulmonary Resuscitation with Continuous Compressions: A Simulation Study.
The 2017 International Liaison Committee on Resuscitation (ILCOR) guideline recommends that Emergency Medical Service (EMS) providers can perform cardiopulmonary resuscitation (CPR) with synchronous or asynchronous ventilation until an advanced airway has been placed. In the current literature, limited data on CPR performed with continuous compressions and asynchronous ventilation with bag-valve-mask (BVM) are available. In this study, researchers aimed to compare the effectiveness of asynchronous BVM and laryngeal mask airway (LMA) ventilation during CPR with continuous chest compressions. Emergency medicine residents and interns were included in the study. The participants were randomly assigned to resuscitation teams with two rescuers. The cross-over simulation study was conducted on two CPR scenarios: asynchronous ventilation via BVM during a continuous chest compression and asynchronous ventilation via LMA during a continuous chest compression in cardiac arrest patient with asystole. The primary endpoints were the ventilation-related measurements. A total of 92 volunteers were included in the study and 46 CPRs were performed in each group. The mean rate of ventilations of the LMA group was significantly higher than that of the BVM group (13.7 [11.7-15.7] versus 8.9 [7.5-10.3] breaths/minute; P <.001). The mean volume of ventilations of the LMA group was significantly higher than that of the BVM group (358.4 [342.3-374.4] ml versus 321.5 [303.9-339.0] ml; P = .002). The mean minute ventilation volume of the LMA group was significantly higher than that of the BVM group (4.88 [4.15-5.61] versus 2.99 [2.41-3.57] L/minute; P <.001). Ventilations exceeding the maximum volume limit occurred in two (4.3%) CPRs in the BVM group and in 11 (23.9%) CPRs in the LMA group (P = .008). The results of this study show that asynchronous BVM ventilation with continuous chest compressions is a reliable and effective strategy during CPR under simulation conditions. The clinical impact of these findings in actual cardiac arrest patients should be evaluated with further studies at real-life scenes.


Anterior Knee Pain and Oedema-like Changes of the Suprapatellar Fat Pad: Correlation of the Symptoms with MRI Findings.
The aetiology of anterior knee pain is multifactorial, and any patellofemoral structure can be the cause of the symptoms. For the last decades, the suprapatellar fat pad is studied as a potential cause of anterior knee pain. Since the results in the literature are contradictory, in this study, we tried to reevaluate the role of the suprapatellar fat pad in the development of anterior knee pain. Total 156 knee MRIs of 150 patients from December 2015 to July 2019 were retrospectively evaluated by a radiologist for the configuration of the suprapatellar fat pads. The population was divided into two groups according to the presence of anterior knee pain. Maximum craniocaudal, anteroposterior and oblique diameters, and relative signal intensity indexes of the suprapatellar fat pads were measured and compared between the groups. Configurations of the fat pads were recorded, and measurements of the triangular-shaped and convex posterior bordered suprapatellar fat pads were compared. A student t-test was used for statistical analysis. Statistically, significant differences and correlations were defined as p<0.05. The diameters and relative signal intensity indexes of the fat pads showed no significant difference between the groups (p=0.588, 0.744, 0.874, and 0.201, respectively). Anteroposterior and oblique diameters and relative signal intensity indexes of the suprapatellar fat pads were correlated with the convex posterior border (p=0.001, 0.003, and 0.000, respectively). Oedema-like changes of the suprapatellar fat pad seen at knee MRIs are correlated with the configuration of the fat pad but are rarely associated with anterior knee pain.


Citric Acid cycle activity in mitochondria isolated from mung bean hypocotyls.
Citric acid cycle activity in mitochondria from mung bean (Phaseolus aureus var. Jumbo) hypocotyls were examined by surveying (a) characteristics of oxidation of cycle intermediates; (b) activities of cycle enzymes in mitochondrial extracts; (c) contents of cycle intermediates and electron transport components in isolated mitochondria; and (d) time-course changes of products formed during oxidation of succinate, malate, and citrate. Isolated mitochondria are deficient in thiamine pyro-phosphate and somewhat so in adenylates, but apparently sufficient in CoA, NAD, and electron transport carriers. Cycle activity in the mitochondria is not directly correlated with the activities of the enzymes measured in extracts. These studies led to the conclusion that the region between malate and citrate is an important regulatory area in citric acid cycle functioning in isolated mung bean mitochondria.


Heart rate variability analysis during muscle fatigue due to prolonged isometric contraction.
Fatigue can be defined as the muscular condition occurring before the inability to perform a task. It can be assessed through the evaluation of the median and mean frequency of the spectrum of the surface electromyography series. Previous studies investigated the relationship between heartbeat dynamics and muscular activity. However, exploitation of such cardiovascular measures to automatically identify muscle fatigue during fatiguing exercises is still missing. To this extent, HRV signals were gathered from 32 subjects during an isometric contraction task, and features defined in the time, frequency and nonlinear domains were investigated. We used surface electromyography to label the occurrence of muscle fatigue. Statistically significant differences were observed by comparing features related to fatigued subjects with the non-fatigued ones. Moreover, a pattern recognition system capable to achieve an average accuracy of 78.24% was implemented. These results confirmed the hypothesis that a relationship between heartbeat dynamics and muscle fatigue might exist.


IFN regulatory factor 5 is required for disease development in the FcgammaRIIB-/-Yaa and FcgammaRIIB-/- mouse models of systemic lupus erythematosus.
Polymorphisms in the transcription factor IFN regulatory factor 5 (IRF5) are strongly associated in human genetic studies with an increased risk of developing the autoimmune disease systemic lupus erythematosus. However, the biological role of IRF5 in lupus pathogenesis has not previously been tested in an animal model. In this study, we show that IRF5 is absolutely required for disease development in the FcgammaRIIB(-/-)Yaa and FcgammaRIIB(-/-) lupus models. In contrast to IRF5-sufficient FcgammaRIIB(-/-)Yaa mice, IRF5-deficient FcgammaRIIB(-/-)Yaa mice do not develop lupus manifestations and have a phenotype comparable to wild-type mice. Strikingly, full expression of IRF5 is required for the development of autoimmunity, as IRF5 heterozygotes had dramatically reduced disease. One effect of IRF5 is to induce the production of the type I IFN, IFN-alpha, a cytokine implicated in lupus pathogenesis. To address the mechanism by which IRF5 promotes disease, we evaluated FcgammaRIIB(-/-)Yaa mice lacking the type I IFN receptor subunit 1. Unlike the IRF5-deficient and IRF5-heterozygous FcgammaRIIB(-/-)Yaa mice, type I IFN receptor subunit 1-deficient FcgammaRIIB(-/-)Yaa mice maintained a substantial level of residual disease. Furthermore, in FcgammaRIIB(-/-) mice lacking Yaa, IRF5-deficiency also markedly reduced disease manifestations, indicating that the beneficial effects of IRF5 deficiency in FcgammaRIIB(-/-)Yaa mice are not due only to inhibition of the enhanced TLR7 signaling associated with the Yaa mutation. Overall, we demonstrate that IRF5 plays an essential role in lupus pathogenesis in murine models and that this is mediated through pathways beyond that of type I IFN production.


Vermicomposting of a lignocellulosic waste from olive oil industry: a pilot scale study.
The vermicomposting with Eisenia andrei of dry olive cake, a lignocellulosic waste produced during the extraction of olive oil, either alone or mixed with municipal biosolids, was studied in a nine-month pilot scale experiment. Number and biomass of earthworms and enzyme activities were periodically monitored and relevant properties of the final products were determined. In the assayed substrates, the total biomass of earthworms increased at the end of the experimental period between 9 and 12-fold respectively in comparison with the earthworm biomass initially inoculated. The increase in hydrolytic enzymes and overall microbial activity during the vermicomposting process indicated the biodegradation of the olive cake and resulted in the disappearance of the initial phytotoxicity of the substrate. However, the recalcitrant lignocellulosic nature of the dry olive cake prevented suitable humification during the vermicomposting process. For this reason, in addition to organic amendments, other management procedures should be considered.


Pharmacoeconomics of schizophrenia in the 21st century.
During the next century-if not before-a variety of issues associated with mental health care in the United States need to be addressed and resolved nationwide, including securing full parity for patients with psychiatric disorders, improving the overall medical health of psychiatric patients, establishing the effectiveness as well as the efficacy of new drugs and educating health care providers about new drugs and new uses for older drugs, and using all costs to evaluate new therapeutic strategies or medications. The following discussion covers some of the major findings from studies conducted in the Commonwealth of Massachusetts, touches on some of the areas mentioned above, and is intended to serve as a springboard for exchanges among professionals in the health care community who care for psychiatric patients.


[A case of Down's syndrome associated with recurrent testicular tumor treated by chemotherapy successfully: review of 41 cases in Japanese literature].
A 35-year-old male patient with Down' s syndrome received radical inguinal orchitectomy for left testicular tumor in 2006. Histological examination revealed a typical seminoma. 18 months after the operation, we found a metastasis in the right retroperitoneum lymph node. He received adjuvant chemotherapy (bleomycin, etoposide, and cisplatin : BEP). After 3 cycles of chemotherapy, the tumor disappeared. There is no obvious re-occurrence sign and general condition is good after chemotherapy. As we treated a relapse of seminoma in Down's syndrome successfully, we report this case and review 41 cases in Japanese literatures.