Diagnosis of pericardial effusion by computed tomography.
We assessed the diagnostic utility of computed tomography (CT) in the detection of pericardial effusion by using a dog model in which the amount and type of pericardial fluid were controlled and by obtaining CT scans on patients with suspected pericardial effusion prior to pericardiocentesis. The experimental studies showed that CT was capable of detecting pericardial effusion composed of serous fluid or saline in amounts as small as 50 ml. However, the hemopericardium was radiographically isodense with the heart and difficult to detect by CT unless the epicardial fat pad was identified or intravenous contrast enhancement of the heart was used. CT clearly demonstrated the presence of pericardial effusion in all six patients studied prior to successful pericardiocentesis or pericardiectomy. We conclude that CT is a sensitive noninvasive method which can be used for the diagnosis of pericardial effusion.


Effects of Short- and Medium-Chain Fatty Acids on Production, Meat Quality, and Microbial Attributes-A Review.
The non-therapeutic use of antimicrobials in poultry production contributes to the spread of drug-resistant pathogens in both birds and humans. Antibiotics are known to enhance feed efficiency and promote the growth and weight gain of poultry. New regulatory requirements and consumer preferences have led to a reduced use of antibiotics in poultry production and to the discovery of natural alternatives to antibiotic growth promoters. This interest is not only focused on the direct removal or inhibition of causative microorganisms but also on the prevention of diseases caused by enteric pathogens using a range of feed additives. A group of promising feed additives is composed of short- and medium-chain fatty acids (SCFAs and MCFAs) and their derivatives. MCFAs possess antibacterial, anticoccidial, and antiviral effects. In addition, it has been proven that these acids act in synergy if they are used together with organic acids, essential oils, or probiotics. These fatty acids also benefit intestinal health integrity and homeostasis in broilers. Other effects have been documented as well, such as an increase in intestinal angiogenesis and the gene expression of tight junctions. The aim of this review is to provide an overview of SCFAs and MCFAs as alternatives to antibiotic growth promoters and to summarize the current findings in the literature to show their possible benefits on production, meat quality, and gut health in poultry.


Transient Magnetophotoinduced Absorption Studies of Photoexcitations in π-Conjugated Donor-Acceptor Copolymers.
We have utilized a plethora of transient and steady state optical and magneto-optical spectroscopies in a broad spectral range (0.25-2.5 eV) for elucidating the primary and long-lived photoexcitations in a low band-gap π-conjugated donor-acceptor (DA) copolymer used for efficient photovoltaic solar cells. We show that both singlet excitons (SE) and intrachain triplet-triplet (TT) pairs are photogenerated in the DA-copolymer chains. From the picosecond transient magnetic field response of these species we conclude that the SE and TT spin states are coupled. The TT decomposition into two intrachain geminate triplet excitons maintains spin coherence and thus their spin entanglement lasts into the microsecond time domain.


Validity in diagnosing osteoporosis. Observer variation in interpreting spinal radiographs.
Observer variation in interpreting radiograph of the spine in 70-year-old Danish women has been examined. The women joined a general health investigation as part of an epidemiologic screening for osteoporosis. Two experienced radiologists examined independently 280 sets of lateral radiographs of the spine to disclose fractures. The radiographs were examined four times, each examined at two different occasions by each radiologist. Overall intra-observer agreement was 88% and 87% when asked for presence or absence of fractures, irrespective of fracture localization. When accidental occurrence of agreement was taken into account (kappa analysis) intra-observer variation was reduced to 64% and 62%. The overall inter-observer agreement was 75%, but reduced to 47% when accidental occurrence of agreement was noted. Kappa analysis in testing observer variation indicates that a considerable part of agreement can be ascribed to chance alone. This seriously questions the hitherto used definition of osteoporosis.


Incorporating Comprehensive Management of Direct Oral Anticoagulants into Anticoagulation Clinics.
Anticoagulation clinics emerged as a means to optimize warfarin effectiveness and minimize bleeding risks. Anticoagulation clinics have traditionally been warfarin-based models due to the need for frequent blood-level monitoring, drug interactions, dietary considerations, and periprocedural management with warfarin. These models have demonstrated improved anticoagulation control and reduced bleeding complications for patients taking warfarin. Direct oral anticoagulants (DOACs) emerged with the perception of improved convenience due to the lack of blood-level monitoring and lack of dietary considerations. Despite the advantages of DOAC therapy, new challenges exist with their management, warranting ongoing monitoring. Such challenges include prescribing and dosing issues, drug adherence, drug interactions, and high drug cost. Comprehensive anticoagulation centers are needed to manage and monitor all oral anticoagulants including DOACs. The objectives of this review are to describe the challenges and opportunities that exist in the management of DOACs and to describe a practice model that integrates a DOAC management service into the traditional anticoagulation clinic.


Metabolite profiling of "green" extracts of Corylus avellana leaves by 1H NMR spectroscopy and multivariate statistical analysis.
Corylus avellana L. (Betulaceae) leaves, consumed as infusion, are used in traditional medicine, for the treatment of hemorrhoids, varicose veins, phlebitis, and edema due to their astringent, vasoprotective, and antiedema properties. In previous works we reported from the leaves of Corylus avellana cv. "Tonda di Giffoni" diarylheptanoid derivatives, a class of plant secondary metabolites with a wide variety of bioactivities. With the aim to give an interesting and economically feasible opportunity to C. avellana leaves as source of functional ingredients for pharmaceutical and cosmetic formulations, "green" extracts were prepared by employing "eco-friendly" extraction protocols as maceration, infusion and SLDE-Naviglio extraction. Metabolite profiles of the extracts were obtained by 1H NMR experiments and data were processed by multivariate statistical analysis to highlight differences in the extracts and to evidence the extracts with the highest concentrations of bioactive metabolites. Based on the NMR data, a total of 31 compounds were identified. The metabolite variation among the extracts was evaluated using Principle Component Analysis (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA). Furthermore, the total phenolic content of the extracts was measured by Folin-Ciocalteu colorimetric assay and the antioxidant activity of extracts was assayed by the spectrophotometric tests DPPH• and ABTS and by an in vitro test based on the evaluation of cellular reactive oxygen species production stimulated by pyocyanin.


PKA-I holoenzyme structure reveals a mechanism for cAMP-dependent activation.
Protein kinase A (PKA) holoenzyme is one of the major receptors for cyclic adenosine monophosphate (cAMP), where an extracellular stimulus is translated into a signaling response. We report here the structure of a complex between the PKA catalytic subunit and a mutant RI regulatory subunit, RIalpha(91-379:R333K), containing both cAMP-binding domains. Upon binding to the catalytic subunit, RI undergoes a dramatic conformational change in which the two cAMP-binding domains uncouple and wrap around the large lobe of the catalytic subunit. This large conformational reorganization reveals the concerted mechanism required to bind and inhibit the catalytic subunit. The structure also reveals a holoenzyme-specific salt bridge between two conserved residues, Glu261 and Arg366, that tethers the two adenine capping residues far from their cAMP-binding sites. Mutagenesis of these residues demonstrates their importance for PKA activation. Our structural insights, combined with the mutagenesis results, provide a molecular mechanism for the ordered and cooperative activation of PKA by cAMP.


Abstracting deficits and childhood conduct disorder as a function of familial alcoholism.
Using a large sample (n = 515), family history-positive male alcoholics (FH+) performed poorer than family history-negative (FH-) alcoholics on a test of abstracting ability. They also reported an earlier age of onset of alcoholism, more symptoms of childhood conduct disorder, and tended to report more depressive symptoms than FH- alcoholics, however, these variables were not significantly related to abstracting score. FH+ and FH- samples did not differ on average amount of ethanol consumed per day, vocabulary, state anxiety, childhood attentional deficit disorder, and childhood learning disability. The significant differences found in this study between FH+ and FH- alcoholics were minimal. With such weak effects, the inconsistent findings in studies that have investigated differences between FH+ and FH- alcoholics are understandable.


Protocol for performing nephrological activity in the Republic of Macedonia.
The fast development of nephrology in the world, especially in the second half of the 20 th century demanded protocol (guidelines) for nephrological activity for all levels of medical care, of doctors and specialists. The International Society of Nephrology, the European Renal Association and other national associations created their own protocol (guidelines) for nephrological activity. The Macedonian Society of Nephrology, Dialysis, Transplantation and Artificial Organs (MSNDTAO) proclaimed the First Protocol for Performing Nephrological Activity in the Republic of Macedonia at the First Congress of the MSNDTAO, held in Ohrid 1993, and it was published in the Macedonian Medical Review, 1994; Supplement 14: 397-406 [1]. The update of the Protocol for Performing Nephrological Activity in the Republic of Macedonia was proclaimed at the Fourth Congress of MSNDTAO, held in Ohrid 2012 and it presented in this text.


Non-human papillomavirus penile squamous cell carcinoma with unusual coral-like polymorphic lesion.
Penile cancer is a rare malignancy of the male genital system. Approximately 98% of penile cancer corresponds to squamous cell carcinoma (SCC), with further morphological and molecular classification into human papillomavirus (HPV) dependent and non-HPV SCC. Compared to HPV-induced SCC, non-HPV SCC appeared to have a worse prognosis. Here, we present a case of an uncircumcised male with an unusual coral-like polymorphic lesion, and confirmed histopathology of well-differentiated non-HPV penile SCC with rapid growth progression.


Comprehensive phosphoproteome analysis in rice and identification of phosphoproteins responsive to different hormones/stresses.
Phosphoproteins in rice were detected by in vitro protein phosphorylation followed by two-dimensional polyacrylamide gel electrophoresis. Forty-four phosphoproteins were detected on a 2D-gel after in vitro protein phosphorylation of the crude extract from rice leaf sheath. Among the phosphoproteins detected, 42 were identified through analysis by Q-TOF MS/MS and/or MALDI-TOF MS. The largest percentage of the identified phosphoproteins are involved in signaling (30%), while 18% are involved in metabolism. When rice seedlings were treated with various hormones and stresses, it was observed that the phosphorylation of 13 proteins was enhanced differentially by different hormone and stress treatments. Furthermore, when the hormone/stress regulated phosphoproteins are compared in rice leaf sheath, leaf blade and root, only cytoplasmic malate dehydrogenase was found to be phosphorylated in all the tissues. Results suggest that in the phosphorylation cascade of rice, glycolytic metabolism processes and Ca(2+)-signaling seem to be important targets in response to hormones and stresses. Furthermore, the direct visualization of phosphoproteins by (32)P-labeling and their mass spectrometric identification provides an accurate and reliable method of analyzing the rice phosphoproteome.


Colloidal pen lithography.
Colloidal pen lithography, a low-cost, high-throughput scanning probe contact printing method, has been developed, which is based on self-assembled colloidal arrays embedded in a soft elastomeric stamp. Patterned protein arrays are demonstrated using this method, with a feature size ranging from 100 nm to several micrometers. A brief study into the specificity reorganization of protein gives evidence for the feasibility of this method for writing protein chips.


Fungal aneurysms of intracranial vessels.
Intracranial fungal aneurysms arise from major cerebral arteries. Fungi directly invade vessel walls from the luminal surface (fungal emboli) or from the adventitia (fungal meningitis). The vasa vasorum are free of fungi. Aneurysmal rupture is common with extensive hemorrhagic necrosis of the surrounding brain. Aspergillus is the usual causative agent; its sources are nasal sinusitis or endocarditis.


Atypical fibroxanthoma: a selective review.
The head and neck area has disproportionate number of cutaneous tumors given the surface area, as compared with the rest of the body. Many of the tumors are related to chronic actinic damage and the most common by far are squamous and basal cell carcinomas. Atypical fibroxanthoma refers to a group of usually indolent cutaneous tumors that occur in older adults and are characterized histologically by a population of fusiform, epithelioid, and pleomorphic cells, numerous cells in mitosis, and intracytoplasmic lipidization in some cells. Numerous histologic variants have been described, including a clear-cell, desmoplastic or keloidal, granular, angiomatoid, hemosiderotic, and myxoid, among others. These tumors have a mesenchymal immunophenotype. Some authors believe that atypical fibroxanthoma is a dedifferentiated variant of squamous cell carcinoma. We present a review of this particular neoplasm with special emphasis on the histomorphology, subtypes, immunophenotypic profile, and discussion of differential diagnosis.


Decreased mortality in patients prescribed vancomycin after implementation of antimicrobial stewardship program.
The impact of an antimicrobial stewardship program (ASP) on 30-day mortality rates was evaluated in patients prescribed vancomycin in a Veterans Affairs hospital. A retrospective chart review of patients receiving a minimum of 48 hours of vancomycin during October 2006-July 2014. A multivariate logistic regression analysis was used to determine predictors of mortality. Interventions of the ASP consist of appropriate antibiotic selection, dosing, microbiology, and treatment duration. Death occurred in 12.4% of 453 patients. Of the 56 deaths, 64.3% occurred during prestewardship versus 35.7% during stewardship (P = .021). Increased mortality was associated with pre-ASP (odds ratio [OR], 2.17; 95% confidence interval [CI], 1.13-4.27), age (unit OR, 1.08; 95% CI, 1.05-1.12), nephrotoxicity (OR, 3.24; 95% CI, 1.27-8.01), and hypotension (OR, 3.28; 95% CI, 1.42-7.44). Patients treated in the intensive care unit were associated with increased mortality. Patients in the stewardship group experienced lower rates of mortality, which may be caused by interventions initiated by the stewardship team, including minimizing nephrotoxicity and individualized chart review. Mortality in patients treated with vancomycin was decreased after antimicrobial stewardship was implemented. As anticipated, older age, hypotension, nephrotoxicity, and intensive care unit admission were associated with an increased incidence of mortality.


Platycodin D induces tumor growth arrest by activating FOXO3a expression in prostate cancer in vitro and in vivo.
Platycodin D (PD), a major saponin derived from Platycodin grandiflorum, exerted cytotoxicity against prostate cancer cell lines (PC3, DU145 and LNCaP cells) with IC₅₀ values in the range of 11.17 to 26.13 μmol/L, whereas RWPE-1 cells (a non-malignant human prostate epithelial cell line) were not significantly affected. A further study in these cell lines showed that PD could potently affect cell proliferation (indicated by the bromodeoxyuridine assay), induce cell apoptosis (determined by Annexin V-FITC flow cytometry) and cause cell cycle arrest (indicated by PI staining). After being treated with PD for 48 hours, DU145 and LNCaP cells were arrested in the G0 /G1 phase, and PC3 cells were arrested in the G2/M phase. A Western blotting analysis indicated that PD increased the expression of the FOXO3a transcription factor, decreased the expression of p-FOXO3a and MDM2 and increased the expression of FOXO-responsive genes, p21 and p27. MDM2 silencing (transiently by siRNA-MDM2) increased the PD-induced FOXO3a protein expression, while MDM2 overexpression (in cells transiently transfected with a pcDNA3-MDM2 plasmid) decreased the PD-induced expression of the FOXO3a protein. Moreover, PD dose-dependently inhibited the growth of PC3 xenograft tumors in BALB/c nude mice. A Western blotting analysis of the excised xenograft tumors indicated that similar changes in protein expression also occurred in vivo. These results suggest that PD exhibits significant activity against prostate cancer in vitro and in vivo. The FOXO3a transcription factor appears to be involved in the activity of PD. Together, all of these findings provide a basis for the future development of this agent for human prostate cancer therapy.


Aggressive multilocular osteoblastoma in the mandible: a rare and difficult case to diagnose.
Osteoblastoma is a benign neoplasia and is uncommon in the jaws. In some cases, this lesion presents extremely aggressive local characteristics and is termed aggressive osteoblastoma. Because the clinical, radiographic and histopathologic characteristics are similar to those of a variety of benign and malignant tumors, it poses a diagnostic dilemma. This report presents a case of an aggressive osteoblastoma in the mandible and discusses the differential diagnosis of this lesion. A 13-year-old white male sought the Stomatology Clinic at the State University of Paraíba, Campina Grande, PB, Brazil, complaining of asymptomatic swelling on the left side of his face. Cone-beam computerized tomography showed a multilocular, hypodense bone lesion, located in the body of the left mandible and lower third of the ascending ramus. The initial diagnostic hypothesis was juvenile ossifying fibroma or osteosarcoma. After histopathologic examination, the final diagnosis was aggressive osteoblastoma. Surgical resection with a safety margin was performed. There was no evidence of recurrence after a follow-up period of 4 years.


Sphingomonas Paucimobilis: A Rare Infectious Agent Found in Cerebrospinal Fluid.
Sphingomonas paucimobilis (S. paucimobilis) is a gram negative bacillus. It has existed in soil, drinking water and plants. It has been isolated from distilled water tanks, respirators, and hemodialysis devices at the hospital setting. Patients with chronic disorders or immune suppression may be susceptible to infections with it. This microorganism has also been reported to infect healthy persons. Both nosocomial and community-acquired infections have been reported. So far, a variety of infections have been reported, including sepsis, septic pulmonary embolism, septic arthritis, peritonitis, and endophthalmitis. Only 2 cases of meningitis have been reported so far in the literature. So far, no previous reports of culture proliferation have been reported in patients with external ventricular drains, as was the case in our patient. Therefore, our case is the first to have S. paucimobilis proliferation in cerebrospinal fluid culture during intensive care unit stay for an external ventricular drain.


Application of Elastic Traction Band Combined with Pain Assessment in Elderly Patients After Hip Replacement.
This study aims to investigate the use of an elastic traction band in conjunction with pain evaluation in geriatric patients after hip replacement. Eighty hip arthroplasty cases involving senior patients at our institution were chosen for this study, covering the period from February 2021 to January 2022. They were separated into the control and observation groups using the premise of comparing and contrasting the two groups' shared fundamental characteristics. Traditional nursing care was given to the control group, while the observation group got an elastic stretch traction belt and pain assessment nursing care. The application effect of the two groups was observed. Before surgery, there was no statistically significant difference in the Harris hip function score between the two groups (P > .05). Harris scores for research items in both groups improved 6 months after surgery, compared to scores obtained before surgery (P < .05), and the increase was greater in the observation group than in the control group (P < .05). Self-efficacy for physical activity, coping, and the overall SER scale were all greater in the observation group than in the control group (P < .05). There was no statistically significant difference between the two groups on any measure of material wellbeing (P > .05). Mental and physical health scores were better in the observation group than in the control group (P < .05). Patients' social dimensions were compared to those of two control groups, and the results showed no statistically significant difference in terms of social function aspects (P > .05), although the control group reported much lower levels of enjoyment, learning, and work, the observation group reported significantly greater levels (P < .05). Patient treatment compliance study using a rank sum test revealed that the observation group's postoperative exercise compliance was considerably greater than that of the control group. Observation group members were more compliant than control group members, with an average rank of 30.829 compared to 40.171 for both groups (P < .05). Patients who have had hip arthroplasty may benefit from using an elastic traction belt in conjunction with pain assessment to increase the likelihood that they would participate in rehabilitation exercises, so enhancing their self-efficacy, hip function, and quality of life.


[Lesion of extrahippocampal cortices of left medial temporal lobe: a case report].
The cortex of medial temporal lobe is a group of different allocortical fields which included the hippocampal formation (dentate gyrus, hippocampus proper, and subicular complex) and extrahippocampal cortices (entorhinal, perirhinal, and parahippocampal). It is widely accepted that both of them play an important role in memory process. In humans, several reports indicates that damage to the hippocampus alone would lead to a clinically significant amnesia; when the injuries are more extensive others cognitive disorders, as those related to visual sphere, make worse the clinic picture, and some of these cases were reported as associative visual agnosias. Nevertheless, although evidence from animal studies points to the importance of the extrahippocampal medial temporal lobe cortices in order to recognise visual stimuli, such involvement has not been demonstrated in humans. A 44 year-old male who consulted us because they had lost about of '80% of his vision' after a stroke. Ophthalmological examination was entirely within normal limits, but neuropsychological test put in evidence difficulties in the visuo-verbal naming, discrimination of superposed images, recognition of faces and, mainly, in the test of immediate and deferred visual memory. Anterograde memory impairment was also revealed. Magnetic resonance imaging showed a lesion of left entorhinal, perirhinal and parahippocampal cortices. We suggest, in relation to anatomical evidences, that isolation of hippocampus is responsible for symptomatollogy of our patient.


Inpatient applications of cognitive-behavioral therapy : a review of recent developments.
The authors review empirical research of the past decade on cognitive-behavioral therapy (CBT) in the treatment of depressed inpatients and offer suggestions for future investigations. CBT appears to offer additive benefits in combination with pharmacotherapy, particularly after the transition from inpatient to outpatient treatment. CBT also holds promise as a primary treatment for inpatients but has not been clearly shown to be as effective as antidepressants. There is as yet no evidence that inpatient CBT is superior to other psychotherapies of comparable intensity or that short-term inpatient CBT has enduring value if not followed by outpatient therapy. Further research is needed to clarify the specific effects of CBT for inpatients and to establish its cost-effectiveness.


The efficacy of manual toothbrushes following a brushing exercise: a systematic review.
To determine the efficacy of manual tooth brushing with respect to toothbrush design and brushing duration. The PubMed-MEDLINE and Cochrane CENTRAL were searched through October 2010 to identify appropriate studies. The outcome measurement was dental plaque removal following subject brushing. The search yielded 2119 titles and abstracts. Ultimately, 59 papers with 212 brushing exercises as separate legs of the experiments and meeting the eligibility criteria were selected. Overall, a brushing exercise provides a 42% (21) plaque score reduction (95% CI: 41.23; 42.03). Of the brushing studies providing data as assessed according to the Quigley and Hein plaque index, the weighted mean reduction from baseline in plaque scores was 30% (95% CI: 26.79; 33.21). A weighted mean plaque score reduction of 53% (95% CI: 49.51; 56.49) was observed in the experiments using the Navy plaque index. Subanalysis between the different bristle tuft configurations illustrated variation in plaque removal ability (24-61%). The angled bristle design numerically showed the highest mean plaque reduction with either index. A subanalysis of brushing duration revealed after 1 min, a mean reduction of 27% and after 2 min, 41%. The efficacy in plaque removal following a brushing exercise is a reduction from baseline plaque scores of 42% on average, with a variation of 30-53% dependent on the plaque index used. The available evidence indicates that bristle tuft arrangement (flat trim, multilevel, angled) and brushing duration are factors that contribute to the variation in observed efficacy.


microRNA, Cancer and Cancer Chemoprevention.
microRNA(miRNA) is a kind of non-coding RNA that has a regulatory function on coding miRNA. miRNA can target the 3 UTR of mRNA and inhibit its gene expression by either inhibiting its translation or promoting its degradation. miRNAs are thus considered to be oncogenic or antineoplastic, depending on their downstream target mRNAs. Besides their clinical application in cancer treatment, diagnosis, and prognosis, miRNA has also recently been reported to be involved in cancer chemotherapy and chemoprevention. This review focuses on the implication of miRNA in cancer chemoprevention and cancer control as well as molecular mechanisms underlying those biological effects.


Bioinspired Luminescent Europium-Based Probe Capable of Discrimination between Ag+ and Cu.
Due to their similar coordination properties, discrimination of Cu+ and Ag+ by water-soluble luminescent probes is challenging. We have synthesized LCC4Eu, an 18 amino acid cyclic peptide bearing a europium complex, which is able to bind one Cu+ or Ag+ ion by the side chains of two methionines, a histidine and a 3-(1-naphthyl)-l-alanine. In this system, the naphthyl moiety establishes a cation-π interaction with these cations. It also acts as an antenna for the sensitization of Eu3+ luminescence. Interestingly, when excited at 280 nm, LCC4Eu behaves as a turn-on probe for Ag+ (+150% Eu emission) and as a turn-off probe for Cu+ (-50% Eu3+ emission). Shifting the excitation wavelength to 305 nm makes the probe responsive to Ag+ (+380% Eu3+ emission) but not to Cu+ or other physiological cations. Thus, LCC4Eu is uniquely capable of discriminating Ag+ from Cu+. A detailed spectroscopic characterization based on steady-state and time-resolved measurements clearly demonstrates that Eu3+ sensitization relies on electronic energy transfer from the naphthalene triplet state to the Eu3+ excited states and that the cation-π interaction lowers the energy of this triplet state by 700 and 2400 cm-1 for Ag+ and Cu+, respectively. Spectroscopic data point to a modulation of the efficiency of the electronic energy transfer caused by the differential red shift of the naphthalene triplet, deciphering the differential luminescence response of LCC4Eu toward Ag+ and Cu+.


Mothers' Attachment Representations and Children's Brain Structure.
Ample research demonstrates that parents' experience-based mental representations of attachment-cognitive models of close relationships-relate to their children's social-emotional development. However, no research to date has examined how parents' attachment representations relate to another crucial domain of children's development: brain development. The present study is the first to integrate the separate literatures on attachment and developmental social cognitive neuroscience to examine the link between mothers' attachment representations and 3- to 8-year-old children's brain structure. We hypothesized that mothers' attachment representations would relate to individual differences in children's brain structures involved in stress regulation-specifically, amygdala and hippocampal volumes-in part via mothers' responses to children's distress. We assessed 52 mothers' attachment representations (secure base script knowledge on the Attachment Script Assessment and self-reported attachment avoidance and anxiety on the Experiences in Close Relationships scale) and children's brain structure. Mothers' secure base script knowledge was significantly related to children's smaller left amygdala volume but was unrelated to hippocampal volume; we found no indirect links via maternal responses to children's distress. Exploratory analyses showed associations between mothers' attachment representations and white matter and thalamus volumes. Together, these preliminary results suggest that mothers' attachment representations may be linked to the development of children's neural circuitry related to stress regulation.


Crossover from spherical particle Mie scattering to circular aperture diffraction.
This paper demonstrates the manner in which the Mie results for light scattering by a three-dimensional sphere of arbitrary size and refractive index crosses over to Fraunhofer diffraction by a two-dimensional circular aperture of the same radius in the limit of very large radius. Demonstration is feasible only because the graphical results are plotted in the manner of the Q-space analysis that plots scattered intensity versus the logarithm of the magnitude of the scattering wave vector rather than linear versus the scattering angle.


Reply to "Comment on 'Thomson rings in a disk' ".
We demonstrate that our model [Phys. Rev. E 91, 032312 (2015)PLEEE81539-375510.1103/PhysRevE.91.032312] serves as a useful tool to trace the evolution of equilibrium configurations of one-component charged particles confined in a disk. Our approach reduces significantly the computational effort in minimizing the energy of equilibrium configurations, and it demonstrates a remarkable agreement with the values provided by molecular-dynamics calculations. We show that the Comment misrepresents our paper and fails to provide plausible arguments against the formation hexagonal structure for n≥200 in molecular-dynamics calculations.


Oriented Growth of α-MnO₂ Nanorods Using Natural Extracts from Grape Stems and Apple Peels.
We report on the synthesis of alpha manganese dioxide (α-MnO₂) nanorods using natural extracts from Vitis vinifera grape stems and Malus domestica 'Cortland' apple peels. We used a two-step method to produce highly crystalline α-MnO₂ nanorods: (1) reduction of KMnO₄ in the presence of natural extracts to initiate the nucleation process; and (2) a thermal treatment to enable further solid-state growth of the nuclei. Transmission electron microscopy (TEM) and field emission scanning electron microscopy (FESEM) images provided direct evidence of the morphology of the nanorods and these images were used to propose nucleation and growth mechanisms. We found that the α-MnO₂ nanorods synthesized using natural extracts exhibit structural and magnetic properties similar to those of nanoparticles synthesized via traditional chemical routes. Furthermore, Fourier transform infrared (FTIR) shows that the particle growth of the α-MnO₂ nanorods appears to be controlled by the presence of natural capping agents during the thermal treatment. We also evaluated the catalytic activity of the nanorods in the degradation of aqueous solutions of indigo carmine dye, highlighting the potential use of these materials to clean dye-polluted water.


Urinary incontinence management in geriatric patients.
To review prevalence, causes, types, and appropriate therapy to treat urinary incontinence (UI) in geriatric patients. Selection and extraction from a PubMed/MEDLINE, English-language literature search from 2000 to the present using the search terms urinary incontinence and geriatrics. UI is a prevalent condition in geriatric patients. Unmanaged UI decreases quality of life and increases the risk of perineal skin breakdown, which can lead to painful skin irritation and pressure sores. Identifying the type of UI, and treating or eliminating transient causes as a result of acute conditions or medications, are initial steps in appropriate management. Health professionals can identify medication-related causes by reviewing the patient history, diagnoses, symptoms, and medication regimen. Chronic UI is often caused by physiological changes in the bladder; increasing age also can result in changes in bladder and urethral compliance. Other UI risk factors include impaired function, cognition, mobility, and dexterity as well as neurodegenerative damage that affect the patient's ability to toilet or recognize the need to toilet. Chronic or persistent UI is classified as stress, urge, overflow, functional, or mixed. Treatment options for chronic UI are discussed in detail. Pharmacists can have a positive impact on this condition by recommending appropriate medication changes and pharmacologic and nonpharmacologic treatments.


Pearls & Oy-sters: Whole-Genome Sequencing in Critically Ill Neurologic Patient Leads to Diagnosis With Treatment Implications.
Many adult patients with a history of seizures and global developmental delay do not have an identified etiology for their epilepsy. Rapid whole-genome sequencing (rWGS) can be used to identify a genetic etiology in critically ill patients to provide actionable interventions. In this case, a 27-year-old patient with a history of epilepsy, global developmental delay, and intellectual disability presented with altered mental status and new abnormal movements. The patient acutely declined over the course of 24-48 hours of presentation, including nonconvulsive status epilepticus leading to intubation for airway protection, 2 episodes of ventricular tachycardia requiring synchronized cardioversion, and 1 episode of supraventricular tachycardia. The patient was found to be in metabolic crisis. Metabolic workup and rapid whole-genome sequencing were sent. Patient was treated with 10% dextrose in normal saline and a mitochondrial cocktail. She received treatment with ammonia scavengers and hemodialysis with resolution of metabolic crisis. rWGS found a homozygous pathogenic variant in TANGO2 and a de novo pathogenic variant in KCNQ1, ultimately leading to the creation of a metabolic emergency protocol and implantable cardioverter defibrillator placement. This case highlights the use of rWGS in an acutely ill patient leading to actionable interventions. It also highlights the utility and importance of genetic sequencing in reevaluation of adult neurologic patients.


Mucosal delivery of a pneumococcal vaccine using Lactococcus lactis affords protection against respiratory infection.
Economical and effective vaccines against Streptococcus pneumoniae (pneumococcus) are needed for implementation in poorer countries where the disease burden is highest. Here, we evaluated Lactococcus lactis intracellularly producing the pneumococcal surface protein A (PspA) as a mucosal vaccine in conferring protection against pneumococcal disease. Mice were intranasally (inl) immunized with the lactococcal vaccine. Control groups were also immunized with similar amounts of recombinant PspA administered inl or subcutaneously with alum. PspA-specific antibodies in serum samples and lung lavage fluids were measured before challenge in intraperitoneal sepsis and inl respiratory-infection models of pneumococcal disease. The lactococcal vaccine afforded better protection against respiratory challenge with pneumococcus than did vaccination with purified antigen given inl or by injection with alum. This finding was associated with a shift toward a Th1-mediated immune response characterized by reduced antibody titers to the PspA antigen. In the sepsis model, the lactococcal vaccine afforded resistance to disease on a par with that obtained with the injected vaccine, demonstrating its efficacy against different forms of pneumococcal disease. Given the safety profile of L. lactis, there is considerable potential to develop a pneumococcal vaccine for use in humans and to broaden this approach to combat other major pathogens.


A novel small molecule that kills a subset of MLL-rearranged leukemia cells by inducing mitochondrial dysfunction.
Survival rates for pediatric patients suffering from mixed lineage leukemia (MLL)-rearranged leukemia remain below 50% and more targeted, less toxic therapies are urgently needed. A screening method optimized to discover cytotoxic compounds selective for MLL-rearranged leukemia identified CCI-006 as a novel inhibitor of MLL-rearranged and CALM-AF10 translocated leukemias that share common leukemogenic pathways. CCI-006 inhibited mitochondrial respiration and induced mitochondrial membrane depolarization and apoptosis in a subset (7/11, 64%) of MLL-rearranged leukemia cell lines within a few hours of treatment. The unresponsive MLL-rearranged leukemia cells did not undergo mitochondrial membrane depolarization or apoptosis despite a similar attenuation of mitochondrial respiration by the compound. In comparison to the sensitive cells, the unresponsive MLL-rearranged leukemia cells were characterized by a more glycolytic metabolic phenotype, exemplified by a more pronounced sensitivity to glycolysis inhibitors and elevated HIF1α expression. Silencing of HIF1α expression sensitized an intrinsically unresponsive MLL-rearranged leukemia cell to CCI-006, indicating that this pathway plays a role in determining sensitivity to the compound. In addition, unresponsive MLL-rearranged leukemia cells expressed increased levels of MEIS1, an important leukemogenic MLL target gene that plays a role in regulating metabolic phenotype through HIF1α. MEIS1 expression was also variable in a pediatric MLL-rearranged ALL patient dataset, highlighting the existence of a previously undescribed metabolic variability in MLL-rearranged leukemia that may contribute to the heterogeneity of the disease. This study thus identified a novel small molecule that rapidly kills MLL-rearranged leukemia cells by targeting a metabolic vulnerability in a subset of low HIF1α/low MEIS1-expressing MLL-rearranged leukemia cells.


Low-dose aspirin-induced gastroduodenal mucosal injury in Japanese patients with arteriosclerotic disease.
We aimed to elucidate the risk factors and preventive factors associated with chronic low-dose aspirin (L-ASA)-induced gastroduodenal mucosal injury in Japanese patients with arteriosclerotic disease. This retrospective observational study included 400 L-ASA users who underwent upper gastrointestinal endoscopy. We investigated patients' clinical characteristics, including age, peptic ulcer history, concomitant drugs [i.e. gastric agents, antiplatelet drugs, anticoagulants, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids], abdominal symptoms, endoscopic findings, and interruption of L-ASA before endoscopy. The severity of gastroduodenal mucosal lesions was evaluated using the modified LANZA score (MLS). Of 400 patients, 249 (62%) and 41 (10%) had gastroduodenal mucosal lesions (MLS ≥1) and gastroduodenal ulcers, respectively. Peptic ulcer history, abdominal symptoms, proton pump inhibitor (PPI), histamine type 2-receptor antagonists (H2RA), and the cessation of L-ASA before endoscopy were significantly associated with L-ASA-induced gastroduodenal ulcers; the odds ratio (OR) (confidence interval (CI)) was 5.49 (1.82-16.55), 4.56 (1.93-10.75), 0.12 (0.03-0.42), 0.13 (0.04-0.40) and 0.11 (0.04-0.29), respectively. Moreover, patients having two or more of five factors [i.e. advanced age (≥75), anticoagulants, antiplatelet drugs, NSAIDs and corticosteroids] had a significantly higher prevalence of L-ASA-induced gastroduodenal ulcers [OR (CI): 2.39 (1.002-5.69)]. Peptic ulcer history, abdominal symptoms and the summation of risk factors increased the risk for L-ASA-induced gastroduodenal ulcers. H2RAs and PPIs were effective for the prevention of L-ASA-induced gastroduodenal ulcers. The cessation of L-ASA before endoscopy might lead to the underestimation of L-ASA-induced gastroduodenal injury.


Hyperplasia vs hypertrophy in tissue regeneration after extensive liver resection.
To address to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss. The ability of the liver to regenerate is remarkable on both clinical and biological grounds. Basic mechanisms underlying this process have been intensively investigated. However, it is still debated to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss. We addressed this issue using a genetically tagged system. We were able to follow the fate of single transplanted hepatocytes during the regenerative response elicited by 2/3 partial surgical hepatectomy (PH) in rats. Clusters of transplanted cells were 3D reconstructed and their size distribution was evaluated over time after PH. Liver size and liver DNA content were largely recovered 10 d post-PH, as expected (e.g., total DNA/liver/100 g b.w. was 6.37 ± 0.21 before PH and returned to 6.10 ± 0.36 10 d after PH). Data indicated that about 2/3 of the original residual hepatocytes entered S-phase in response to PH. Analysis of cluster size distribution at 24, 48, 96 h and 10 d after PH revealed that about half of the remnant hepatocytes completed at least 2 cell cycles. Average size of hepatocytes increased at 24 h (248.50 μm2 ± 7.82 μm2, P = 0.0015), but returned to control values throughout the regenerative process (up to 10 d post-PH, 197.9 μm2 ± 6.44 μm2, P = 0.11). A sizeable fraction of the remnant hepatocyte population does not participate actively in tissue mass restoration. Hyperplasia stands as the major mechanism contributing to liver mass restoration after PH, with hypertrophy playing a transient role in the process.


Complementary and alternative medicines in the treatment of dementia: an evidence-based review.
Alternative medicines may have potential beneficial results in treating certain forms of dementia and related symptoms, as well as slowing disease progression. Alternative medicines may ameliorate disturbances in cognition, mood, sleep and activities of daily living. Primary mechanisms of action include modifications in neurotransmitter synthesis, inhibition of neurotransmitter reuptake and enzyme-induced neurotransmitter breakdown, antioxidant and anti-platelet activity, enhanced blood flow and glucose metabolism. Adverse events can include cardiovascular, gastrointestinal, mood, autonomic and dermatologic effects. However, adverse events, when reported represent, a small percentage of treated groups and direct links between adverse events and alternative therapies are tenuous. Many studies of alternative medicines in dementia are inconclusive and characterised by methodological deficiencies such as small sample sizes and inadequate controls. If alternative medicines can be shown to be efficacious using more rigorous experimental designs, both consumers and clinicians could avail themselves of a wider range of pharmacological substances that may offer the advantage of being better tolerated and exhibiting safer therapeutic margins than some allopathic medicines. While a number of complementary interventions have shown both strengths and weaknesses, huperzine A, levacecarnine and EGB 761, based on the overall quality of the studies, identified mechanisms of activity and safety profiles merit further examination in controlled clinical outcome studies.


Activation of Wnt signaling bypasses the requirement for RTK/Ras signaling during C. elegans vulval induction.
During Caenorhabditis elegans vulval development, activation of receptor tyrosine kinase/Ras and Notch signaling pathways causes three vulval precursor cells (VPCs) to adopt induced cell fates. A Wnt signaling pathway also acts in cell fate specification by the VPCs, via regulation of the Hox gene lin-39. We show here that either mutation of pry-1 or expression of an activated BAR-1 beta-catenin protein causes an Overinduced phenotype, in which greater than three VPCs adopt induced cell fates. This indicates that pry-1, which encodes a C. elegans axin homolog, acts as a negative regulator of Wnt signaling in the VPCs. Loss of activity of the APC homolog apr-1 increases the penetrance of this Overinduced phenotype, suggesting that APR-1 may play a negative role in Wnt signaling in this process in C. elegans similar to APC proteins in other systems. The Overinduced phenotype is suppressed by reduction of function of the genes pop-1 TCF and lin-39 Hox. Surprisingly, the Overinduced phenotype caused by hyperactivated Wnt signaling is not dependent on signaling through the Ras pathway. These data suggest that hyperactivation of Wnt signaling is sufficient to cause VPCs to adopt induced fates and that a canonical Wnt pathway may play an important role during C. elegans vulval induction.


Streptococcus suis MsmK: Novel Cell Division Protein Interacting with FtsZ and Maintaining Cell Shape.
Bacteria of different shapes have adopted distinct mechanisms to faithfully coordinate morphogenesis and segregate their chromosomes prior to cell division. Despite recent focuses and advances, the mechanism of cell division in ovococci remains largely unknown. Streptococcus suis, a major zoonotic pathogen that causes problems in human health and in the global swine industry, is an elongated and ellipsoid bacterium that undergoes successive parallel splitting perpendicular to its long axis. Studies on cell cycle processes in this bacterium are limited. Here, we report that MsmK (multiple sugar metabolism protein K), an ATPase that contributes to the transport of multiple carbohydrates, has a novel role as a cell division protein in S. suis MsmK can display ATPase and GTPase activities, interact with FtsZ via the N terminus of MsmK, and promote the bundling of FtsZ protofilaments in a GTP-dependent manner in vitro Deletion of the C-terminal region or the Walker A or B motif affects the affinity between MsmK and FtsZ and decreases the ability of MsmK to promote FtsZ protofilament bundling. MsmK can form a complex with FtsZ in vivo, and its absence is not lethal but results in long chains and short, occasionally anuclear daughter cells. Superresolution microscopy revealed that the lack of MsmK in cells leads to normal septal peptidoglycan walls in mother cells but disturbed cell elongation and peripheral peptidoglycan synthesis. In summary, MsmK is a novel cell division protein that maintains cell shape and is involved in the synthesis of the peripheral cell wall.IMPORTANCE Bacterial cell division is a highly ordered process regulated in time and space and is a potential target for the development of antimicrobial drugs. Bacteria of distinct shapes depend on different cell division mechanisms, but the mechanisms used by ovococci remain largely unknown. Here, we focused on the zoonotic pathogen Streptococcus suis and identified a novel cell division protein named MsmK, which acts as an ATPase of the ATP-binding cassette-type carbohydrate transport system. MsmK has GTPase and ATPase activities. In vitro protein assays showed that MsmK interacts with FtsZ and promotes FtsZ protofilament bundling that relies on GTP. Superresolution microscopy revealed that MsmK maintains cell shape and is involved in peripheral peptidoglycan synthesis. Knowledge of the multiple functions of MsmK may broaden our understanding of known cell division processes. Further studies in this area will elucidate how bacteria can faithfully and continually multiply in a constantly changing environment.


Should I stay or should I go: biogeographic and evolutionary history of a polyploid complex (Chrysanthemum indicum complex) in response to Pleistocene climate change in China.
Quaternary climatic oscillations greatly influenced the distribution and pattern of biodiversity in the Northern Hemisphere. Here we examine how such oscillations in South East Asia may have affected the demographic and evolutionary history of a polyploid plant complex associated with semi-dry habitats. We analyzed plastid and nuclear ribosomal DNA (rDNA) internal transcribed spacer (ITS) sequence variation within the Chrysanthemum indicum complex (Asteraceae), which comprises diploid and polyploid plants distributed throughout China. In total, 368 individuals from 47 populations across the geographical range of the complex were analyzed. We show that the relatively widespread tetraploid form of C. indicum expanded its range southward in the Pleistocene, possibly during the most recent or previous glacial period when conditions became drier and forests retreated in southern China. In marked contrast, diploid and other polyploid members of the complex failed to expand their ranges at these times or have since undergone range contractions in contrast to tetraploid C. indicum. We conclude that hybridization and gene flow between taxa occurred frequently during the evolutionary history of the complex, causing considerable sharing of chlorotypes and ITS types. Nevertheless, taxa within ploidy levels could be largely distinguished according to chlorotype and/or ITS type.


New methods in the diagnosis of cancer and gene therapy of cancer based on nanoparticles.
Cancer is one of the leading cause of death in the world with the prevalence of >10 million mortalities annually. Current cancer treatments include surgical intervention, radiation, and taking chemotherapeutic drugs, which often kill the healthy cells and result in toxicity in patients. Therefore, researchers are looking for ways to be able to eliminate just cancerous cells. Intra-tumor heterogeneity of cancerous cells is the main obstacle on the way of an effective cancer treatment. However, better comprehension of molecular basis of tumor and the advent of new diagnostic technologies can help to improve the treatment of various cancers. Therefore, study of epigenetic changes, gene expression of cancerous cells and employing methods that enable us to correct or minimize these changes is critically important. In this paper, we will review the recent advanced strategies being used in the field of cancer research.


Standardized Reporter Systems for Purification and Imaging of Human Pluripotent Stem Cell-derived Motor Neurons and Other Cholinergic Cells.
Reliable and consistent pluripotent stem cell reporter systems for efficient purification and visualization of motor neurons are essential reagents for the study of normal motor neuron biology and for effective disease modeling. To overcome the inherent noisiness of transgene-based reporters, we developed a new series of human induced pluripotent stem cell lines by knocking in tdTomato, Cre, or CreERT2 recombinase into the HB9 (MNX1) or VACHT (SLC18A3) genomic loci. The new lines were validated by directed differentiation into spinal motor neurons and immunostaining for motor neuron markers HB9 and ISL1. To facilitate efficient purification of spinal motor neurons, we further engineered the VACHT-Cre cell line with a validated, conditional CD14-GFP construct that allows for both fluorescence-based identification of motor neurons, as well as magnetic-activated cell sorting (MACS) to isolate differentiated motor neurons at scale. The targeting strategies developed here offer a standardized platform for reproducible comparison of motor neurons across independently derived pluripotent cell lines.


Pustules on the back possibly triggering toxic-shock syndrome.
We herein describe an irregular case of toxic-shock syndrome (TSS). A previously healthy 28-year-old Japanese man developed a sudden-onset high fever. The patient was suffering from conjunctival hyperaemia, gastrointestinal symptoms such as vomiting and diarrhoea, and systemically diffused macular erythroderma. Further physical examination detected pustules on his back, which self-destructed over time. Laboratory revealed multiple organ failures. Subsequently, scalded skin on the face and desquamation in the limb extremities emerged by day 10, leading to the diagnosis of TSS, despite his stable circulatory dynamics through the course. Learning points for clinicians include that they should recall TSS as a possible disease concurrently causing high fever, systemic rash and multiple organ dysfunctions, even without being in a state of shock. The characteristic desquamations emerged in the limb extremities after hospitalisation were of help in diagnosing TSS.


Midgut transcriptomal response of the rice leaffolder, Cnaphalocrocis medinalis (Guenée) to Cry1C toxin.
Cnaphalocrocis medinalis (Guenée) is one of the important insect pests in rice field. Bt agents were recommended in the C. medinalis control and Bt rice is bred as a tactic to control this insect. However, the tolerance or resistance of insect to Bt protein is a main threat to the application of Bt protein. In order to investigate the response of C. medinalis transcriptome in defending a Cry1C toxin, high-through RNA-sequencing was carried in the C. medinalis larvae treated with and without Cry1C toxin. A total of 35,586 high-quality unigenes was annotated in the transcriptome of C. medinalis midgut. The comparative analysis identified 6,966 differently expressed unigenes (DEGs) between the two treatments. GO analysis showed that these genes involved in proteolysis and extracellular region. Among these DEGs, carboxylesterase, glutathione S-transferase and P450 were differently expressed in the treated C. medinalis midgut. Furthermore, trypsin, chymotrypsin, and carboxypeptidase were identified in DEGs, and most of them up-regulated. In addition, thirteen ABC transporters were downregulated and three upregulated in Cry1C-treated C. medinalis midgut. Based on the pathway analysis, antigen processing and presentation pathway, and chronic myeloid leukemia pathway were significant in C. medinalis treated with Cry1C toxin. These results indicated that serine protease, detoxification enzymes and ABC transporter, antigen processing and presentation pathway, and chronic myeloid leukemia pathway may involved in the response of C. medinalis to Cry1C toxin. This study provides a transcriptomal foundation for the identification and functional characterization of genes involved in the toxicity of Bt Cry protein against C. medinalis, and provides potential clues to the studies on the tolerance or resistance of an agriculturally important insect pest C. medinalis to Cry1C toxin.


Using fluorescence and circular dichroism (CD) spectroscopy to investigate the interaction between di-n-butyl phthalate and bovine serum albumin.
The interaction between di-n-butyl phthalate (DBP) and bovine serum albumin (BSA) in physiological Tris-HCl buffer at pH 7.4 was investigated by fluorescence quenching technique. By analyzing the fluorescence spectrum and intensity, it was observed that the DBP had a strong ability to quench the intrinsic fluorescence of BSA through a static quenching procedure. The binding constants K and the number of binding sites n of DBP with BSA were calculated to be 0.11 × 102 L·mol-1 and 0.52 at 298 K, respectively. The thermodynamic parameters of enthalpy change (ΔH) and entropy change (ΔS) were also calculated to be positive showing that hydrophobic forces might play a major role in the binding of DBP to BSA. The binding process was spontaneous in which Gibbs free energy change (ΔG) was negative. The distance (r) between the donor (BSA) and acceptor (DBP) was calculated to be 2.02 nm based on Forster's non-radiative energy transfer theory, which indicated that the energy transfer from BSA to DBP occurs with a high possibility. The synchronous fluorescence, three-dimensional fluorescence, and circular dichroism (CD) spectra showed that the binding of di-n-butyl phthalate to BSA induced conformational changes in BSA. The interaction between DBP and BSA can help researchers better understand the nature of poisons and serve people in the right way with first aid and detoxification.


The survival of costal cartilage graft in laryngotracheal reconstruction.
Acquired subglottic stenosis in children is a difficult problem. One of the successful procedures used to correct this condition is an autogenous costal cartilage graft to the subglottis and upper trachea. The fate of the cartilage graft is not known, despite the good results of the procedure. Prompted by recovery of viable cartilage graft from two patients previously operated upon by this procedure, we performed autogenous costal cartilage grafting to the subglottic area of fifty young New Zealand rabbits, with inspection of these grafts at 2- and 4-month postoperative intervals. The purpose of this study is to prove the survival of autogenous costal cartilage grafts in the subglottic area. Gross and histologic examination 2 and 4 months postoperatively showed viable cartilage as well as lining of the graft with respiratory epithelium in the majority of cases.


Comparative diagnostic accuracy of 18F-FDG PET/CT for breast cancer recurrence.
In the last decades, in addition to conventional imaging techniques and magnetic resonance imaging (MRI), 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) has been shown to be relevant in the detection and management of breast cancer recurrence in doubtful cases in selected groups of patients. While there are no conclusive data indicating that imaging tests, including FDG PET/CT, produce a survival benefit in asymptomatic patients, FDG PET/CT can be useful for identifying the site of relapse when traditional imaging methods are equivocal or conflicting and for identifying or confirming isolated loco-regional relapse or isolated metastatic lesions. The present narrative review deals with the potential role of FDG PET in these clinical settings by comparing its accuracy and impact with conventional imaging modalities such as CT, ultrasound, bone scan, 18F-sodium fluoride PET/CT (18F-NaF PET/CT) as well as MRI. Patient-focused perspectives in terms of patients' satisfaction and acceptability are also discussed.


Risk factors predicting the occurrence of metachronous ovarian metastasis of gastric cancer.
Ovarian metastasis following radical gastrectomy, also known as metachronous ovarian metastasis (MOM), pose a significant threat to the long-term survival of female gastric cancer (GC) patients. However, a mechanism to identify and characterize operated patients at high risk of developing MOM remains unknown. This retrospective study aimed to identify risk factors for the occurrence of MOM based on the profiling of clinicopathological parameters and expression of sex hormone receptors (SHR) of operated GC patients with and without ovarian relapse. The clinicopathological data of 1,055 female GC patients from two medical centers who underwent surgery between January 2011 and December 2015 were reviewed. A total of 378 patients with and without the occurrence of MOM met the eligibility criteria, including the availability of medical records, adequacy of lymph node dissection, completeness of clinicopathological data, sufficient follow-up time, and no administration of neoadjuvant chemotherapy were selected for further analysis. Expressions of estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and progesterone receptor (PR) were detected by immunohistochemical staining on the surgical specimens of patients, and retrospective statistical analyses identified independent risk factors for the occurrence of MOM. A risk prediction model in the format of a polygenic hazard score (PHS) for the occurrence of MOM was established by introducing and modifying the previously validated polygenic risk score (PRS)/PHS. A Cox regression-based multivariate analysis identified premenopausal with an HR of 3.15 (95% CI, 1.66-5.98), more advanced pathological T stage with an HR of 3.79 (95% CI, 2.14-6.69), more advanced pathological N stage with an HR of 1.85 (95% CI, 1.35-2.54), and negative expression of ERβ with an HR of 0.33 (95% CI, 0.15-0.7) as independent risk factors for the occurrence of MOM (P<0.01). Accordingly, a PHS for the occurrence of MOM was established, with 1-, 2-, and 3-year ovarian relapse rates for the high-risk group estimated at 17.8%, 33.7%, and 46.2%, respectively. Premenopausal status, depth of tumor invasion, number of positive lymph nodes, and negative expression of ERβ were independent factors for the occurrence of MOM. More frequent follow-up examinations are recommended to provide timely diagnosis and medical intervention.


Carcinogenic action of quinoxaline 1,4-dioxide in rats.
Quinoxaline 1,4-dioxide was fed to 400 rats at levels of 10 mg or 1 mg/kg body weight for 18 months. It produced a high incidence of nasal and liver tumors only in the group fed 10 mg/kg. Of diverse histologies, the nasal tumors included anaplastic carcinomas, adenocarcinomas, squamous cell carcinomas, neuroepitheliomas, basal cell carcinomas, and a single fibrosarcoma. The nasal epithelium not involved in the neoplastic process showed dysplasia and hyperplasia.


Conditioned hyperkinesia induced by cocaine in mice is dose-dependent but not correlated with the unconditioned response or the contextually-sensitized response.
The aims of the study were to test whether drug dose is positively related to the magnitude of the conditioned response following sensitization to the behavioural effects of cocaine and to investigate the relationship between the conditioned response and cocaine-induced sensitization. Male mice (C57BL/6J) were first injected over seven successive days with either saline or cocaine at 2.5, 5, 10 or 20 mg/kg s.c., in the testing room. On the test day, 24 h after the last injection, mice from all conditions were challenged with saline in the testing room to test for conditioned cocaine effects. Mice were video-recorded and various behaviours were later scored using a time-sampling technique. Cocaine-elicited orofacial stereotypy was significantly sensitized at the two highest doses and dose-dependently conditioned at the three highest doses. Cocaine-increased locomotion was sensitized at the three highest doses and significantly conditioned at 10 and 20mg/kg. Cocaine-increased sniffing did not change over pretreatment at any dose, and was conditioned only at 10 mg/kg. Cocaine-decreased immobility also did not change over pretreatment at any dose, but was conditioned at 10 and 20mg/kg. Concomitantly, rearing was reduced by cocaine at 10 and 20mg/kg, without sensitization being induced, and it was reduced under saline challenge after 5 mg/kg cocaine, while cocaine-decreased grooming was sensitized at the three highest doses and conditioned at 10 and 20 mg/kg cocaine. There was a positive relation between the size of the conditioned response for orofacial stereotypy and the magnitude of the unconditioned stimulus (the doses), a result conforming to the Pavlovian account of the placebo effect. This could also be concluded from considering the behaviour patterns as components of a unique placebo effect (hyperkinetic syndrome), since orofacial stereotypy, very apparent at 20 mg/kg cocaine, interfered at that dose with the full-blown expression of locomotion and sniffing, both yielding (approximately) inverted U-shaped dose-effect curves. However, no correlation was found between the magnitude of the conditioned response and the amplitude of sensitization (the difference between the initial unconditioned non-sensitized response and the last unconditioned sensitized response), a finding which indicates that conditioned responding does not participate in the generation of the sensitized effects, contrary to the 'excitatory conditioning model of contextual sensitization'.


Next-generation sequencing and genetic diagnosis of Charcot-Marie-Tooth disease.
Over 70 different Charcot-Marie-Tooth disease (CMT)-associated genes have now been discovered and their number is growing. Conventional genetic testing for all CMT genes is cumbersome, expensive, and impractical in an individual patient. Next-generation sequencing (NGS) technology allows cost-effective sequencing of large scale DNA, even entire exome (coding sequences) or whole genome and thus, NGS platform can be employed to effectively target a large number or all CMT-related genes for accurate diagnosis. This overview discusses how NGS can be strategically used for genetic diagnosis in patients with CMT or unexplained neuropathy. A comment is made to combine simple clinical and electrophysiological algorithm to assign patients to major CMT subtypes and then employ NGS to screen for all known mutations in the subtype-specific CMT gene panel.


Quantitative Temperature Dependence of the Microscopic Hydration Structures Investigated by Ultraviolet Photodissociation Spectroscopy of Hydrated Phenol Cations.
To discuss the temperature effect on microscopic hydration structures in clusters, relative populations of the isomers having different hydration structures at well-defined temperatures are quite important. In the present study, we measured ultraviolet photodissociation spectra of the temperature-controlled hydrated phenol cation [PhOH(H2O)5]+ trapped in the 22-pole ion trap. Two isomers having a distinct hydration motif with each other are identified in the spectra, and a clear change in the relative populations is observed in the temperature range from 30 to 150 K. This behavior is quantitatively interpreted by statistical mechanical estimation based on density functional theory calculations. A ring with tail-type hydration motif is dominant in cold conditions, whereas a chain-like motif is dominant in hot conditions. The present study provides very quantitative information about the temperature effect on the microscopic hydration structures.


Women in neuroscience (WIN): the first twenty years.
Women in Neuroscience (WIN) is an international organization whose major goal is to promote the professional advancement of women neuroscientists. To this end, WIN facilitates contacts and communication among women working in neuroscience, and organizes appropriate activities at the annual Society for Neuroscience (SfN) meeting. WIN was created in 1980, when despite major changes and advances in 'equal opportunities', women were still not achieving a proportionate level of success in the subdiscipline of neurosciences. In 1980, women made up 40 to 50% of entering classes in medical schools or graduate programs, but often comprised only 5 to 15% of leadership in respective organizations. Although there had been women elected to serve as SfN presidents, council, and committee members, women were under-represented in other positions of the Society, such as symposium and session chairs. There was an even lesser degree of representation in leadership positions at universities and medical schools in terms of full professorships, chairs, and program directors, as well as on editorial boards, advisory boards, and councils. Over the years, WIN has worked with success toward increasing the participation of women in neuroscience.


Online sequential-injection chromatography with stepwise gradient elution: a tool for studying the simultaneous adsorption of herbicides on soil and soil components.
The adsorption of triazine herbicides simazine (SIM), atrazine (ATR), and propazine (PRO) as well as the metabolites deisopropylatrazine (DIA), deethylatrazine (DEA), and 2-hydroxyatrazine (HAT) on soil, humic acid, and soil modified with humic acidic was studied by sequential-injection chromatography with UV detection at 223 nm. An online monitoring system was assembled, which was composed of a tangential filter and a peristaltic pump for the circulation of the soil (25 g L(-1)) or humic acid (2.5 g L(-1)) suspensions. A stepwise gradient elution separated the compounds using three mobile phases whose compositions were 28, 40, and 50% (v v(-1)) methanol in 1.25 mmol L(-1) ammonium acetate buffer, pH 4.7. The sampling throughput was about six analyses per hour; the linear dynamic range was between 100 and 1000 μg L(-1) for all of the studied compounds. The detection limits varied from 9 μg L(-1) for ATR to 36 μg L(-1) for DEA. At contact times <2 h, humic acid was the material with a higher adsorptive capacity (from 1470 ± 43 μg g(-1) for DIA to 2380 ± 51 μg g(-1) for PRO). In soil, HAT exhibited the highest adsorption (23.8 ± 0.2 μg g(-1)). The presence of humic acid in the soil increased the adsorption of ATR (14 ± 1 to 23 ± 2 μg g(-1)) and PRO (21.5 ± 0.5 to 24.0 ± 0.2 μg g(-1)), decreased the adsorption of HAT (23.8 ± 0.2 to 18 ± 2 μg g(-1)), and did not affect DIA and DEA. The adsorption of SIM was negligible in all of the sorbents studied. Simazine is the herbicide with the greatest potential for leaching to water bodies followed by DEA and DIA.


The receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in the mouse hepatoma cell line Hepa 1c1c7. A comparison with the glucocorticoid receptor and the mouse and rat hepatic dioxin receptors.
The molecular properties of the receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in the mouse hepatoma cell line Hepa 1c1c7 were investigated. The receptor was found to represent a highly asymmetrical molecule with a sedimentation coefficient, s20,w, of approximately 8 S, a Stokes radius of 7-8 nm, and a calculated Mr approximately equal to 260,000-300,000. In comparison, the Hepa 1c1c7 glucocorticoid receptor in analogy to the glucocorticoid receptor in general as well as the C57BL/6 mouse and rat hepatic dioxin receptors are molecules with an s20,w value of 4-5 S, a Stokes radius of approximately 6 nm, and a calculated Mr approximately equal to 100,000. In the presence of 20 mM sodium molybdate, a large Mr approximately equal to 270,000-310,000 form of the Hepa 1c1c7 glucocorticoid receptor is stabilized which is hydrodynamically indistinguishable from the Mr approximately equal to 260,000-300,000 Hepa 1c1c7 dioxin receptor. Sodium molybdate does not have any effect on the molecular properties of the Hepa 1c1c7 dioxin receptor. In conclusion, the large form of dioxin receptor present in Hepa 1c1c7 mouse hepatoma cells in the absence of sodium molybdate is strikingly similar to molybdate-stabilized steroid hormone receptors as well as the molybdate-stabilized form of the dioxin receptor previously demonstrated in rat hepatic cytosol. Therefore, the Hepa 1c1c7 dioxin receptor might offer an interesting model for studies on the structure and function of Mr approximately equal to 300,000 forms of soluble receptors.


Severe Dermatophytosis and Acquired or Innate Immunodeficiency: A Review.
Dermatophytes are keratinophilic fungi responsible for benign and common forms of infection worldwide. However, they can lead to rare and severe diseases in immunocompromised patients. Severe forms include extensive and/or invasive dermatophytosis, i.e., deep dermatophytosis and Majocchi's granuloma. They are reported in immunocompromised hosts with primary (autosomal recessive CARD9 deficiency) or acquired (solid organ transplantation, autoimmune diseases requiring immunosuppressive treatments, HIV infection) immunodeficiencies. The clinical manifestations of the infection are not specific. Lymph node and organ involvement may also occur. Diagnosis requires both mycological and histological findings. There is no consensus on treatment. Systemic antifungal agents such as terbinafine and azoles (itraconazole or posaconazole) are effective. However, long-term outcome and treatment management depend on the site and extent of the infection and the nature of the underlying immunodeficiency.


Detection of methanotrophs with highly divergent pmoA genes from Arctic soils.
Tundra soil samples from the Canadian Arctic community, Kuujjuaq, were analyzed for the presence of the soluble (sMMO) and particulate (pMMO) methane monooxygenase genes. Total genomic DNA extracted from these soils was used as template for PCR using sMMO- and pMMO-specific primers, mmoX1-mmoX2 and A189-A682, respectively. pMMO and sMMO genes were detected in the Kuujjuaq soil samples. Isolation of sMMO-possessing methanotrophic microorganisms from the three soils, as determined by the colony naphthalene oxidation assay, was carried out using direct plating (5 degrees C) and methane enrichment studies (5 degrees C and 25 degrees C). Direct plating did not yield sMMO-possessing methanotrophic bacteria, whereas methane enrichments yielded isolates possessing and expressing sMMO activity. Analysis of derived amino acid sequences of pmoA genes and partial 16S rRNA genes obtained by PCR, using DNA isolated directly from this environment and from isolates, revealed the presence of highly divergent PmoA/AmoA sequences and 16S rRNA sequences that cluster closely with but are distinct from the genes from the genera Methylosinus and Methylocystis.


Positive regulation of apoptosis signal-regulating kinase 1 by dual-specificity phosphatase 13A.
Apoptosis signal-regulating kinase 1 (ASK1), a member of the MAP kinase kinase kinase, is activated by several death stimuli and is tightly regulated by several mechanisms such as interactions with regulatory proteins and post-translational modifications. Here, we report that dual-specificity phosphatase 13A (DUSP13A) functions as a novel regulator of ASK1. DUSP13A interacts with the N-terminal domain of ASK1 and induces ASK1-mediated apoptosis through the activation of caspase-3. DUSP13A enhances ASK1 kinase activity and thus its downstream factors. Small interfering RNA (siRNA) analyses show that knock-down of DUSP13A in human neuroblastoma SK-N-SH cells reduces ASK1 kinase activity. The phosphatase activity of DUSP13A is not required for the regulation of ASK1. This regulatory action of DSUP13 on ASK1 activity involves competition with Akt1, a negative regulator of ASK1, for binding to ASK1. Taken together, this study provides novel insights into the role of DUSP13A in the precise regulation of ASK1.


Duodenal obstruction secondary to congenital web in an adult.
Congenital duodenal web, although rare, may be more common than presently appreciated. The possibility of this condition should be considered in the differential diagnosis of duodenal obstruction in the adult. It should be treated surgically either by duodenotomy with excision of the web or by duodenojejunostomy. The results are excellent, as illustrated by the authors in their report of a 58-year-old man with this condition, who was treated by duodenojejunostomy.


Emerging concepts for the treatment of hematological malignancies with therapeutic monoclonal antibodies.
The development of therapeutic monoclonal antibodies (mAbs) has revolutionized the treatment of cancer along the last ten years. The best examples of their therapeutic efficacies have been obtained with rituximab for the treatment of CD20+ B-cell Non-Hodgkin Lymphoma (B-NHL), and several others antibodies with optimized bioactivities are now being developed for the treatment of various malignant hemopathies. We review here the main drugs developed in this field, and present some emerging concepts able to improve the bioactivities of the next generation of therapeutic mAbs.


Immunochemical Cross-Reactivity of β-Glucan in the Medicinal Plant, Sasa veitchii (Japanese Folk Medicine Kumazasa), and Medicinal Mushrooms.
Fungal β-glucan is a representative pathogen-associated molecular pattern from mushroom, yeast, and fungi and stimulates innate as well as acquired immune systems. This β-glucan is widely applied in functional food to enhance immunity. Humans and animals generally become sensitized to this β-glucan and gradually produce specific antibodies to β-glucans. The extracts of plants have been used as folk medicine and are reported to possess various biological activities that are beneficial for human health, such as antitumor, antiallergic, and anti-inflammatory activities. In the present study, the immunochemical cross-reactivity of Sasa extract and fungal β-glucan was analyzed. We found that the anti-β-glucan antibody in human sera strongly cross-reacted with the Sasa extract. This result strongly suggested that plant extracts modulate the immunostimulating effects of medicinal mushrooms. The cooperative effects of plants and mushrooms may be an important issue for functional foods.


Adrenomedullary and beta-adrenergic participation in enhanced sympathetic pressor responses of spontaneously hypertensive rats.
The beta-adrenergic and adrenomedullary components of pressor responses to sympathetic nerve stimulation were studied in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). The effects of electrical stimulation of the entire spinal cord of pithed rats pretreated with tubocurarine and atropine were studied on systolic blood pressure, heart rate and plasma cyclic AMP levels. The heart rate increase upon low frequency stimulation (1 Hz) and the blood pressure elevation upon stimulation at higher frequencies (3 and 5 Hz) were higher in SHR than in WKY whereas the increase in circulating cyclic AMP level was not different in the two strains. Pretreatment with propranolol (2.5 mg X kg-1) further enhanced the pressor responses in SHR but not in WKY, although it inhibited the heart rate acceleration and decreased the circulating level of cyclic AMP similarly in the two strains. After acute adrenalectomy, the elevations of blood pressure and circulating cyclic AMP levels were reduced to an identical level in SHR and WKY. These results show that the marked enhancement of the pressor response observed in SHR upon stimulation of the entire sympathetic outflow is mostly of adrenomedullary origin and includes a hypotensive component due to beta-adrenoceptor stimulation which is not present in WKY.


Designing stem-cell-based dopamine cell replacement trials for Parkinson's disease.
Clinical studies of Parkinson's disease (PD) using a dopamine cell replacment strategy have been tried for more than 30 years. The outcomes following transplantation of human fetal ventral mesencephalic tissue (hfVM) have been variable, with some patients coming off their anti-PD treatment for many years and others not responding and/or developing significant side effects, including graft-induced dyskinesia. This led to a re-appraisal of the best way to do such trials, which resulted in a new European-Union-funded allograft trial with fetal dopamine cells across several centers in Europe. This new trial, TRANSEURO ( NCT01898390 ), is an open-label study in which some individuals in a large observational cohort of patients with mild PD who were undergoing identical assessments were randomly selected to receive transplants of hfVM. The TRANSEURO trial is currently ongoing as researchers have completed both recruitment into a large multicenter observational study of younger onset early-stage PD and transplantation of hfVM in 11 patients. While completion of TRANSEURO is not expected until 2021, we feel that sharing the rationale for the design of TRANSEURO, along with the lessons we have learned along the way, can help inform researchers and facilitate planning of transplants of dopamine-producing cells derived from human pluripotent stem cells for future clinical trials.


Demonstration of calcium-dependent proteases (calpains) and thyroglobulin proteolysis in hog thyroid cytosol.
Ca2+-dependent neutral proteases in hog thyroid cytosol were found to digest thyroglobulin. The protease activity was divided into two peaks by DEAE-cellulose column chromatography. Peak I was eluted at 0.2 M NaCl and required only a micromolar range of Ca2+ for its 50% activation, while peak II, which was eluted at about 0.4 M NaCl, displayed little activity until the Ca2+ concentration was increased at more than 10(-4) M. Among various inhibitors used, thiol protease inhibitors (leupeptin, E-64 and monoiodoacetic acid) were the most effective, whereas a calmodulin antagonist (trifluoperazine) and serine protease inhibitors (phenylmethyl-sulfony-fluoride and pepstatin A) were not effective, indicating that these Ca2+-dependent proteases corresponded to calpains 1 and 2. Among the substrates tested, casein was the best and thyroglobulin was also a good for calpain 2. By using immunoblotting procedure with anti-thyroglobulin antibody, it has been found that calpain 2 degrades thyroglobulin to yield 67 K and 46 K thyroglobulin and further that it also degrades 40 K thyroglobulin.


General anaesthesia for lobectomy in an 8-year-old child with Kartagener's syndrome.
Kartagener's syndrome (KGS) is an autosomal recessive disorder characterized by the clinical triad of bronchiectasis, sinusitis and dextrocardia (situs inversus). Reports of general anaesthesia in a child with KGS are rare in medical literature. We describe the case of a young boy who underwent lobectomy under general anaesthesia using a single lumen tube. Anaesthetic implications of this syndrome are mentioned. Key points in the management of anaesthesia in KGS are discussed.


Pasteurella multocida-associated sinusitis in khaki Campbell ducks (Anas platyrhynchos).
Pasteurella multocida group B, serotype 3, was isolated from sinusitis-affected khaki Campbell ducks. To study the role of P. multocida in sinusitis, commercial khaki Campbell ducks were experimentally infected with P. multocida alone or combined with Escherichia coli. In Expt. 1, experimental ducks were infected with P. multocida intranasally or ocularly. A comparison was done by intranasal inoculation with pooled nasal discharge from the affected ducks or phosphate-buffered saline. The ducks intranasally inoculated with the nasal discharge or P. multocida showed sinusitis. In Expt. 2, E. coli alone or a combination of P. multocida and E. coli was intranasally inoculated into experimental ducks. The ducks intranasally inoculated with the combination of P. multocida and E. coli had sinusitis, the same as found in the field but less severe than that of the field cases. Pasteurella multocida was already present in litter/floor of duck farms. We concluded that P. multocida played a role in induction of sinusitis. However, the sinusitis in ducks may be initiated by poor management, especially in the brooding period of ducks.


Aza- and oxadithiolates are probable proton relays in functional models for the [FeFe]-hydrogenases.
The dithiolate cofactor for the [FeFe]-hydrogenase models, Fe(2)(xdt)(CO)(2)(dppv)(2) (where xdt = 1,3-propanedithiolate (pdt), azadithiolate (adt), (SCH(2))(2)NH, and oxadithiolate (odt), (SCH(2))(2)O; dppv = cis-1,2-bis(diphenylphosphino)ethylene) have been probed for their functionality as proton relays enabling formation and deprotonation of terminal hydrides. Compared to the propanedithiolate derivative, the azadithiolate and oxaditiholate show enhanced rates of proton transfer between solution and the terminal site on one Fe center. The results are consistent with the heteroatom of the dithiolate serving a gating role for both protonation and deprotonation. The pK(a) of the transiently formed ammonium (pK(CD(2))(Cl(2)) 5.7-8.2) or oxonium (pK(CD(2))(Cl(2)) -4.7-1.6) regulates the proton transfer. As a consequence, only the azadithiolate is capable of yielding the terminal hydride from weak acids. The aza- and oxadithiolates manifested the advantages of proton relays: the odt derivative proved to be a faster catalyst for hydrogen evolution than the pdt derivative as indicated from cyclic voltammetry plots of i(c)/i(p) vs [H(+)]. The adt derivative was capable of proton reduction from the weak acid [HPMe(2)Ph]BF(4) (pK(CD(2))(Cl(2)) = 5.7). The proton relay function does not apply to the isomeric bridged-hydrides [Fe(2)(xdt)(mu-H)(CO)(2)(dppv)(2)](+), where the hydride is too distant and too basic to interact to be affected by the heteroatomic relay site. None of these mu-H species can be deprotonated.


Analysis of the insecticide resistance mechanism in Anopheles culicifacies sensu lato from a malaria-endemic state in India.
Understanding the dynamics and mechanisms of insecticide resistance in malaria vectors is crucial for vector control activities. The present study investigates the level of insecticide resistance in Anopheles culicifacies and explores the role of two main mechanisms in conferring resistance target site insensitivity and metabolic resistance. A. culicifacies mosquitoes were collected and the voltage-gated sodium channel (VGSC) gene was amplified and sequenced to analyse the knockdown resistance (kdr) mutations. Further, a non-experimental homology model was generated to investigate the effect of kdr mutations on the conformation of protein. Metabolic resistance was determined using bioassay-based resistant and susceptible mosquitoes and the expression levels of the genes CYP6Z1 and GSTe2 were compared between the two groups. Sequence analysis of the VGSC gene revealed the presence of L1014F (n=48 [17%]), L1014S and V1010L (n=5 [1.7%]) mutations in the study area. In gene expression studies, a significant upregulation of CYP6Z1 in deltamethrin-resistant (fold change 243.62; p=0.02) mosquitoes and that of GSTe2 in dichlorodiphenyltrichloroethane (fold change 403.45; p=0.01) and alpha-cypemethrin resistant (fold change 217.51; p=0.0005) mosquitoes was observed. The study revealed that expression of the genes (CYP6Z1 and GSTe2) conferring metabolic resistance play a key role in insecticide resistance in A. culicifacies populations in central India. However, mutations L101F, L10104S and V10101L also have a role to some extent in spreading resistance. GeneBank accession numbers: MW559058, MW559059 and MW559060 Cover Image: Workflow of Chimera-Modeller interface. In the top window of Chimera's multi-align viewer the sequence alignment of VGSC proteins of human (pdb id_6AGF), cockroach (pdb id 5XOM) and A. culicifacies (ACT176122.1) is shown. The dialog box in the middle is of the comparative modelling tool of Modeller. The A. culicifacies sequence is designated as the target while human and cockroach sequences are templates. Upon selection of the template sequences in the dialog box, the structures of the respective proteins are displayed in the Chimera window. As the run is completed, the results are displayed in the form of a list of models with their scores in a table.


A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus.
The recent Ebola virus (EBOV) epidemic highlighted the need for effective vaccines and therapeutics to limit and prevent outbreaks. Host antibodies against EBOV are critical for controlling disease, and recombinant monoclonal antibodies (mAbs) can protect from infection. However, antibodies mediate an array of antiviral functions including neutralization as well as engagement of Fc-domain receptors on immune cells, resulting in phagocytosis or NK cell-mediated killing of infected cells. Thus, to understand the antibody features mediating EBOV protection, we examined specific Fc features associated with protection using a library of EBOV-specific mAbs. Neutralization was strongly associated with therapeutic protection against EBOV. However, several neutralizing mAbs failed to protect, while several non-neutralizing or weakly neutralizing mAbs could protect. Antibody-mediated effector functions, including phagocytosis and NK cell activation, were associated with protection, particularly for antibodies with moderate neutralizing activity. This framework identifies functional correlates that can inform therapeutic and vaccine design strategies against EBOV and other pathogens.


The female gametophyte and the endosperm control cell proliferation and differentiation of the seed coat in Arabidopsis.
Double fertilization of the female gametophyte produces the endosperm and the embryo enclosed in the maternal seed coat. Proper seed communication necessitates exchanges of signals between the zygotic and maternal components of the seed. However, the nature of these interactions remains largely unknown. We show that double fertilization of the Arabidopsis thaliana female gametophyte rapidly triggers sustained cell proliferation in the seed coat. Cell proliferation and differentiation of the seed coat occur in autonomous seeds produced in the absence of fertilization of the multicopy suppressor of ira1 (msi1) mutant. As msi1 autonomous seeds mostly contain autonomous endosperm, our results indicate that the developing endosperm is sufficient to enhance cell proliferation and differentiation in the seed coat. We analyze the effect of autonomous proliferation in the retinoblastoma-related1 (rbr1) female gametophyte on seed coat development. In contrast with msi1, supernumerary nuclei in rbr1 female gametophytes originate mainly from the endosperm precursor lineage but do not express an endosperm fate marker. In addition, defects of the rbr1 female gametophyte also reduce cell proliferation in the ovule integuments before fertilization and prevent further differentiation of the seed coat. Our data suggest that coordinated development of the seed components relies on interactions before fertilization between the female gametophyte and the surrounding maternal ovule integuments and after fertilization between the endosperm and the seed coat.


Effects of metallic contacts on electron transport through graphene.
We report on a first-principles study of the conductance through graphene suspended between Al contacts as a function of junction length, width, and orientation. The charge transfer at the leads and into the freestanding section gives rise to an electron-hole asymmetry in the conductance and in sufficiently long junctions induces two conductance minima at the energies of the Dirac points for suspended and clamped regions, respectively. We obtain the potential profile along a junction caused by doping and provide parameters for effective model calculations of the junction conductance with weakly interacting metallic leads.


Detection and estimation of liquid flow through a pipe in a tissue-like object with ultrasound-assisted diffuse correlation spectroscopy.
Using coherent light interrogating a turbid object perturbed by a focused ultrasound (US) beam, we demonstrate localized measurement of dynamics in the focal region, termed the region-of-interest (ROI), from the decay of the modulation in intensity autocorrelation of light. When the ROI contains a pipe flow, the decay is shown to be sensitive to the average flow velocity from which the mean-squared displacement (MSD) of the scattering centers in the flow can be estimated. While the MSD estimated is seen to be an order of magnitude higher than that obtainable through the usual diffusing wave spectroscopy (DWS) without the US, it is seen to be more accurate as verified by the volume flow estimated from it. It is further observed that, whereas the MSD from the localized measurement grows with time as τ(α) with α≈1.65, without using the US, α is seen to be much less. Moreover, with the local measurement, this super-diffusive nature of the pipe flow is seen to persist longer, i.e., over a wider range of initial τ, than with the unassisted DWS. The reason for the super-diffusivity of flow, i.e., α<2, in the ROI is the presence of a fluctuating (thermodynamically nonequilibrium) component in the dynamics induced by the US forcing. Beyond this initial range, both methods measure MSDs that rise linearly with time, indicating that ballistic and near-ballistic photons hardly capture anything beyond the background Brownian motion.


An efficient procedure for the preparation of (1S,3R)- and (1S,3S)-1-amino-3-(hydroxymethyl)cyclopentanes.
Enantiomerically pure (1S,3S)- and (1S,3R)-1-amino-3-(hydroxymethyl)cyclopentanes have been efficiently synthesized from L-aspartic acid. The title compounds are isosteres of ribose and may be used to construct nucleoside analogs with important antiviral and antineoplastic activities as demonstrated by a concise total synthesis of (+)-4'-deoxycarbapentostatin nucleoside.


Structure and dynamics of soft repulsive colloidal suspensions in the vicinity of the glass transition.
We use a combination of different scattering techniques and rheology to highlight the link between structure and dynamics of dense aqueous suspensions of soft repulsive colloids in the vicinity of a glass transition. Three different latex formulations with an increasing amount of the hydrophilic component resulting in either purely electrostatically or electrosterically stabilized suspensions are investigated. From the analysis of the static structure factor measured by small-angle X-ray scattering, we derive an effective volume fraction that includes contributions from interparticle interactions. We further investigate the dynamics of the suspensions using 3D cross-correlation dynamic light scattering (3DDLS) and rheology. We analyze the data using an effective hard sphere model and in particular compare the linear viscoelasticity and flow behavior to the predictions of mode coupling theory, which accounts for a purely kinetic glass transition determined by the equilibrium structure factor. We demonstrate that seemingly very different colloidal systems exhibit the same generic behavior when the effects from interparticle interactions are incorporated using an effective volume fraction description.


School-based health centers during academic disruption: Challenges and opportunity in urban mental health.
School based health centers (SBHC) provide healthcare services to youth and their families. In response to the global health crisis from COVID-19, schools' closures have impacted the access to vital services during times of increased need for physical and mental healthcare. Youth of minority racial and ethnic backgrounds living in urban settings face compounding factors including adverse childhood events, economic disadvantages, and barriers to healthcare. The mental health response of SBHCs in New York City as it relates to population specific factors such as family supports, economic considerations, and healthcare correlates is explored. The role of school based health centers and recommendations for interventions addressing mental health concerns in youth during COVID-19 are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


The relationship between cardio-ankle vascular index and subclinical atherosclerosis evaluated by cardiac computed tomographic angiography.
The cardio-ankle vascular index (CAVI) is a new noninvasive index to evaluate arterial stiffness. We investigated whether CAVI can predict severity, extent, and burden of coronary artery disease by comparing results with cardiac computed tomographic angiography (CCTA). CAVI may predict the presence of subclinical atherosclerosis. We prospectively enrolled 95 patients (66% male; mean age, 50 ± 16 years) who underwent both CCTA and CAVI consecutively. We evaluated if CAVI correlated with (1) severe stenosis (≥50%); (2) plaque extent, determined by a segment-involvement score (SIS), defined by the total number of coronary artery segments containing any plaque; and (3) plaque burden, determined by a segment-stenosis score (SSS), defined by the extent of obstruction of coronary luminal diameter in individual coronary artery segments. Bivariate analysis showed a statistically significant relationship not only between CAVI and SIS, but also between CAVI and SSS (r2 = 0.4, P < 0.0001 for SIS; r2 = 0.36, P < 0.0001 for SSS). Multivariable logistic analysis demonstrated that CAVI is significantly associated with SSS >5 (odds ratio [OR]: 2.3, 95% confidence interval [CI]: 1.1-7.8, P = 0.03) and SIS >5 (OR: 2.3, 95% CI: 1.1-5.8, P = 0.02), but not severe stenosis (OR: 1.7, 95% CI: 0.9-4.3, P = 0.13), after adjusting for age, sex, chest pain, hypertension, dyslipidemia, family history, diabetes, and current smoking. We demonstrated that CAVI had a significant relationship with subclinical coronary atherosclerosis evaluated by CCTA, especially in relation to plaque burden and plaque extent, but not severe stenosis. Thus, CAVI may reflect coronary atherosclerosis burden more than severity.