Regulation of septum formation by the Bud3-Rho4 GTPase module in Aspergillus nidulans.
The ability of fungi to generate polarized cells with a variety of shapes likely reflects precise temporal and spatial control over the formation of polarity axes. The bud site selection system of Saccharomyces cerevisiae represents the best-understood example of such a morphogenetic regulatory system. However, the extent to which this system is conserved in the highly polarized filamentous fungi remains unknown. Here, we describe the functional characterization and localization of the Aspergillus nidulans homolog of the axial bud site marker Bud3. Our results show that AnBud3 is not required for polarized hyphal growth per se, but is involved in septum formation. In particular, our genetic and biochemical evidence implicates AnBud3 as a guanine nucleotide exchange factor for the GTPase Rho4. Additional results suggest that the AnBud3-Rho4 module acts downstream of the septation initiation network to mediate recruitment of the formin SepA to the site of contractile actin ring assembly. Our observations provide new insight into the signaling pathways that regulate septum formation in filamentous fungi.


[Metabolism of catecholamines in children with attention deficit syndrome with hyperactivity].
The aim of research was to study catecholamine excretion peculiarities of the children with attention deficit hyperactivity disorder (ADHD). 25 children at the age of 7-9 years took part in this research. High-pressure liquid chromatography (HPLC) was used for measuring the content of catecholamine. The content of catecholamine was defined in the morning samples of urine. The examination showed, that ADHD children had the basal level of epinephrine and norepinephrine more than the normal control in 3.9 and 5.4 times. After cognitive tests the content of norepinephrine reduced in the ADHD group in 2.1 times in the comparison with normal control. On the contrary content of epinephrine increased in 2.8 times. Simpatico-adrenal system hyperactivity (especially it's adrenals component) characterized ADHD children.


Monoclonal antibodies against RNA-dependent DNA polymerase from myeloblastosis-associated viruses.
Two lines of hybridomas, RT-12 and RT-14, secreting monoclonal antibodies against the reverse transcriptase from myeloblastosis-associated viruses have been prepared. The monoclonal antibodies RT-12 and RT-14 specifically react with reverse transcriptase, as has been shown by radioimmunoassay and enzyme-linked immunoassay techniques after SDS-PAGE and blotting to nitrocellulose membranes. It has been shown that antigenic determinants for RT-12 and RT-14 are stable to SDS denaturation, hence they belong to a linear type; they are located on the alpha subunit of the enzyme.


Utilization of HPASubC for the Identification of Sinusoid-Specific Proteins in the Liver.
Mass spectrometry-based proteomes of human organs and tissues are powerful tools but fail to capture protein localization and expression at the cellular level. For example, the proteome signal in liver represents the combined protein expression across diverse cellular constituents that include hepatocytes, Kupffer cells, endothelial cells, and others. We utilized HPASubC and the Human Protein Atlas (HPA) to identify the sinusoidal component of protein liver expression to further subset and organize this homogeneous signal. We evaluated 51 109 liver images covering 13 197 proteins from the HPA and discovered 1054 proteins that were exclusive to sinusoidal cells. Sinusoidal staining patterns were identified in a Kupffer cell (n = 247), endothelial cell (n = 358), or lymphocyte (n = 86) specific pattern. Two-hundred and thirty-nine of these proteins were not present in the NextProt or Human Proteome Map liver data sets, potentially expanding our knowledge of the liver proteome. We additionally demonstrate unique endothelial cell expression patterns that distinguish between portal vein, hepatic artery, capillary sinusoids, and central vein regions. These findings significantly improve our understanding of the liver proteome with insight into the endothelial complexity across the hepatic vascular network.


Glutamate 107 in subunit I of the cytochrome bd quinol oxidase from Escherichia coli is protonated and near the heme d/heme b595 binuclear center.
Cytochrome bd is a quinol oxidase from Escherichia coli, which is optimally expressed under microaerophilic growth conditions. The enzyme catalyzes the two-electron oxidation of either ubiquinol or menaquinol in the membrane and scavenges O2 at low concentrations, reducing it to water. Previous work has shown that, although cytochrome bd does not pump protons, turnover is coupled to the generation of a proton motive force. The generation of a proton electrochemical gradient results from the release of protons from the oxidation of quinol to the periplasm and the uptake of protons used to form H2O from the cytoplasm. Because the active site has been shown to be located near the periplasmic side of the membrane, a proton channel must facilitate the delivery of protons from the cytoplasm to the site of water formation. Two conserved glutamic acid residues, E107 and E99, are located in transmembrane helix III in subunit I and have been proposed to form part of this putative proton channel. In the current work, it is shown that mutations in either of these residues results in the loss of quinol oxidase activity and can result in the loss of the two hemes at the active site, hemes d and b595. One mutant, E107Q, while being totally inactive, retains the hemes. Fourier transform infrared (FTIR) redox difference spectroscopy has identified absorption bands from the COOH group of E107. The data show that E107 is protonated at pH 7.6 and that it is perturbed by the reduction of the heme d/heme b595 binuclear center at the active site. In contrast, mutation of an acidic residue known to be at or near the quinol-binding site (E257A) also inactivates the enzyme but has no substantial influence on the FTIR redox difference spectrum. Mutagenesis shows that there are several acidic residues, including E99 and E107 as well as D29 (in CydB), which are important for the assembly or stability of the heme d/heme b595 active site.


Tissue-specific defense and thermo-adaptive mechanisms of soybean seedlings under heat stress revealed by proteomic approach.
A comparative proteomic approach was employed to explore tissue-specific protein expression patterns in soybean seedlings under heat stress. The changes in the protein expression profiles of soybean seedling leaves, stems, and roots were analyzed after exposure to high temperatures. A total of 54, 35, and 61 differentially expressed proteins were identified from heat-treated leaves, stems, and roots, respectively. Differentially expressed heat shock proteins (HSPs) and proteins involved in antioxidant defense were mostly up-regulated, whereas proteins associated with photosynthesis, secondary metabolism, and amino acid and protein biosynthesis were down-regulated in response to heat stress. A group of proteins, specifically low molecular weight HSPs and HSP70, were up-regulated and expressed in a similar manner in all tissues. Proteomic analysis indicated that the responses of HSP70, CPN-60 beta, and ChsHSP were tissue specific, and this observation was validated by immunoblot analysis. The heat-responsive sHSPs were not induced by other stresses such as cold and hydrogen peroxide. Taken together, these results suggest that to cope with heat stress soybean seedlings operate tissue-specific defenses and adaptive mechanisms, whereas a common defense mechanism associated with the induction of several HSPs was employed in all three tissues. In addition, tissue-specific proteins may play a crucial role in defending each type of tissues against thermal stress.


Cutaneous manifestations of internal malignancy.
Many malignancies affecting the internal organs display cutaneous manifestations which may be either specific (tumor metastases) or nonspecific lesions. The study is aimed at determining the frequency and significance of cutaneous manifestations among patients with internal malignancy. 750 cases of proven internal malignancy, who attended a cancer chemotherapy center in South India, were studied. Specific infiltrates were confirmed by histopathology, fine needle aspiration cytology (FNAC) and marker studies. Out of the 750 patients with internal malignancy, skin changes were seen in a total of 52 (6.93%) patients. Cutaneous metastases (specific lesions) were seen in 20 patients (2.66%): contiguous in 6 (0.8%), and non-contiguous in 14 (1.86%). Nonspecific skin changes were seen in 32 patients (4.26%). None of our patients presented with more than one type of skin lesions. Herpes zoster was the most common nonspecific lesion noticed in our patients, followed by generalized pruritus, multiple eruptive seborrheic keratoses, bullous disorder, erythroderma, flushing, purpura, pyoderma gangrenosum, insect bite allergy and lichenoid dermatitis.


Family issues in home-based care.
In Australia, home-based care for the chronically ill is increasing. Technological advances and increased economic constraints are often cited as the reasons for the increase in home-based treatments. Exploring the development of home-based care, in particular home-based dialysis, using a case-study approach provided an opportunity to identify the issues of families involved in home care. Issues that emerged included: (i) the development of the home-based clinic; (ii) the role of women; (iii) social isolation; (iv) and the lack of effective support from general practitioners and health services.


Higher Neuronal Facilitation and Potentiation with APOE4 Suppressed by Angiotensin II.
Progressive hippocampal degeneration is a key component of Alzheimer's disease (AD) progression. Therefore, identifying how hippocampal neuronal function is modulated early in AD is an important approach to eventually prevent degeneration. AD-risk factors and signaling molecules likely modulate neuronal function, including APOE genotype and angiotensin II. Compared to APOE3 , APOE4 increases AD risk up to 12-fold, and high levels of angiotensin II are hypothesized to disrupt neuronal function in AD. However, the extent that APOE and angiotensin II modulates the hippocampal neuronal phenotype in AD-relevant models is unknown. To address this issue, we used electrophysiological techniques to assess the impact of APOE genotype and angiotensin II on basal synaptic transmission, presynaptic and post-synaptic activity in mice that express human APOE3 (E3FAD) or APOE4 (E4FAD) and overproduce Aβ. We found that compared to E3FAD mice, E4FAD mice had lower basal synaptic activity, but higher levels of paired pulse facilitation (PPF) and Long-Term Potentiation (LTP) in the Schaffer Collateral Commissural Pathway (SCCP) of the hippocampus. We also found that exogenous angiotensin II has a profound inhibitory effect on hippocampal LTP in both E3FAD and E4FAD mice. Collectively, our data suggests that APOE4 and Aβ are associated with a hippocampal phenotype comprised of lower basal activity and higher responses to high frequency stimulation, the latter of which is suppressed by angiotensin II. These novel data suggest a potential mechanistic link between hippocampal activity, APOE4 genotype and angiotensin II in AD.


First report of Anopheles stephensi from southern Ethiopia.
Anopheles stephensi is an emerging exotic invasive urban malaria vector in East Africa. The World Health Organization recently announced an initiative to take concerted actions to limit this vector's expansion by strengthening surveillance and control in invaded and potentially receptive territories in Africa. This study sought to determine the invasion of An. stephensi in southern Ethiopia. A targeted entomological survey, both larvae and adult, was conducted in Hawassa City, southern Ethiopia between November 2022 and February 2023. Anopheles larvae were reared to adults for species identification. CDC light traps and BG Pro traps were used indoors and outdoors overnight at selected houses to collect adult mosquitoes in the study area. Prokopack aspirator was employed to sample indoor resting mosquitoes in the morning. Adults of An. stephensi was identified using morphological keys and then confirmed by PCR. Larvae of An. stephensi were found in 28 (16.6%) of the 169 potential mosquito breeding sites surveyed. Out of 548 adult female Anopheles mosquitoes reared from larvae, 234 (42.7%) were identified as An. stephensi morphologically. A total of 449 female anophelines were caught, of which 53 (12.0%) were An. stephensi. Other anopheline species collected in the study area included Anopheles gambiae sensu lato (s.l.), Anopheles pharoensis, Anopheles coustani, and Anopheles demeilloni. This study confirmed the presence of An. stephensi in southern Ethiopia. The presence of both larval and adult stages of this mosquito attests that this species established sympatric colonization with native vector species such as An. gambiae (s.l.) in southern Ethiopia. The findings warrant further investigation on the ecology, behaviour, population genetics, and role of An. stephensi in malaria transmission in Ethiopia.


Role of MRI in the diagnosis of clinically suspected scaphoid fracture: analysis of 611 consecutive cases and literature review.
A clinically suspected scaphoid fracture with normal initial plain x-rays is a difficult but common problem. The role of MRI as a diagnostic modality in this situation was analysed based on the experience of 611 consecutive cases. All patients presenting to the emergency department with a history of a fall on an outstretched hand and with tenderness over the anatomical snuff box and scaphoid tubercle but normal plain x-rays were offered MRI as part of the standard protocol. Between January 2003 and November 2005, 611 of a total of 619 such patients underwent the scan and form the study cohort. Coronal 3 mm T1 and Short Tau Inversion Recovery images were obtained using a 12 cm field of view as standard. There were 342 abnormal scans (56%) and 269 (44%) normal scans. Of the abnormal scans, 80% showed acute bony injuries, 8% showed acute soft tissue injuries and 12% showed incidental pathology. MRI is a useful and effective tool in the diagnosis of radiologically occult wrist injuries. It is feasible to do MRI scans in a timely manner in a district general hospital.


Finding Common Ground and Advancing Engagement in Citizen Science.
Citizen science, a diverse enterprise involving multiple processes, participants, and projects, challenges conventional approaches to thinking about science and the issues it raises. This commentary explores three key themes identified in the accompanying narratives. (1) Motivated volunteers may serve as novel resources for science, allowing projects to proceed in ways that are cheaper and more accessible than previously considered. (2) Traditional scientific approaches may be insufficient to even identify research questions, much less attempt to address issues. Citizen science may fill that gap. (3) Ethical concepts may have unique applications in this burgeoning field, both due to the emergence of novel ethical issues and to new categories of people, places, and things inherent in the conduct of citizen science. The commentary closes with suggestions for moving forward as citizen science becomes the norm rather than the exception.


A GluN2B-Selective NMDAR Antagonist Reverses Synapse Loss and Cognitive Impairment Produced by the HIV-1 Protein Tat.
HIV-associated neurocognitive disorder (HAND) affects approximately half of HIV-infected patients. Loss of synaptic connections is a hallmark of many neurocognitive disorders, including HAND. The HIV-1 protein transactivator of transcription (Tat) disrupts synaptic connections both in vitro and in vivo and has been linked to impaired neurocognitive function in humans. In vitro studies have shown that ifenprodil, an antagonist selective for GluN2B-containing NMDARs, reverses synapse loss when applied after Tat. Here, we tested the hypothesis that Tat-induced loss and ifenprodil-mediated rescue of synaptic spines in vivo would predict impairment and rescue of cognitive function. Using intracranial multiphoton imaging, we found that infusion of 100 ng of HIV-1 Tat into the lateral ventricle of yellow fluorescent protein-expressing transgenic mice produced a 17 ± 1% loss of dendritic spines in layer 1 of retrosplenial cortex. Repeated imaging of the same dendrites over 3 weeks enabled longitudinal experiments that demonstrated sustained spine loss after Tat infusion and transient rescue after ifenprodil administration (10 mg/kg, i.p.). Parallel trace fear conditioning experiments showed that spine loss predicted learning deficits and that the time course of ifenprodil-induced rescue of spine density correlated with restoration of cognitive function. These results show for the first time that, during exposure to an HIV-1 neurotoxin in vivo, alteration of GluN2B-containing NMDAR signaling suppresses spine density and impairs learning. Pharmacological inhibition of these NMDARs rescued spines and restored cognitive function. Drugs that rescue synapses may improve neurocognitive function in HAND.SIGNIFICANCE STATEMENT Synaptodendritic damage correlates with cognitive decline in HIV-associated neurocognitive disorder (HAND) patients. We developed an in vivo imaging approach for longitudinal tracking of spine density that enabled correlation of synaptic changes with behavioral outcomes in a model of HAND. We show for the first time that spine loss after exposure to an HIV-1 protein can be reversed pharmacologically and that loss and recovery of dendritic spines predict impairment and restoration of cognitive function, respectively. Therefore, synapse loss, the hallmark of cognitive decline in HAND, is reversible. Drugs that restore spine density may have broad application for improving cognitive function during the early phases of neurodegenerative diseases.


Accelerated antimicrobial discovery via deep generative models and molecular dynamics simulations.
The de novo design of antimicrobial therapeutics involves the exploration of a vast chemical repertoire to find compounds with broad-spectrum potency and low toxicity. Here, we report an efficient computational method for the generation of antimicrobials with desired attributes. The method leverages guidance from classifiers trained on an informative latent space of molecules modelled using a deep generative autoencoder, and screens the generated molecules using deep-learning classifiers as well as physicochemical features derived from high-throughput molecular dynamics simulations. Within 48 days, we identified, synthesized and experimentally tested 20 candidate antimicrobial peptides, of which two displayed high potency against diverse Gram-positive and Gram-negative pathogens (including multidrug-resistant Klebsiella pneumoniae) and a low propensity to induce drug resistance in Escherichia coli. Both peptides have low toxicity, as validated in vitro and in mice. We also show using live-cell confocal imaging that the bactericidal mode of action of the peptides involves the formation of membrane pores. The combination of deep learning and molecular dynamics may accelerate the discovery of potent and selective broad-spectrum antimicrobials.


Dunnock social status correlates with sperm speed, but fast sperm does not always equal high fitness.
Sperm competition theory predicts that males should modulate sperm investment according to their social status. Sperm speed, one proxy of sperm quality, also influences the outcome of sperm competition because fast sperm cells may fertilize eggs before slow sperm cells. We evaluated whether the social status of males predicted their sperm speed in a wild population of dunnocks (Prunella modularis). In addition to the traditional analysis of the average speed of sperm cells per sample, we also analysed subsamples of the fastest sperm cells per sample. In other words, we systematically evaluated the effects of including different numbers of the fastest sperm in our analyses, ranging from the 5-fastest sperm cells to the 100-fastest sperm cells in a sample. We further evaluated whether fitness, defined here as the number of chicks sired per male per breeding season, relates to the sperm speed in the same population. We found that males in monogamous pairings (i.e. low levels of sperm competition), produced the slowest sperm cells, whereas subordinate males in polyandrous male-male coalitions (i.e. high levels of sperm competition) produced the fastest sperm cells. This result was consistent regardless of the number of fastest sperm included in our analyses, but statistical support was conditional on the number of sperm cells included in the analysis. Interestingly, we found no significant relationship between fitness and sperm speed, which suggests that it is possible that the differential mating opportunities across social status levelled out any possible difference. Our study also suggests that it is important to identify biologically meaningful subsets of fastest sperm and cut-offs for inclusions for assessing sperm competition via sperm speed.


In vivo molecular imaging of cathepsin and matrix metalloproteinase activity discriminates between arthritic and osteoarthritic processes in mice.
Rheumatoid arthritis (RA) and osteoarthritis (OA) are serologically and clinically distinctive, but at the local level, both diseases have many molecular pathways in common. In vivo molecular imaging can unravel the local pathologic processes involved in both diseases. In this study, we investigated matrix metalloproteinase (MMP) and cathepsin activity during cartilage destruction, in an RA and an OA mouse model, using biophotonic imaging of substrate-based probes. Mice with collagen-induced arthritis (CIA) or destabilization of the medial meniscus (DMM) were imaged using near-infrared fluorescent probes, activated by several cathepsins or MMPs. Fluorescence signal intensity was compared to synovial gene expression, histology, and cartilage staining of a neoepitope of aggrecan cleaved by MMPs with the amino acids DIPEN. Increased cathepsin and MMP activity was seen during CIA, whereas the DMM model only showed increased MMP activity. DIPEN expression was seen only during CIA. A possible explanation can be differences in gene expressions; MMP3 and -13, known to produce DIPEN neoepitopes, were upregulated in the CIA model, whereas MMP12, known to be involved in elastin degradation and chemokine inhibition, was upregulated in the DMM model. Thus, molecular imaging showed no cathepsin activity at the time of cartilage damage in the DMM model, whereas both cathepsins and MMPs are active in the CIA model during disease progression.


The chronic effects of alcohol on memory. A contrast between a unitary and dual system approach.
Recent studies have indicated that impairment of memory is a common cognitive deficit related to long-term alcohol consumption. Such deficits range from subtle disturbance through a "subclinical" amnesic disorder to full-blown Korsakoff syndrome. This finding is congenial with the hypothesized continuum of alcohol-related impairment of memory. Among alcoholics, this memory impairment appears to be etiologically distinct from the commonly observed deficits in abstracting and problem-solving abilities. In the present chapter, a dual and a unitary formulation of memory are contrasted in their ability to present a coherent account of what memory tasks Korsakoff amnesics can and cannot do. The explanations offered by unitary theory are weak compared to those derived from the theory that memory consists of two distinct systems--experiential and abstractive memory. We indicate how the pattern of responding on standard clinical tests of memory can be coherently analyzed post hoc within the dual formulation. A number of experimental predictions are also presented based on the theory that Korsakoff amnesics have a profound impairment of experiential memory, whereas the abstractive system is essentially normal. Such experiments should clarify the nature both of Korsakoff amnesia and of memory itself. In conclusion, we indicated that memory disorders related to alcoholism can be understood in terms of a gradient, or continuum, of impairment of the experiential system.


Magnetocardiograms in clinical medicine: unique information on cardiac ischemia, arrhythmias, and fetal diagnosis.
Cardiac diseases are the leading cause of death in population. Diagnostic tests to detect cardiac dysfunction at an early stage of the disease are desirable. The major focus has been centered on tests evaluating the perfusion of the heart with imaging techniques or detecting alterations in electrical or mechanical function of the heart. The heart generates magnetic fields that can be detected by body surface mapping utilizing super conducting quantum interference device sensors giving magnetocardiograms (MCGs). The advantages of MCG over traditional electrocardiograms (ECGs) are increased sensitivity to small signals and lack of conductivity in body tissues, presentation of direct component signals and primary currents. This review will highlight the basic principles and recent advantages of MCGs, and the application of MCG in clinical diagnosis, especially in cases whose ECGs are non-diagnostic or not specific, such as detecting baseline shift in ischemic heart disease, noninvasive His potential recording, detection of arrhythmic mechanism defining reentrant circuits vs non reentrant mechanism, diagnosis of fetal arrhythmias and prolongation of QT interval. Areas of future basic and clinical research are also discussed.


Morphometric studies in human pancreatic cancer argues against the etiological role of type 2 diabetes in pancreatic cancer.
To understand the role of islet amyloid polypeptide (IAPP) in type 2 diabetes and pancreatic cancer (PC), we investigated the patterns of its expression and its ratio to insulin, glucagon, somatostatin and pancreatic polypeptide cells by morphometry in tissues from these two diseases in comparison to the normal pancreas. Pancreatic tissues from 11 donors (five without pancreatic disease and six with type 2 diabetes) and 11 surgical specimens from PC patients obtained from the cancer area (zone A) and the adjacent tumor-free area (zone B) were examined immunohistochemically. The size of islets, the number on beta-, alpha-, delta- pp- and IAPP-expressing cells and their ratios in the islets of these tissues were determined. In the normal pancreas, only 50% of the beta-cells while alpha- and delta-cells co-expressed IAPP only sporadically. In tissues from diabetics as well as in zone A, the number of the beta-cells and the IAPP-expressing cells was reduced significantly, while the number of alpha- and delta-cells was increased. In zone B, however, significantly more beta-cell and IAPP-expressing cells and a significantly lower number of alpha-cells were found compared to those in zone A. Significant differences were also found between the specimens from type 2 diabetics and pancreatic cancer relative to the ratios of IAPP/beta-cell, IAPP/alpha-cells and beta-cell/delta-cells. The morphometric data show a decrease rather than an increase in the number of IAPP-expressing cells in PC. Differences in abnormalities in type-2 diabetics and in zone B of PC tissue strongly argue against the role of type 2 diabetes in PC. Rather, the development of diabetes in subjects prone to pancreatic cancer could be a red flag for malignancy.


The bittersweet taste of sacrifice: Consequences for ambivalence and mixed reactions.
People in close relationships often need to sacrifice their own preferences and goals for the partner or the relationship. But what are the consequences of such sacrifices for relationship partners? In this work we provide a systematic investigation of the consequences of sacrifice in romantic relationships, both for the person who gives up their goals as well as for the recipient of these benefits. In 5 studies combining experience sampling and experimental methods, we examined whether performing and receiving sacrifices is linked to the experience of ambivalence, that is, mixed feelings toward a partner. In the last 3 studies, we also examined the specific positive and negative reactions associated with sacrifice. Results revealed that performing and receiving sacrifices are both linked to ambivalence toward a romantic partner. Recipients of sacrifices experienced higher negative mood, guilt, and feelings of indebtedness, but these were accompanied by higher positive mood, gratitude, and feeling appreciated by the partner. Sacrificers mostly experienced negative reactions, such as higher negative mood, frustration, and feelings of exploitation, but they also reported some positive reactions, such as feeling happy from benefitting their partner, proud of themselves for being a good partner, and had increased expectations that their partner would reciprocate the sacrifice in the future. In sum, this work provides the first comprehensive study of the emotional reactions that are triggered by sacrifice and shows that sacrifice is a double-edged sword with both positive and negative consequences. Implications for sacrifice and ambivalence are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Circumventing AKT-Associated Radioresistance in Oral Cancer by Novel Nanoparticle-Encapsulated Capivasertib.
Development of radioresistance in oral squamous cell carcinoma (OSCC) remains a significant problem in cancer treatment, contributing to the lack of improvement in survival trends in recent decades. Effective strategies to overcome radioresistance are necessary to improve the therapeutic outcomes of radiotherapy in OSCC patients. Cells and xenograft tumors were irradiated using the Small Animal Radiation Research Platform. AKT inhibitor capivasertib (AZD5363) was encapsulated into cathepsin B-responsible nanoparticles (NPs) for tumor-specific delivery. Cell viability was measured by alamarBlue, cell growth was determined by colony formation and 3D culture, and apoptosis was assessed by flow cytometry with the staining of Fluorescein isothiocyanate (FITC) Annexin V and PI. An orthotopic tongue tumor model was used to evaluate the in vivo therapeutic effects. The molecular changes induced by the treatments were assessed by Western blotting and immunohistochemistry. We show that upregulation of AKT signaling is the critical mechanism for radioresistance in OSCC cells, and AKT inactivation by a selective and potent AKT inhibitor capivasertib results in radiosensitivity. Moreover, relative to irradiation (IR) alone, IR combined with the delivery of capivasertib in association with tumor-seeking NPs greatly enhanced tumor cell repression in 3D cell cultures and OSCC tumor shrinkage in an orthotopic mouse model. These data indicate that capivasertib is a potent agent that sensitizes radioresistant OSCC cells to IR and is a promising strategy to overcome failure of radiotherapy in OSCC patients.


[Home medical care network in the community supporting hospital--nursing consultant acting for community coordination].
Tama Nambu-Chiiki Hospital is a secondary medical institution providing the acute short-term care centered on cancer treatment and emergency medical service, which few other medical institutions in the region provide. The hospital, which has no system to directly support home medical care by house visit or visiting nurses, needs to coordinate home medical care with other community medical institutions. 2 nurses serve as the Nursing Consultants who provide consultation services over the issues related to home medical care and other issues face to face or by phone and coordinate home medical care with other community medical institutions. Medical coordination based on trust and understanding of home medical care by hospital staffs are essential for the smooth transfer to home medical care. Activities of the hospital are studied to cope with the changes in healthcare trend.


Reconstruction and assessment of the least-squares and slope discrepancy components of the phase.
The concept of slope discrepancy developed in the mid-1980's to assess measurement noise in a wave-front sensor system is shown to have additional contributions that are due to fitting error and branch points. This understanding is facilitated by the development of a new formulation that employs Fourier techniques to decompose the measured gradient field (i.e., wave-front sensor measurements) into two components, one that is expressed as the gradient of a scalar potential and the other that is expressed as the curl of a vector potential. A key feature of the theory presented here is the fact that both components of the phase (one corresponding to each component of the gradient field) are easily reconstructable from the measured gradients. In addition, the scalar and vector potentials are both easily expressible in terms of the measured gradient field. The work concludes with a wave optics simulation example that illustrates the ease with which both components of the phase can be obtained. The results obtained illustrate that branch point effects are not significant until the Rytov number is greater than 0.2. In addition, the branch point contribution to the phase not only is reconstructed from the gradient data but is used to illustrate the significant performance improvement that results when this contribution is included in the correction applied by an adaptive optics system.


Degradation of S-RNase in compatible pollen tubes of Solanum chacoense inferred by immunogold labeling.
The flowering plant Solanum chacoense uses an S-RNase-based self-incompatibility system in order to reject pollen that shares the same genes at the S-locus (S-haplotype) with the style (an incompatible reaction). Two different models have been advanced to explain how compatible pollen tubes are protected from the cytotoxic effects of the S-RNase, sequestration of the S-RNase in a vacuolar compartment or degradation of the S-RNase in the cytoplasm. Here, we examine the subcellular distribution of an S11-RNase 18 and 24 h post pollination (hpp) in compatible and incompatible crosses by immunogold labeling and transmission electron microscopy. We find that the S-RNase is present in the cytoplasm of both compatible and incompatible crosses by 18 hpp, but that almost all the cytoplasmic S-RNase is degraded by 24 hpp in compatible crosses. These results provide compelling evidence that S-RNases are degraded in compatible but not in incompatible pollen tubes.


Limbal stem cell transplantation: current perspectives.
Regeneration of the corneal surface after an epithelial insult involves division, migration, and maturation of a specialized group of stem cells located in the limbus. Several insults, both intrinsic and extrinsic, can precipitate destruction of the delicate microenvironment of these cells, resulting in limbal stem cell deficiency (LSCD). In such cases, reepithelialization fails and conjunctival epithelium extends across the limbus, leading to vascularization, persistent epithelial defects, and chronic inflammation. In partial LSCD, conjunctival epitheliectomy, coupled with amniotic membrane transplantation, could be sufficient to restore a healthy surface. In more severe cases and in total LSCD, stem cell transplantation is currently the best curative option. Before any attempts are considered to perform a limbal stem cell transplantation procedure, the ocular surface must be optimized by controlling causative factors and comorbid conditions. These factors include adequate eyelid function or exposure, control of the ocular surface inflammatory status, and a well-lubricated ocular surface. In cases of unilateral LSCD, stem cells can be obtained from the contralateral eye. Newer techniques aim at expanding cells in vitro or in vivo in order to decrease the need for large limbal resection that may jeopardize the "healthy" eye. Patients with bilateral disease can be treated using allogeneic tissue in combination with systemic immunosuppressive therapy. Another emerging option for this subset of patients is the use of noncorneal cells such as mucosal grafts. Finally, the use of keratoprosthesis is reserved for patients who are not candidates for any of the aforementioned options, wherein the choice of the type of keratoprosthesis depends on the severity of the disease. In summary, limbal stem cell transplantation improves both vision and quality-of-life in patients with ocular surface disorders associated with LSCD, and overall, the use of autologous tissue offers the best results. Future studies aim at improving cellular expansion and finding different sources of stem cells.


Randomized Controlled-Feeding Study of Dietary Emulsifier Carboxymethylcellulose Reveals Detrimental Impacts on the Gut Microbiota and Metabolome.
Epidemiologic and murine studies suggest that dietary emulsifiers promote development of diseases associated with microbiota dysbiosis. Although the detrimental impact of these compounds on the intestinal microbiota and intestinal health have been demonstrated in animal and in vitro models, impact of these food additives in healthy humans remains poorly characterized. To examine this notion in humans, we performed a double-blind controlled-feeding study of the ubiquitous synthetic emulsifier carboxymethylcellulose (CMC) in which healthy adults consumed only emulsifier-free diets (n = 9) or an identical diet enriched with 15 g per day of CMC (n = 7) for 11 days. Relative to control subjects, CMC consumption modestly increased postprandial abdominal discomfort and perturbed gut microbiota composition in a way that reduced its diversity. Moreover, CMC-fed subjects exhibited changes in the fecal metabolome, particularly reductions in short-chain fatty acids and free amino acids. Furthermore, we identified 2 subjects consuming CMC who exhibited increased microbiota encroachment into the normally sterile inner mucus layer, a central feature of gut inflammation, as well as stark alterations in microbiota composition. These results support the notion that the broad use of CMC in processed foods may be contributing to increased prevalence of an array of chronic inflammatory diseases by altering the gut microbiome and metabolome (ClinicalTrials.gov, number NCT03440229).


Characterization of promoter elements of the rabbit cardiac sarcoplasmic reticulum Ca(2+)-ATPase gene required for expression in cardiac muscle cells.
The sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) plays a critical role in the contractile performance of cardiac and slow-twitch skeletal muscle by restoring cytosolic calcium to low resting levels during the contractile cycle. We have previously shown that SERCA2 expression in the heart is altered by a number of pathophysiological stimuli. In an effort to define molecular mechanisms regulating expression of the SERCA2 gene in cardiac muscle cells, deletions of a 1460-bp promoter fragment were generated and inserted into a luciferase reporter plasmid. Promoter constructs were transiently transfected into embryonic cardiocytes and skeletal muscle cell lines Sol 8 and C2C12 in vitro and injected into adult myocardium in vivo. Results demonstrate that sequences from the transcription start site to -284 are both necessary and sufficient for high-level transcription of the reporter gene in differentiating muscle cells and in fetal cardiocytes in culture. We further demonstrate that this promoter fragment is highly active in vivo when injected into rat hearts, suggesting that the same regulatory elements are functional in vivo as well as in vitro. The region of the gene from -284 to -658 exerts a modest positive effect in cardiocytes and Sol 8 myotubes but exerts a negative effect in C2C12 fast skeletal muscle cells. This initial analysis of transcriptional regulation of the SERCA2 gene will serve as a foundation for the study of alterations of expression of the gene in pathological conditions.


[Treatment of duodenal ulcer associated with chronic gastric erosions].
Three groups of patients received chemotherapy for duodenal ulcer and associated chronic gastric erosion. Group I was treated by the drugs combination (methacin, almagel, gastrofarm, solcoseryl, tazepam, rudotel), group II received gastrocepin, group III venter. The results of duodenal ulcer healing were similar in all the groups, yet epigastric and/or pyloroduodenal pain was relieved more rapidly in groups II and III. The latter groups were also characterized by accelerated disappearance of fibrinous patches on the surface of the erosion.


Increasing fruit and vegetable intake among children: comparing long-term effects of a free distribution and a multicomponent program.
The aim of this study was to evaluate and compare the effectiveness of two primary school-based interventions on children's fruit and vegetable (F&V) consumption on the long term (2 years after the start of the interventions). Six primary schools were recruited and randomly assigned to (i) a daily free distribution program for the whole school or (ii) a multicomponent program consisting of a classroom curriculum and parental involvement (without free F&V), and six schools served as controls. Follow-up measurements were conducted at the end of the intervention (Follow-up I) and 1 year later (Follow-up II). Random coefficient analyses for longitudinal data showed that the effects of both interventions did not differ between the two follow-up measurements. The results showed similar effects for the free distribution program and the multicomponent program in increasing children's fruit consumption over time (respectively, 7.2 and 15.2 g day(-1)). The distribution program also increased children's vegetable consumption over time (3.25 g day(-1)), even after repeating the analyses using a pessimistic scenario. Despite the large dropout and its consequences for generalizability of our results, the distribution program is considered as the preferred intervention of the two, and implementation on a larger scale should be investigated.


Past, Present, and Future of Neurosurgery in Uganda.
Neurosurgery in Uganda was virtually non-existent up until late 1960s. This changed when Dr. Jovan Kiryabwire spearheaded development of a neurosurgical unit at Mulago Hospital in Kampala. His work ethic and vision set the stage for rapid expansion of neurosurgical care in Uganda.At the beginning of the 2000s, Uganda was a country of nearly 30 million people, but had only 4 neurosurgeons. Neurosurgery's progress was plagued by challenges faced by many developing countries, such as difficulty retaining specialists, lack of modern hospital resources, and scarce training facilities. To combat these challenges 2 distinct programs were launched: 1 by Dr. Benjamin Warf in collaboration with CURE International, and the other by Dr. Michael Haglund from Duke University. Dr. Warf's program focused on establishing a facility for pediatric neurosurgery. Dr. Haglund's program to increase neurosurgical capacity was founded on a "4 T's Paradigm": Technology, Twinning, Training, and Top-Down. Embedded within this paradigm was the notion that Uganda needed to train its own people to become neurosurgeons, and thus Duke helped establish the country's first neurosurgery residency training program.Efforts from overseas, including the tireless work of Dr. Benjamin Warf, have saved thousands of children's lives. The influx of the Duke Program caused a dynamic shift at Mulago Hospital with dramatic effects, as evidenced by the substantial increase in neurosurgical capacity. The future looks bright for neurosurgery in Uganda and it all traces back to a rural village where 1 man had a vision to help the people of his country.


A method for consistent cavitation bubble generation at different voltages.
A study of the dynamics of a single cavitation bubble is fundamental for understanding a wide range of applications in science and engineering. Underwater electrical discharge is a widely used method for generating cavitation bubbles to study their inception, subsequent dynamics, and collapse. In this work, an existing underwater low-voltage discharge circuit for generating cavitation bubbles is improved further to get a wider range of maximum bubble radius. In this novel electric circuit design, the operating voltage can be varied (up to 420 V in steps of 60 V) by connecting a network of capacitors in different series-parallel combinations with the help of relay-based control. Therefore, this device can generate oscillating cavitation bubbles up to a maximum radius of 14 mm by adjusting the available discharge energy. A voltage sensor circuit is included in this design to measure the drop in voltage during the sparking event, and a correlation between the delivered energy and the potential energy of the bubble is established. The dependence of bubble radius on circuit resistance, electrode resistance, and electrode material is studied for the entire voltage range. A suitably rated semiconductor field effect transistor is used as a switch that enables the generation of bubbles of a consistent maximum radius and ensures the repeatability of the experiment. A high-speed imaging system is used to estimate the bubble radius and nucleation period, which are compared with the existing theoretical models based on empty cavity collapse. Results show that delaying the oxidation of electrodes with a protective layer influences the collapse phase and the average pressure inside the spark-generated bubble.


Pashto offensive language detection: a benchmark dataset and monolingual Pashto BERT.
Social media platforms have become inundated with offensive language. This issue must be addressed for the growth of online social networks (OSNs) and a healthy online environment. While significant research has been devoted to identifying toxic content in major languages like English, this remains an open area of research in the low-resource Pashto language. This study aims to develop an AI model for the automatic detection of offensive textual content in Pashto. To achieve this goal, we have developed a benchmark dataset called the Pashto Offensive Language Dataset (POLD), which comprises tweets collected from Twitter and manually classified into two categories: "offensive" and "not offensive". To discriminate these two categories, we investigated the classic deep learning classifiers based on neural networks, including CNNs and RNNs, using static word embeddings: Word2Vec, fastText, and GloVe as features. Furthermore, we examined two transfer learning approaches. In the first approach, we fine-tuned the pre-trained multilingual language model, XLM-R, using the POLD dataset, whereas, in the second approach, we trained a monolingual BERT model for Pashto from scratch using a custom-developed text corpus. Pashto BERT was then fine-tuned similarly to XLM-R. The performance of all the deep learning and transformer learning models was evaluated using the POLD dataset. The experimental results demonstrate that our pre-trained Pashto BERT model outperforms the other models, achieving an F1-score of 94.34% and an accuracy of 94.77%.


Comorbidities Incorporated to Improve Prediction for Prevalent Mild Cognitive Impairment and Alzheimer's Disease in the HABS-HD Study.
Blood biomarkers have the potential to transform Alzheimer's disease (AD) diagnosis and monitoring, yet their integration with common medical comorbidities remains insufficiently explored. This study aims to enhance blood biomarkers' sensitivity, specificity, and predictive performance by incorporating comorbidities. We assess this integration's efficacy in diagnostic classification using machine learning, hypothesizing that it can identify a confident set of predictive features. We analyzed data from 1,705 participants in the Health and Aging Brain Study-Health Disparities, including 116 AD patients, 261 with mild cognitive impairment, and 1,328 cognitively normal controls. Blood samples were assayed using electrochemiluminescence and single molecule array technology, alongside comorbidity data gathered through clinical interviews and medical records. We visually explored blood biomarker and comorbidity characteristics, developed a Feature Importance and SVM-based Leave-One-Out Recursive Feature Elimination (FI-SVM-RFE-LOO) method to optimize feature selection, and compared four models: Biomarker Only, Comorbidity Only, Biomarker and Comorbidity, and Feature-Selected Biomarker and Comorbidity. The combination model incorporating 17 blood biomarkers and 12 comorbidity variables outperformed single-modal models, with NPV12 at 92.78%, AUC at 67.59%, and Sensitivity at 65.70%. Feature selection led to 22 chosen features, resulting in the highest performance, with NPV12 at 93.76%, AUC at 69.22%, and Sensitivity at 70.69%. Additionally, interpretative machine learning highlighted factors contributing to improved prediction performance. In conclusion, combining feature-selected biomarkers and comorbidities enhances prediction performance, while feature selection optimizes their integration. These findings hold promise for understanding AD pathophysiology and advancing preventive treatments.


Teneurins instruct synaptic partner matching in an olfactory map.
Neurons are interconnected with extraordinary precision to assemble a functional nervous system. Compared to axon guidance, far less is understood about how individual pre- and postsynaptic partners are matched. To ensure the proper relay of olfactory information in the fruitfly Drosophila, axons of ∼50 classes of olfactory receptor neurons (ORNs) form one-to-one connections with dendrites of ∼50 classes of projection neurons (PNs). Here, using genetic screens, we identified two evolutionarily conserved, epidermal growth factor (EGF)-repeat containing transmembrane Teneurin proteins, Ten-m and Ten-a, as synaptic-partner-matching molecules between PN dendrites and ORN axons. Ten-m and Ten-a are highly expressed in select PN-ORN matching pairs. Teneurin loss- and gain-of-function cause specific mismatching of select ORNs and PNs. Finally, Teneurins promote homophilic interactions in vitro, and Ten-m co-expression in non-partner PNs and ORNs promotes their ectopic connections in vivo. We propose that Teneurins instruct matching specificity between synaptic partners through homophilic attraction.


Rates and predictors of sexual aggression among students and non-students.
The authors compared rates and predictors of sexual aggression for women attending college with those of women from the same population who were not attending college. Because it has been suggested that less parental monitoring at college may be associated with risky behaviors that contribute to sexual aggression, they also compared rates and predictors of sexual aggression for those living with parents versus not living with parents. The results showed that women living away from parents reported significantly higher rates of sexual aggression than women living with parents, regardless of student status. Logistic regression analyses showed that for student and non-student women, heavy episodic drinking and number of sex partners predicted past-year rape and/or attempted rape. The current results do not provide evidence that college is a uniquely risky environment for experiencing sexual aggression. Rather, the behaviors in which young women engage are associated with sexual aggression during this time period.


Different Risk Profiles for the Postsurgical Prognosis of Gastric Cancer Patients with Different Blood Types: The FIESTA Study.
Objectives: We here attempted to evaluate the prediction of different "ABO" blood groups for postsurgical gastric cancer-specific mortality by using data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. Methods: Initially, a total of 3413 patients with gastric cancer were consecutively enrolled between January 2000 and December 2010 to receive radical gastrectomy, and they were followed up until December 2015. Study patients were divided into the "O+" group and the blood type "O-" group. Results: Of 2781 eligible patients, 1116 (40.1%) were in the "O+" group and 1665 (59.9%) in the "O-" group, with mortality rate of being 45.0% (n = 502) and 45.3% (n = 755), respectively. A 1:1 propensity score match between the "O+" and the "O-" groups was used. After adjustment, neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), high total cholesterol and high low-density lipoprotein cholesterol, had non-overlapping 95% confidence intervals between the "O+" and the "O-" groups and simultaneously had detectable statistical significance in either group only. A forward method in the multivariate-adjusted COX model was employed and there were five shared risk factors between both groups, including diabetes mellitus, low high-density lipoprotein cholesterol, regional lymph node metastasis, tumor size and TNM stage. Further nomogram plot revealed that presurgical risk factors selected can better predict the risk of early gastric cancer-specific mortality (C-index: 0.737 for the "O-" group and 0.751 for the "O+" group). Conclusions: Our findings indicated that the prognostic factors differed between postsurgical gastric cancer patients with "O+" and "O-" blood types.


[Understanding heart failure].
Heart failure is a disease with several definitions. The term "heart failure" is used by has brougth about confusion in the terminology. For this reason, the value of the ejection fraction (< 0.40 or < 0.35) is used in most meganalyses on the treatment of heart failure, avoiding the term "heart failure" that is a confounding concept. In this paper we carefully analyze the meaning of contractility, ventricular function or performance, preload, afterload, heart failure, compensation mechanisms in heart failure, myocardial oxygen consumption, inadequate, adequate and inappropriate hypertrophy, systole, diastole, compliance, problems of relaxation, and diastolic dysfunction. Their definitions are supported by the original scientific descriptions in an attempt to clarify the concepts about ventricular function and heart failure and, in this way, use the same scientific language about the meaning of ventricular function, heart failure, and diastolic dysfunction.


Brief report: the medical care of adults with autism spectrum disorders: identifying the needs.
There is a lack of information concerning adults with autism spectrum disorder (ASD), especially with regards to their access to health care. A paper and electronic survey was sent to 1,580 primary care physicians in Connecticut. 346 respondents returned a survey and provided care to adults with an ASD. This physician survey provides data on adults with ASD such as: reasons for physician visits, living arrangements, employment status, and any services they are receiving. Responses revealed inadequate training in the care of adults with an ASD and physicians interest in obtaining additional training. The ability to provide a medical home for adults with autism will need to address effective strategies to train current and future physicians.


Intra-articular use of analgesic/antinflammatory drugs in dogs and horses.
Joint pain is a major cause of lameness in animals such as horses and dogs, and it may affect their athletic performance and quality of life. The intra-articular administration of analgesic/antinflammatory drugs is a common practice in veterinary medicine, for both lameness diagnosis and joint pain management. It is used either perioperatively, such as in animals undergoing arthroscopy/arthrotomy, and in osteoarthritic animals. However, evidence regarding efficacy and safety of each drug is limited, and controversies persist in these areas. In particular, it is often uncertain whether a defined treatment is effective by simply relieving the symptomatic pain associated with the joint disease, or whether it has a positive effect on the joint environment. Moreover, there is still much hesitation about treatments for joint diseases, related to the time of their application for the best outcome, and to any possible deleterious side effects. This article includes a review of the literature concerning the main analgesic/antinflammatory drugs used intra-articularly for managing acute and chronic joint pain/inflammation in dogs and horses. Three main issues for each class of drugs are considered, including clinical efficacy, pharmacokinetics, and local cytotoxic effects.


Etiology of microglial nodules in brains of patients with acquired immunodeficiency syndrome.
Microglial nodules associated with opportunistic and HIV-related lesions are frequently found in the brains of AIDS patients. However, in many cases, the causative agent is only presumptively suspected. We reviewed 199 brains of AIDS patients with micronodular lesions to clarify their etiology by immunohistochemistry (to Toxoplasma gondii, cytomegalovirus, herpes simplex virus I/II, varicella zoster virus and HIV-p24 core protein), PCR (for herpetic viruses and Mycobacterium tuberculosis) and electron microscopy. Productive HIV infection was observed in 110 cases (55.1%): 30 cases with Toxoplasma gondii encephalitis, 30 with cytomegalovirus encephalitis, eight with multiple cerebral diseases, while in the remaining 42 cases HIV was the only pathogenetic agent. Multinucleated giant cells (hallmark of HIV infection) were found in the MGNs of 85/110 cases with HIV-related lesions; the remaining 25 cases had only p24 positive cells but no multinucleated giant cells. In these latter cases the micronodular lesions had been initially attributed to the main opportunistic agent found in the brain, or defined as subacute encephalitis. Individual microglial nodules positive for an opportunistic pathogen were generally negative for HIV antigens. In 13 cases no opportunistic agent or HIV productive infection was found. In these cases, PCR and electron microscopy examination for HIV and other viral infections were negative. Our data suggest that HIV-immunohistochemistry should be used for the etiological diagnosis of micronodular lesions in AIDS brains, even in the presence of other pathogens. After extensive search, the etiology of the microglial nodules remains unknown in only a small percentage of cases.


New Pulmonary Valvuloplasty Technique by Use of an Hourglass-Shaped Balloon in 3 Adults with Severe Pulmonary Valve Stenosis.
Percutaneous balloon pulmonary valvuloplasty is the preferred therapy for pulmonary valve stenosis. However, the designs of the cylindrical balloons historically used for valvuloplasty have limitations, especially in patients who have large pulmonary annular diameters. The hourglass-shaped V8 Aortic Valvuloplasty Balloon may prove to be an effective alternative. The balloon has 2 large bulbous segments that are separated by a narrowed waist. The geometric shape is maintained throughout inflation, improving fixation and enabling broader leaflet opening. We present our first experience with the V8 balloon in 3 adults who had severe, symptomatic pulmonary valve stenosis. In addition to describing their cases, we detail our sizing technique for pulmonary valvuloplasty with the V8 balloon. Our successful results suggest that the V8 balloon is efficient and safe for balloon pulmonary valvuloplasty in adults with severe pulmonary valve stenosis.


MAP kinases may mediate regulation of the cell cycle in rice by E2F2 phosphorylation.
E2F is the key transcription factor that determines the proliferative status of cells by regulating the G1/S phase of the cell cycle. In this study, we show that in rice (Oryza sativa), OsE2F2 is a phosphorylation target of MAP kinases. The MAP kinases OsMPK3, OsMPK4, and OsMPK6 interact with and phosphorylate OsE2F2. Next, we determined the serine and threonine residues that could play a role in the phosphorylation of OsE2F2. Subsequently, our study suggests a possible link between MAP kinase-mediated OsE2F2 phosphorylation and its impact on DNA proliferation in the roots of rice seedlings. Finally, we found positive feedback regulation of OsMPK4 by OsE2F2. Therefore, our study hints at the potential impact of MAP kinase signaling on the cell cycle of rice plants.


Post-Outbreak Investigation of Pseudomonas aeruginosa Faucet Contamination by Quantitative Polymerase Chain Reaction and Environmental Factors Affecting Positivity.
To perform a post-outbreak prospective study of the Pseudomonas aeruginosa contamination at the faucets (water, aerator and drain) by culture and quantitative polymerase chain reaction (qPCR) and to assess environmental factors influencing occurrence A 450-bed pediatric university hospital in Montreal, Canada Water, aerator swab, and drain swab samples were collected from faucets and analyzed by culture and qPCR for the post-outbreak investigation. Water microbial and physicochemical parameters were measured, and a detailed characterization of the sink environmental and design parameters was performed. The outbreak genotyping investigation identified drains and aerators as the source of infection. The implementation of corrective measures was effective, but post-outbreak sampling using qPCR revealed 50% positivity for P. aeruginosa remaining in the water compared with 7% by culture. P. aeruginosa was recovered in the water, the aerator, and the drain in 21% of sinks. Drain alignment vs the faucet and water microbial quality were significant factors associated with water positivity, whereas P. aeruginosa load in the water was an average of 2 log higher for faucets with a positive aerator. P. aeruginosa contamination in various components of sink environments was still detected several years after the resolution of an outbreak in a pediatric university hospital. Although contamination is often not detectable in water samples by culture, P. aeruginosa is present and can recover its culturability under favorable conditions. The importance of having clear maintenance protocols for water systems, including the drainage components, is highlighted.


AMPA receptor regulation during synaptic plasticity in hippocampus and neocortex.
Discovery of long-term potentiation (LTP) in the dentate gyrus of the rabbit hippocampus by Bliss and Lømo opened up a whole new field to study activity-dependent long-term synaptic modifications in the brain. Since then hippocampal synapses have been a key model system to study the mechanisms of different forms of synaptic plasticity. At least for the postsynaptic forms of LTP and long-term depression (LTD), regulation of AMPA receptors (AMPARs) has emerged as a key mechanism. While many of the synaptic plasticity mechanisms uncovered in at the hippocampal synapses apply to synapses across diverse brain regions, there are differences in the mechanisms that often reveal the specific functional requirements of the brain area under study. Here we will review AMPAR regulation underlying synaptic plasticity in hippocampus and neocortex. The main focus of this review will be placed on postsynaptic forms of synaptic plasticity that impinge on the regulation of AMPARs using hippocampal CA1 and primary sensory cortices as examples. And through the comparison, we will highlight the key similarities and functional differences between the two synapses.


Prevention of carbon tetrachloride (CCl4)-induced toxicity in testes of rats treated with Physalis peruviana L. fruit.
Treatment of rats with carbon tetrachloride (CCl4; 2 ml/kg body weight) once a week for 12 weeks caused a significant decrease in serum levels of testosterone, luteinizing hormone, and follicle-stimulating hormone. These decreases in sex hormones were reduced with Physalis peruviana L. (Cape gooseberry) juice supplementation. In addition, testicular activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase suppressed with CCl4 were elevated after P. peruviana juice supplements. P. peruviana juice supplementation significantly increased the testicular glutathione and significantly decreased the level of lipid peroxidation and the nitric oxide production compared with the CCl4 group. In addition, the decline in the activity of antioxidant enzymes after CCl4 was ameliorated by P. peruviana Moreover, degeneration of germ and Leydig cells along with deformities in spermatogenesis induced after CCl4 injections were prevented with the supplementation of P. peruviana juice. Furthermore, P. peruviana juice attenuated CCl4-induced apoptosis in testes tissue by inhibition of caspase-3 activity. The results clearly demonstrate that P. peruviana juice augments the antioxidants defense mechanism against CCl4-induced reproductive toxicity and provides evidence that the juice may have a therapeutic role in free radical-mediated diseases and infertility.


Daily and seasonal adaptation of the circadian clock requires plasticity of the SCN neuronal network.
Circadian rhythms are an essential property of many living organisms, and arise from an internal pacemaker, or clock. In mammals, this clock resides in the suprachiasmatic nucleus (SCN) of the hypothalamus, and generates an intrinsic circadian rhythm that is transmitted to other parts of the CNS. We will review the evidence that basic adaptive functions of the circadian system rely on functional plasticity in the neuronal network organization, and involve a change in phase relation among oscillatory neurons. We will illustrate this for: (i) photic entrainment of the circadian clock to the light-dark cycle; and (ii) seasonal adaptation of the clock to changes in day length. Molecular studies have shown plasticity in the phase relation between the ventral and dorsal SCN during adjustment to a shifted environmental cycle. Seasonal adaptation relies predominantly on plasticity in the phase relation between the rostral and caudal SCN. Electrical activity is integrated in the SCN, and appears to reflect the sum of the differently phased molecular expression patterns. While both photic entrainment and seasonal adaptation arise from a redistribution of SCN oscillatory activity patterns, different neuronal coupling mechanisms are employed, which are reviewed in the present paper.


Chronic infectious mononucleosis syndrome, pancytopenia, and polyclonal B-lymphoproliferation terminating in acute lymphoblastic leukemia.
A 17-year-old previously healthy girl is reported who developed acute infectious mononucleosis followed by progressive ill health over 20 months, associated with pancytopenia and a polyclonal B-lymphoproliferation, terminating in acute lymphoblastic leukemia (ALL). Epstein-Barr virus (EBV) was recovered from the patient's nasopharyngeal secretions; serologic titers of antibodies to EBV-associated antigens were compatible with a chronic persistent EBV infection. Plasma interferon levels were markedly elevated. EBV-specific cell-mediated immunity, as well as Natural killer (NK) cell activity were markedly deficient. Other studies of cell-mediated immunity revealed notable abnormalities, including abnormalities in T-cell subset ratios, and a serum blocker of autologous mitogen-induced lymphoproliferation. Humoral (plasma)-mediated, but not cell-mediated, suppression of hemopoiesis was demonstrated using in vitro erythroid and myeloid colony culture techniques. Immunophenotyping of the patient's bone marrow cells preterminally was consistent with ALL. Autopsy revealed pathologic changes of ALL in marrow and multiple organs. We conclude that our patient developed an EBV-driven lymphoproliferative disorder, with associated defective cell-mediated immunity and hemopoiesis. Ultimately, the patient's documented polyclonal lymphoproliferative state was superimposed by acute lymphoblastic leukemia.


Care with prejudice.
A nurse-led initiative in South Africa is bringing palliative care to the country's prisoners. Supported by the Diana, Princess of Wales Fund, the initiative means prisoners who would previously have died without any support will now receive pain control, help with daily tasks and companionship.


Effects of chronic expression of the HIV-induced protein, transactivator of transcription, on circadian activity rhythms in mice, with or without morphine.
Patients with human immunodeficiency virus (HIV) infection exhibit changes in sleep patterns, motor disorders, and cognitive dysfunction; these symptoms may be secondary to circadian rhythm abnormalities. Studies in mice have shown that intracerebral injection of an HIV protein, transactivator of transcription (Tat), alters the timing of circadian rhythms in a manner similar to light. Therefore, we tested the hypothesis that chronic Tat expression alters circadian rhythms, especially their entrainment to a light-dark (LD) cycle, by using transgenic mice in which Tat expression in the brain was induced via a doxycycline (DOX)-sensitive, glial fibrillary-associated, protein-restricted promoter. Because opiate substance abuse, which shares comorbidity with HIV infection, also disrupts sleep, a final experiment assessed the effects of morphine exposure on circadian rhythms in wild-type and Tat transgenic mice. Mice housed in cages equipped with running wheels were fed chow with or without DOX. Experiment 1 revealed a small but significant (P < 0.05) difference between groups in the phase angle of entrainment and a 15% decrease in the wheel running in the DOX group (P < 0.005). During exposure to constant darkness, DOX did not alter the endogenous period length of the circadian rhythm. Experiment 2 investigated the effect of DOX on circadian rhythms in wild-type and Tat(+) mice during exposure to a normal or phase-shifted LD cycle, or morphine treatment without any change in the LD cycle. Tat induction significantly decreased wheel running but did not affect entrainment to the normal or shifted LD cycle. Morphine decreased wheel running without altering the phase angle of entrainment, and the drug's effects were independent of Tat induction. In conclusion, these findings suggest that chronic brain expression of Tat decreases locomotor activity and the amplitude of circadian rhythms, but does not affect photic entrainment or reentrainment of the murine circadian pacemaker.


Gender bias in colorectal surgery fellowship letters of recommendation.
As leaders strive to create equitable surgical pipelines, one process under scrutiny is letters of recommendation (LORs). We sought to review the Colon and Rectal Surgery (CRS) Resident Candidate Assessment questionnaire and LORs for gendered differences. This retrospective observational study of letters of recommendation to CRS fellowship during the 2018-2019 application cycle utilized linguistic Inquiry and Word Count (LIWC2015) software to assess letter length and themes comparing differences by applicant and referee gender. 103 applicants (35 % women) with 363 LORs (16 % written by women) were included. Short answer responses were longer for women applicants, while LORs were longer for men applicants (368 vs 325 words p = 0.03). Men applicants' strengths had more technical skill descriptors, while women applicants' strengths had more emotional language and cognitive and perceptual words. This study found significant differences between LORs written for CRS fellowship applicants based on gender.


The potential anticoagulant property of Caulerpa lentillifera crude extract.
Anticoagulants have been used in the treatment of several circulatory diseases and thrombotic disorders, and in the blood sampling for hematologic analysis. Sulfated polysaccharides (SP), which have anticoagulant properties, are found in most seaweeds, including Caulerpa spp. The study generally aimed to evaluate the potential anticoagulant property of Caulerpa lentillifera. The whole plant of fresh C. lentillifera was washed thoroughly with distilled water and manually expressed to obtain the extract. C. lentillifera extract was tested in two phases. Phase one utilized nine male albino rabbits, which were randomly and equally allocated into three groups: (1) negative control (oral distilled water and subsequent in vitro mixing of extracted blood with normal saline solution), (2) positive control (oral aspirin and subsequent in vitro mixing of extracted blood with normal saline solution), and (3) experimental group (oral distilled water and in vitro mixing of extracted blood with C. lentillifera extract). Blood coagulation was evaluated by measuring the clotting time using the slide and tube methods. In phase two, peripheral blood from three apparently healthy adult dogs were used. Blood collection was performed thrice. In each collection, the sample was divided into five aliquots: (1) negative control (normal saline solution), (2) positive control (ethylenediaminetetraacetic acid [EDTA]), and (3-5) experimental treatments at 0.1, 0.15, and 0.2 ml of C. lentillifera extract. Coagulation was evaluated by measuring the clotting time using the tube method. Phase one results revealed significant differences on the clotting time between the negative and the positive and experimental groups (P < 0.05), and no significant differences on the clotting time between the positive and the experimental groups (P > 0.05). In phase two, all blood samples mixed with EDTA did not clot, while the negative control had an average clotting time of 2.01 min. Blood mixed with 0.2 ml of C. lentillifera extract had the longest coagulation time (15.49 min). Simple linear regression revealed a positive significant correlation (multiple R = 0.9450, R2 = 0.8931, P = 0.02) implying dose-dependent anticoagulant potential. The study showed that C. lentillifera extract may have a potential anticoagulant property due to its component SP.


Precipitation-optimised targeting of nitrogen fertilisers in a model maize cropping system.
Typically, half of the nitrogen (N) fertiliser applied to agricultural fields is lost to the wider environment. This inefficiency is driven by soil processes such as denitrification, volatilisation, surface run-off and leaching. Rainfall plays an important role in regulating these processes, ultimately governing when and where N fertiliser moves in soil and its susceptibility to gaseous loss. The interaction between rainfall, plant N uptake and N losses, however, remains poorly understood. In this study we use numerical modelling to predict the optimal N fertilisation strategy with respect to rainfall patterns and offer mechanistic explanations to the resultant differences in optimal times of fertiliser application. We developed a modelling framework that describes water and N transport in soil over a growing season and assesses nitrogen use efficiency (NUE) of split fertilisations within the context of different rainfall patterns. We used ninety rainfall patterns to determine their impact on optimal N fertilisation times. We considered the effects of root growth, root N uptake, microbial transformation of N and the effect of soil water saturation and flow on N movement in the soil profile. On average, we show that weather-optimised fertilisation strategies could improve crop N uptake by 20% compared to the mean uptake. In drier years, weather-optimising N applications improved the efficiency of crop N recovery by 35%. Further analysis shows that maximum plant N uptake is greatest under drier conditions due to reduced leaching, but it is harder to find the maximum due to low N mobility. The model could capture contrasting trends in NUE seen in previous arable cropping field trials. Furthermore, the model predicted that the variability in NUE seen in the field could be associated with precipitation-driven differences in N leaching and mobility. In conclusion, our results show that NUE in cropping systems could be significantly enhanced by synchronising fertiliser timings with both crop N demand and local weather patterns.


Development and evaluation of new factor scales for the Expectations About Counseling Inventory in a college sample.
Given the lack of agreement over the factor structure and scoring system used with the Expectations About Counseling Inventory (EAC-B), the primary purpose of this investigation was to reevaluate the factor structure of the EAC-B and to construct factor scales based on that structure. After constructing these scales, the second objective was to evaluate the relationships among expectations about counseling, the five-factor model of personality (FFM), and gender-related variables. The responses of 460 undergraduate students to all 66 items on the EAC-B suggested three factors: facilitative conditions, counselor expertise, and client involvement. Expectations for facilitative conditions were positively correlated with extraversion, agreeableness, conscientiousness, masculinity, and femininity; expectations for counselor expertise were negatively correlated with openness and agreeableness and positively correlated with masculinity; and expectations for client involvement were positively correlated with extraversion, openness, agreeableness, conscientiousness, and femininity. Femininity was the strongest predictor of the facilitative conditions and client involvement scales when the effects of all the other variables were partialled out, whereas openness to experience and gender were the best predictors of counselor expertise when the effects of all the other variables were partialled out.


B-type natriuretic peptide as a predictor of declining cognitive function and dementia--a cohort study of an elderly general population with a 5-year follow-up.
Several traditional cardiovascular risk factors assessed in the middle-aged are associated with the risk of dementia, but they are known to lose much of their prognostic value when measured in the elderly. The aim of the study was to compare B-type natriuretic peptide (BNP) with previously known risk markers for dementia in their association with cognitive decline and dementia during a follow-up. A total of 464 subjects free of dementia aged 75 years or more were examined and followed up for 5 years in a prospective population-based stratified cohort study. The association of clinical variables to base-line Mini Mental State Examination score (MMSE), the decline of MMSE, and onset of dementia during the follow-up were examined. The only variable to significantly associate with the decline of MMSE was BNP (beta 0.140; P = 0.019). A total of 59 new cases of dementia were diagnosed after the follow-up. Significant predictors of the occurrence of dementia over the study period were BNP (adjusted odds ratio (OR) 1.53; 95% confidence interval (CI) 1.09-2.16; P = 0.013), length of education (OR 0.50; 95% CI 0.33-0.77; P = 0.001), and diagnosis of hypertension (OR 0.53; 95% CI 0.27-0.95; P = 0.036). BNP remained as a significant predictor of dementia and the decline of MMSE even after adjustment to the base-line MMSE. BNP is an independent harbinger of the cognitive decline and incidence of new onset of dementia in an elderly general population. This is a ground for testing the impact of antihypertensive treatment in the prevention of cognitive impairment in those with elevated BNP.


Undifferentiated febrile illness in Kathmandu, Nepal.
Undifferentiated febrile illnesses (UFIs) are common in low- and middle-income countries. We prospectively investigated the causes of UFIs in 627 patients presenting to a tertiary referral hospital in Kathmandu, Nepal. Patients with microbiologically confirmed enteric fever (218 of 627; 34.8%) randomized to gatifloxacin or ofloxacin treatment were previously reported. We randomly selected 125 of 627 (20%) of these UFI patients, consisting of 96 of 409 (23%) cases with sterile blood cultures and 29 of 218 (13%) cases with enteric fever, for additional diagnostic investigations. We found serological evidence of acute murine typhus in 21 of 125 (17%) patients, with 12 of 21 (57%) patients polymerase chain reaction (PCR)-positive for Rickettsia typhi. Three UFI cases were quantitative PCR-positive for Rickettsia spp., two UFI cases were seropositive for Hantavirus, and one UFI case was seropositive for Q fever. Fever clearance time (FCT) for rickettsial infection was 44.5 hours (interquartile range = 26-66 hours), and there was no difference in FCT between ofloxacin or gatifloxacin. Murine typhus represents an important cause of predominantly urban UFIs in Nepal, and fluoroquinolones seem to be an effective empirical treatment.


Development and tuning of the microwave resonant cavity of a cryogenic cesium atomic fountain clock.
A cryogenic cesium atomic fountain clock is a novel clock with the microwave cavity and atomic free flight region placed in liquid nitrogen. On the one hand, the blackbody radiation shift is reduced at cryogenic temperature. On the other hand, the vacuum in the atomic free flight region is optimized, and the background gas collision shift reduced. The microwave resonant cavity is the most important unit in a cryogenic cesium atomic fountain clock. Through theoretical and simulative investigation, this study designs the configuration and dimensions for an optimized microwave cavity. Concurrently, experiments reveal the effects of temperature, pressure, humidity, and other factors on the resonant frequency of the microwave cavity. Combining the theoretical and experimental study, we obtain the resonant frequency difference between the microwave cavity in a cryogenic vacuum and at room temperature and ambient pressure. By subtracting this frequency difference, we adjust the microwave cavity for room temperature and ambient pressure, then vacuumize and immerse it in liquid nitrogen for verification and fine tuning. Finally, we determine that the microwave cavity resonant frequency deviation from the clock transition frequency is 10 kHz with an unloaded quality factor of 25 000, which meets the application requirements of the cryogenic cesium atomic fountain clock.


The psychoneuroimmunology of depression.
Chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal (HPA) axis and the immune system, acts as a trigger for anxiety and depression. There is experimental and clinical evidence that the rise in the concentration of pro-inflammatory cytokines and glucocorticoids, which occurs in a chronically stressful situation and also in depression, contribute to the behavioural changes associated with depression. A defect in serotonergic function is associated with these hormonal and immune changes. Neurodegenerative changes in the hippocampus, prefrontal cortex and amygdalae are the frequent outcome of the changes in the HPA axis and the immune system. Such changes may provide evidence for the link between chronic depression and dementia in later life.


Group Health Cooperative's community services initiative.
Service to the broader community is an important component of Group Health Cooperative's (GHC's) tradition, values, and mission. The role and potential of community services in a staff model HMO requires consensus, careful planning and communication, and attention to results. This paper describes GHC's efforts to define, implement, and sustain its community services initiative.


Increased misophonia in self-reported Autonomous Sensory Meridian Response.
Autonomous Sensory Meridian Response (ASMR) is a sensory experience elicited by auditory and visual triggers, which so far received little attention from the scientific community. This self-reported phenomenon is described as a relaxing tingling sensation, which typically originates on scalp and spreads through a person's body. Recently it has been suggested that ASMR shares common characteristics with another underreported condition known as misophonia, where sounds trigger negative physiological, emotional and behavioural responses. The purpose of this study was to elucidate whether ASMR is associated with heightened levels of misophonia. The Misophonia Questionnaire (MQ) was administered to individuals reporting to experience ASMR and to age and gender matched controls. Compared to controls ASMR group scored higher on all subscales of MQ including the Misophonia Symptom Scale, the Misophonia Emotions and Behaviors Scale and the Misophonia Severity Scale. Individuals reporting ASMR experience have elevated levels of misophonia.


[Experienced anesthetists show better reaction to central gas supply dropout--an anesthesia simulator study].
The loss of pipeline pressure in a central gas supply system is a rare but potentially hazardous complication in anaesthesia and critical care. In an anaesthesia simulator study, reactions of 20 anaesthetists to this simulated critical incident were monitored and evaluated. A comparison between novice (n = 10) and experienced anaesthesia residents/consultants (n = 10) determined a significantly quicker and more on-target reaction by the experienced anaesthetists. Unlike older cycle system anaesthesia machines, update anaesthesia ventilators (CICERO EM, Dräger, Lübeck) do not permit manual ventilation of a patient in a "closed-system" once pipeline pressure drops to zero. In this highly hazardous event, the patient has to be ventilated by reservoir bag until a sufficient back-up system delivering high inspiratory oxygen concentrations can be installed, because he is otherwise prone to diffusion hypoxia. Installation of mandatory (anaesthesia-machine integrated) back-up systems for respirators without cycle systems would therefore increase patient safety. A general algorithm for loss of pipeline pressure can be described only after a back-up system has been installed.


Tissue Doppler echocardiography.
Tissue Doppler echocardiography, since its introduction more than 2 decades ago, had revolutionized echocardiography. In the quest to directly quantify myocardial function, increase sensitivity to detect early subtle myocardial dysfunction and improve ease of use, tissue Doppler echocardiography has evolved from pulsed wave tissue Doppler, to color-coded tissue Doppler and to 2-dimensional (2D) speckle tracking, and from myocardial velocity to strain/strain rate imaging. Over the years, numerous studies have demonstrated the value of tissue Doppler echocardiography in the diagnosis and risk stratification of a wide range of cardiac diseases. However, each generational change in tissue Doppler echocardiography involves technological software advancements that are not directly comparable to previous generations. To extensively present the technical differences between tissue Doppler imaging and speckle tracking analyses, and to review the clinical implications of myocardial velocity, strain and strain rate imaging by tissue Doppler versus speckle tracking, is well beyond the scope of the present article. Thus, the aim of the present review is to focus on tissue Doppler imaging, from basic physical principles and technical limitations, to differences in myocardial velocity, strain and strain rate imaging in healthy and diseased states, and finally the prognostic value of tissue Doppler deformation imaging in predicting adverse cardiac outcomes.


The health economics of palliative care.
Only a few studies have assessed the economic outcomes of palliative therapy. The major areas of interest include hospice care, the process and structure of care, symptom management, and palliative chemotherapy compared to best supportive care. Compared with nonhospice care, hospice care saves at best 3% of total care costs. Advance directives done early in the disease course may save end-of-life care costs, but when done in the hospital do not save money or influence care choices. Nurse coordination of palliative care maintained clinical outcomes of dying patients and saved 40% of costs. A structured ethics review of those likely to die in the intensive care unit also appears to match the type of care to the outcome, and save costs. There are remarkably few randomized clinical trials of pain and symptom control interventions in end-of-life care, so few conclusions can be drawn about current treatments. There are no examples of chemotherapy that save money compared to best supportive care. Current data suggest that changes in palliative care cost can only come from dramatic changes in how we provide care. One model is coordinated, expert, high-volume care that can prevent end-of-life hospitalization, with early use of advance directives. Preliminary data from our program support the hypothesis that costs may be reduced by 40% to 70%.


Relationship between hepcidin and ferritin in haemodialysed patients.
Hepcidin is a key regulator of iron metabolism. It binds to ferroportin and causes the trapping of iron in cells, rendering it unavailable for erythropoiesis. The synthesis of hepcidin is upregulated by high iron stores and inflammation. Haemodialysed patients suffer from anaemia and impaired iron management, the cause of which is multifactorial. Our aim was to describe the relationship between hepcidin and other parameters of iron metabolism, erythropoiesis, and inflammation. Complete blood cell counts, hepcidin, parameters of iron metabolism, and inflammation were measured in samples from 164 dialysed patients and 37 control healthy volunteers. Patients were subdivided according to the time of dialysis session. According to the time of haemodialysis, iron levels showed an insignificant tendency for diurnal variability, whereas hepcidin levels were markedly different. Non-parametric correlations showed a weak, but statistically significant correlation between parameters of iron metabolism and inflammation in the entire group of patients. No correlation was found between hepcidin and other biochemical parameters in controls. Non-parametric correlations were also performed in the time subgroups of patients. It seems that the influence of inflammation on hepcidin levels in haemodialysed patients is not crucial and other factors (e.g. hepcidin retention) are involved.


SPECT-CT for topographic mapping of sentinel lymph nodes prior to gamma probe-guided biopsy in head and neck squamous cell carcinoma.
Lymphoscintigraphic planar imaging is a common procedure for sentinel lymph node imaging prior to lymph node biopsy, but fails to elucidate the specific lymphatic drainage. Composite functional/anatomical imaging (SPECT-CT) has the potential to enhance topographic orientation and diagnostic sensitivity of sentinel lymph node imaging, but has not yet been applied in the head and neck region. A total of 30 patients were investigated. Planar imaging was 5 min, 265 x 265, right and left lateral; 500 kilocounts (Kcts) and SPECT (GE Millenium VG Hawk Eye 6 degrees/30s. step, 128 x 128, slice thickness 4.42 mm). Scans were performed 60 min after intra-mucodermal injection of 0.1 ml of 20 MBq 99mTc nanocolloid in patients with squamous cell cancer of the head and neck. SPECT studies were analysed by filtered back projection (FBP: Hann (0.7) prefiltering, Butterworth (0.5) postfiltering) and reconstruction (OSEM: Post Filter Hamming (0.85), 2 Iterations) and independently viewed with the co-registered CT image (eNTEGRA Functional Anatomical Fusion Vers 2.0216). The results were validated by comparing the results of each method employed in all 30 cases and intraoperative gamma probe-guided sentinel lymph node biopsy with histological examination in 13 of these patients. The majority of patients had more than one sentinel node (mean 1.63, min. 0, max. 4). Seven out of the 30 studies demonstrated lymphatic flow to the contralateral side of the neck. Forty-nine sentinel nodes were identified by iteratively reconstructed SPECT-CT. Thirty-eight out of these 49 could be located in lymphoscintigraphic planar imaging, whereas only 24/49 were detected in filtered back projection, respectively. In 11 of the 30 cases, a clinically unpredictable pattern of lymphatic drainage was observed. No correlation was found between T stage or tumour location and the number of sentinel nodes detected. In one out of the 13 cases, in whom imaging was followed by intraoperative gamma probe-guided biopsy, no sentinel node could be detected with the probe in the proximity of the primary tumour, although the node was clearly discernible in the reconstructed SPECT-CT. Composite functional/anatomical imaging (SPECT-CT) is feasible for sentinel lymph node detection. It enhances topographic orientation and diagnostic sensitivity with more sentinel nodes being detectable than by planar lymphoscintigraphy alone. Planar imaging should be accompanied by iterative reconstructed SPECT-CT to identify lymph nodes adjacent to the primary lesion. Such nodes are easily overlooked by planar lymphoscintigraphy and intraoperative gamma probes, as the high activity at the injection site can obscure their detection.


Barriers to the treatment of adolescent type 2 diabetes--a survey of provider perceptions.
Type 2 diabetes mellitus (T2DM) is increasingly common among children and adolescents. However, achievement of good metabolic control has been difficult in this population. The aim of this study was to survey pediatric endocrine and diabetes specialists regarding the issues they consider to be barriers to successful treatment of adolescent T2DM. An electronic questionnaire was administered to 220 physicians and nurses attending a conference on pediatric diabetology in 2001. The issues that were most strongly perceived as barriers to successful treatment of adolescents with T2DM were prevalence of high-risk lifestyle in other family members (98%), lack of immediate risk to life reducing patient motivation (89%), lack of guidelines regarding optimal treatment (73%), prevalence of behavioral and/or psychiatric disorders (71%), and cultural/language barriers (65%). The survey also revealed that in the majority of clinics, T2DM education programs were not designed specifically for type 2 patients nor delivered by a specifically trained education team. Furthermore, despite the fact that cultural and ethnic differences were identified as important barries to care, educational materials designed for particular racial and cultural groups were used in only 37% of the clinics. This survey identifies a number of areas perceived by clinicians to be significant barriers to successful treatment of T2DM in adolescent patients. Given the multiple challenges identified by the survey, programs addressed specifically to the characteristics of adolescents with T2DM will be necessary, including materials appropriate to the developmental stage and ethnic background of patients.


Learning history and cholinergic modulation in the dorsal hippocampus are necessary for rats to infer the status of a hidden event.
Identifying statistical patterns between environmental stimuli enables organisms to respond adaptively when cues are later observed. However, stimuli are often obscured from detection, necessitating behavior under conditions of ambiguity. Considerable evidence indicates decisions under ambiguity rely on inference processes that draw on past experiences to generate predictions under novel conditions. Despite the high demand for this process and the observation that it deteriorates disproportionately with age, the underlying mechanisms remain unknown. We developed a rodent model of decision-making during ambiguity to examine features of experience that contribute to inference. Rats learned either a simple (positive patterning) or complex (negative patterning) instrumental discrimination between the illumination of one or two lights. During test, only one light was lit while the other relevant light was blocked from physical detection (covered by an opaque shield, rendering its status ambiguous). We found experience with the complex negative patterning discrimination was necessary for rats to behave sensitively to the ambiguous test situation. These rats behaved as if they inferred the presence of the hidden light, responding differently than when the light was explicitly absent (uncovered and unlit). Differential expression profiles of the immediate early gene cFos indicated hippocampal involvement in the inference process while localized microinfusions of the muscarinic antagonist, scopolamine, into the dorsal hippocampus caused rats to behave as if only one light was present. That is, blocking cholinergic modulation prevented the rat from inferring the presence of the hidden light. Collectively, these results suggest cholinergic modulation mediates recruitment of hippocampal processes related to past experiences and transfer of these processes to make decisions during ambiguous situations. Our results correspond with correlations observed between human brain function and inference abilities, suggesting our experiments may inform interventions to alleviate or prevent cognitive dysfunction. © 2015 Wiley Periodicals, Inc.


The enhanced electrocatalytic performance of nanoscopic Cu6Pd12Fe12 heterometallic molecular box encaged cytochrome c.
Designing molecular cages for atomic/molecular scale guests is a special art used by material chemists to harvest the virtues of the otherwise vile idea known as "the cage". In recent years, there has been a notable surge in research investigations focused on the exploration and utilization of the distinct advantages offered by this art in the advancement of efficient and stable bio-electrocatalysts. This usually is achieved through encapsulation of biologically accessible redox proteins within specifically designed molecular cages and matrices. Herein, we present the first successful method for encaging cytochrome c (Cyt-c), a clinically significant enzyme system, inside coordination-driven self-assembled Cu6Pd12Fe12 heterometallic hexagonal molecular boxes (Cu-HMHMB), in order to create a Cyt-c@Cu-HMHMB composite. 1H NMR, FTIR, and UV-Vis spectroscopy, ICP-MS, TGA and voltammetric investigations carried out on the so-crafted Cyt-c@Cu-HMHMB bio-inorganic composite imply that the presented strategy ensures encaging of Cyt-c in a catalytically active, electrochemically stable and redox-accessible state inside the Cu-HMHMB. Cyt-c@Cu-HMHMB is demonstrated to exhibit excellent stability and electrocatalytic activity toward very selective, sensitive electrochemical sensing of nitrite exhibiting a limit of detection as low as 32 nanomolar and a sensitivity of 7.28 μA μM-1 cm-2. Importantly, Cyt-c@Cu-HMHMB is demonstrated to exhibit an excellent electrocatalytic performance toward the 4ē pathway oxygen reduction reaction (ORR) with an onset potential of 0.322 V (vs. RHE) and a Tafel slope of 266 mV dec-1. Our findings demonstrate that Cu-HMHMB is an excellent matrix for Cyt-c encapsulation. We anticipate that the entrapment-based technique described here will be applicable to other enzyme systems and Cyt-c for various electrochemical and other applications.