HIV antibody screening of blood donations in the United Kingdom.
Routine screening of blood donations for anti-HIV commenced in the UK during October 1985 and by the end of February 1987 approximately 3.7 million donations had been tested. Seventy-two were confirmed anti-HIV positive, i.e. 0.002%. Of the anti-HIV-positive donors interviewed to date, the majority are young homosexual or bisexual men or intravenous drug abusers. Included in the study are data collected on approximately 470,000 donors giving blood for the first time. Twenty of these have been confirmed anti-HIV positive (0.004%), and 19 interviewed have admitted to being in risk categories. In 5 instances a positive anti-HIV donor was found negative on a previous occasion, and in 1 instance the products from the donation led to seroconversion in the recipients. The majority of anti-HIV-positive donors attending for blood donation did so because they did not consider that the self-exclusion categories specified in the leaflet issued to donors applied to them since homosexual activity or drug abuse was not currently being practised.


Dietary Intake and Milk Micronutrient Levels in Lactating Women with Full and Partial Breastfeeding.
Micronutrient intake and status in lactating women may impact micronutrient levels in milk. This study aimed to determine the micronutrient intake and status in lactating women, and their association with micronutrient levels in human milk. Lactating women were enrolled at 4-6 months postpartum. A 24h food recall was examined and nutrient intakes were analyzed using INMUCAL software. Human milk samples were collected to analyze calcium, copper, iron, and zinc levels. Plasma zinc and serum ferritin levels were determined. Thirty-four women participated; 19 were classified as full breastfeeding and 15 as partial breastfeeding. Mean levels of calcium, copper, iron, and zinc in human milk were 243, 0.2, 0.2, and 1.56 mg/L, respectively. The prevalence of zinc deficiency (plasma zinc < 10.7 µmol/L) was 11.8%. No lactating women had iron deficiency. Nutrient intakes were lower than the recommended amounts in 38%-70% of participants, and were not correlated with corresponding nutrient levels in human milk. Multiple linear regression showed significant association between zinc levels in human milk and plasma for lactating women with full breastfeeding (β = 0.034, 95% confidence interval [0.003, 0.067], p = 0.040). Lactating women were at risk of micronutrient deficiency. There was an association between zinc levels in human milk and plasma of lactating women with full breastfeeding. As the nutritional status of lactating women influences the quality of human milk, we should encourage good nutrient intake for lactating women.


Comparing the effect of positioning on cerebral autoregulation during radical prostatectomy: a prospective observational study.
Surgery in the prolonged extreme Trendelenburg position may lead to elevated intracranial pressure and compromise cerebral hemodynamic regulation. We hypothesized that robot-assisted radical prostatectomy with head-down tilt causes impairment of cerebral autoregulation compared with open retropubic radical prostatectomy in the supine position. Patients scheduled for elective radical prostatectomy were included at a tertiary care prostate cancer clinic. Continuous monitoring of the cerebral autoregulation was performed using the correlation method. Based on measurements of cerebral oxygenation with near-infrared spectroscopy and invasive mean arterial blood pressure (MAP), a moving correlation coefficient was calculated to obtain the cerebral oxygenation index as an indicator of cerebral autoregulation. Cerebral autoregulation was measured continuously from induction until recovery from anesthesia. There was no significant difference in cerebral autoregulation between robot-assisted and open retropubic radical prostatectomy during induction (p = 0.089), intraoperatively (p = 0.162), and during recovery from anesthesia (p = 0.620). Age (B = 0.311 [95% CI 0.039; 0.583], p = 0.025) and a higher difference between baseline MAP and intraoperative MAP (B = 0.200 [95% CI 0.073; 0.327], p = 0.002) were associated with impaired cerebral autoregulation, whereas surgical technique was not (B = 3.339 [95% CI 1.275; 7.952], p = 0.155). Compared with open radical prostatectomy in the supine position, robot-assisted surgery in the extreme Trendelenburg position with capnoperitoneum did not lead to an impairment of cerebral autoregulation during the perioperative period in our study population. DRKS00010014, date of registration: 21.03.2016, retrospectively registered.


The bedside examination in dysphagia.
The evaluation of swallowing disorders currently uses a variety of methods. The most common dichotomy is between instrumental and noninstrumental or clinical examinations. The clinical bedside assessment often is considered the mainstay of dysphagia management. As the first line of assessment, it frequently defines the process and requisites of the task. This article reviews the available methods of noninstrumental bedside swallowing assessment and considers the issues surrounding the use of these approaches today.


Consequences of starting whole cow milk at 6 months of age.
Two groups of infants, one fed whole cow milk commencing at 6 months of age (n = 69) and the other continuing to receive iron-fortified infant formula (n = 98), were closely observed over their second 6 months of life. At 12 months of age, infants fed cow milk had significantly lower mean serum ferritin levels and mean corpuscular volume, higher free erythrocyte protoporphyrin values, and greater incidence of hemoglobin values less than 11 g/dl than did formula-fed infants. There were no significant differences in frequency of otitis media, wheezing episodes, nasal discharge or congestion, diaper dermatitis, constipation, guaiac-positive stools, or hospital admissions between the two groups. These data suggest that, to avoid iron deficiency, infants should continue to receive iron-fortified formula throughout the first year of life or a daily iron supplement if they are fed whole cow milk before their first birthday.


Patch-based models and algorithms for image processing: a review of the basic principles and methods, and their application in computed tomography.
Image models are central to all image processing tasks. The great advancements in digital image processing would not have been made possible without powerful models which, themselves, have evolved over time. In the past decade, "patch-based" models have emerged as one of the most effective models for natural images. Patch-based methods have outperformed other competing methods in many image processing tasks. These developments have come at a time when greater availability of powerful computational resources and growing concerns over the health risks of the ionizing radiation encourage research on image processing algorithms for computed tomography (CT). The goal of this paper is to explain the principles of patch-based methods and to review some of their recent applications in CT. We first review the central concepts in patch-based image processing and explain some of the state-of-the-art algorithms, with a focus on aspects that are more relevant to CT. Then, we review some of the recent application of patch-based methods in CT. Patch-based methods have already transformed the field of image processing, leading to state-of-the-art results in many applications. More recently, several studies have proposed patch-based algorithms for various image processing tasks in CT, from denoising and restoration to iterative reconstruction. Although these studies have reported good results, the true potential of patch-based methods for CT has not been yet appreciated. Patch-based methods can play a central role in image reconstruction and processing for CT. They have the potential to lead to substantial improvements in the current state of the art.


Medical image fusion based on hybrid three-layer decomposition model and nuclear norm.
The aim of medical image fusion technology is to synthesize multiple-image information to assist doctors in making scientific decisions. Existing studies have focused on preserving image details while avoiding halo artifacts and color distortions. This paper proposes a novel medical image fusion algorithm based on this research objective. First, the input image is decomposed into structure, texture, and local mean brightness layers using a hybrid three-layer decomposition model that can fully extract the features of the original images without the introduction of artifacts. Secondly, the nuclear norm of the patches, which are obtained using a sliding window, are calculated to construct the weight maps of the structure and texture layers. The weight map of the local mean brightness layer is constructed by calculating the local energy. Finally, remapping functions are applied to enhance each fusion layer, which reconstructs the final fusion image with the inverse operation of decomposition. Subjective and objective experiments confirm that the proposed algorithm has a distinct advantage compared with other state-of-the-art algorithms.


Transcriptomic and proteomic analyses reveal the first occurrence of diverse toxin groups in Millepora alcicornis.
Millepora alcicornis is a reef-forming cnidarian widely distributed in the Mexican Caribbean. Millepora species or "fire corals" inflict a painful stinging reaction in humans when touched. Even though hundreds of organic and polypeptide toxins have been characterized from sea anemones and jellyfish, there are few reports regarding the diversity of toxins synthesized by fire corals. Here, based on transcriptomic analysis of M. alcicornis, several predicted proteins that show amino acid sequence similarity to toxins were identified, including neurotoxins, metalloproteases, hemostasis-impairing toxins, serin proteases, cysteine-rich venom proteins, phospholipases, complement system-impairing toxins, phosphodiesterases, pore-forming toxins, and L-aminoacid oxidases. The soluble nematocyst proteome of this organism was shown to induce hemolytic, proteolytic, and phospholipase A2 effects by gel zymography. Protein bands or spots on 1D- and 2D-PAGE gels corresponding to zones of hemolytic and enzymatic activities were excised, subjected to in-gel digestion with trypsin, and analyzed by mass spectrometry. These proteins exhibited sequence homology to PLA2s, metalloproteinases, pore-forming toxins, and neurotoxins, such as actitoxins and CrTX-A. The complex array of venom-related transcripts that were identified in M. alcicornis, some of which are first reported in "fire corals", provide novel insight into the structural richness of Cnidarian toxins and their distribution among species. SIGNIFICANCE: Marine organisms are a promising source of bioactive compounds with valuable contributions in diverse fields such as human health, pharmaceuticals, and industrial application. Currently, not much attention has been paid to the study of fire corals, which possess a variety of molecules that exhibit diverse toxic effects and therefore have great pharmaceutical and biotechnological potential. The isolation and identification of novel marine-derived toxins by classical approaches are time-consuming and have low yields. Thus, next-generation strategies, like base-'omics technologies, are essential for the high-throughput characterization of venom compounds such as those synthesized by fire corals. This study moves the field forward because it provides new insights regarding the first occurrence of diverse toxin groups in Millepora alcicornis. The findings presented here will contribute to the current understanding of the mechanisms of action of Millepora toxins. This research also reveals important information related to the potential role of toxins in the defense and capture of prey mechanisms and for designing appropriate treatments for fire coral envenomation. Moreover, due to the lack of information on the taxonomic identification of Millepora, the insights presented here can advise the taxonomic classification of the species of this genus.


Time trends in demand for family planning satisfied: analysis of 73 countries using national health surveys over a 24-year period.
Universal access to family planning is key to extend its health and economic benefits worldwide. Our aim was to track progress in demand for family planning satisfied with modern methods (mDFPS) and its inequalities in low- and middle-income countries (LMICs). Analyses were based on Demographic and Health Surveys and Multiple Indicator Cluster Surveys carried out between 1993 and 2017 in 73 LMICs, using data for married women aged 15-49 years. We estimated trends in mDFPS coverage by country and world region and evaluated trends in wealth-based inequalities. The analyses pooling all countries together were stratified by wealth quintiles, area of residence and woman's age. mDFPS coverage in 2030 for each country was predicted using a linear model. Overall, mDFPS increased and poor-rich gaps narrowed. Eastern & Southern Africa showed an average increase of 1.5 percentage points (p.p.) a year, being the region with the fastest progress. West & Central Africa had an increase in mDFPS of 1 p.p. a year but current coverage is still below 40%. Generally, inequalities were reduced, except for West & Central Africa and Europe & Central Asia where almost no change was observed. The country with the fastest progress in mDFPS was Rwanda, with an increase of 5 p.p./y, while Timor Leste had the fastest reduction in absolute inequality, less 3.8 p.p./y. Inequalities by area of residence were reduced, but large gaps remain. A similar trend was observed for different age groups. If the current trend is not accelerated, 44 countries will not achieve universal coverage in mDFPS by 2030. Generally, mDFPS is increasing and inequalities are decreasing. However, progress is slow in some regions, especially West & Central Africa, where low coverage is combined with high levels of inequalities. Efforts to increase family planning coverage must be prioritized in countries where progress is slow or inexistent.


Amino acid sequence of ferredoxin from Physalis alkekengi var. francheti.
The complete amino acid sequence of [2Fe-2S] ferredoxin from Physalis alkekengi var. francheti has been determined by automated Edman degradation of the entire Cm-protein and of the peptides obtained by trypsin and endoproteinase Asp-N digestions. This ferredoxin exhibited ten, ten, and nine differences respectively in the amino acid sequence, when compared with the ferredoxins of Datura stramonium, D. metel, and D. arborea, but 21-28 differences for other angiosperms, and 34-37 differences for fern and horsetails. These results are in harmony with the taxonomic position for these plants.


Issues of instrument translation in research on Asian immigrant populations.
Health disparity research often includes non-English-speaking populations, and instrument translation is a major methodological issue with which researchers must contend. Yet most existing nursing research do not adequately describe translation method processes used. This article describes the procedures used to translate the Caregiver Reaction Assessment instrument into Ilocano for use in a study with elderly Filipinos caring for their grandchildren and the Parenting Practice Interview into Korean for use in a study of parenting practices among Korean immigrant parents. An explanation of Brislin's method for instrument translation is first provided, followed by a detailed description of how this method was applied in the two studies and the challenges encountered in assessing translation accuracy. Achieving semantic and content equivalence posed a major challenge in both studies. Recommendations for cross-cultural nursing research are provided; the experiences described in this article illuminate translation issues to be considered by nurse researchers.


Microbiology of early CF lung disease.
Recent bronchoscopy studies using assays to measure inflammation and molecular typing techniques have facilitated an increased understanding of the early events that occur within the lungs of young children with cystic fibrosis and provided additional insights into the natural history of lung disease in children. In 2000, the US CF National Patient Registry data showed that among 1000 infants <2 years of age, the first bacterial pathogens detected are Haemophilus influenzae, Staphylococcus aureus, and Pseudomonas aeruginosa and the prevalence of these pathogens in these young infants are 19%, 42%, and 29%, respectively. In addition, 7% harbour Stenotrophomonas maltophilia and <1% harbour Burkholderia cepacia complex. Several investigators have performed bronchoscopy studies on young infants to further examine the natural history of lung disease. In one such study of 40 CF infants, 65%, 63% and 70% of children at 1, 2, and 3 years of age harboured at least one CF pathogen. H. influenzae was most common (38%) in infants at 1 year of age, and S. aureus was most common in 2 (37%) and 3 (36%) year olds. P. aeruginosa increased from 18% at 1 year of age to 33% at 3 years of age and was usually present in high numbers, i.e., > or =10(5) CFU/ml of BAL fluid. Investigators have studied the microbiology of young CF infants using specimens derived from the upper airway (deep throat) compared with the lower airway (broncheoalveolar lavage specimens) to determine if the upper airway is predictive of pathogens in the lower airway. In general, these studies have shown that a negative oropharyngeal culture indicated that isolation of P. aeruginosa from the lower airway was unlikely, but a positive culture did not predict lower airway infection. Similar findings were noted for H. influenzae and S. aureus.


Fluralaner (Bravecto®) treatment kills Aedes aegypti after feeding on Dirofilaria immitis-infected dogs.
Transmission of canine heartworm (Dirofilaria immitis) from infected to naïve dogs is dependent on successful mosquito feeding and survival. To determine whether treating heartworm-infected dogs with fluralaner (Bravecto®) limits the survival of infected mosquitoes, and potentially the transmission of D. immitis, we allowed female mosquitoes to feed on microfilaremic dogs and evaluated mosquito survival and infection with D. immitis. Eight dogs were experimentally infected with D. immitis. On day 0 (~ 11 months post-infection), four microfilaremic dogs were treated with fluralaner according to label directions while the other four were non-treated controls. Mosquitoes (Aedes aegypti Liverpool) were allowed to feed on each dog on days -7, 2, 30, 56, and 84. Fed mosquitoes were collected, and the number of live mosquitoes determined at 6 h, 24 h, 48 h, and 72 h post-feeding. Surviving mosquitoes held for 2 weeks were dissected to confirm third-stage D. immitis larvae; PCR (12S rRNA gene) was performed post-dissection to identify D. immitis in mosquitoes. Prior to treatment, 98.4%, 85.1%, 60.7%, and 40.3% of mosquitoes fed on microfilaremic dogs were alive at 6 h, 24 h, 48 h, and 72 h post-feeding, respectively. Similarly, mosquitoes fed on microfilaremic, non-treated dogs were alive 6 h post-feeding (98.5-100%) throughout the study. In contrast, mosquitoes fed on fluralaner-treated dogs 2 days after treatment were dead or severely moribund by 6 h post-feeding. At 30 and 56 days post-treatment, > 99% of mosquitoes fed on treated dogs were dead by 24 h. At 84 days post-treatment, 98.4% of mosquitoes fed on treated dogs were dead by 24 h. Before treatment, third-stage larvae of D. immitis were recovered from 15.5% of Ae. aegypti 2 weeks after feeding, and 72.4% were positive for D. immitis by PCR. Similarly, 17.7% of mosquitoes fed on non-treated dogs had D. immitis third-stage larvae 2 weeks after feeding, and 88.2% were positive by PCR. Five mosquitoes fed on fluralaner-treated dogs survived 2 weeks post-feeding, and 4/5 were from day 84. None had third-stage larvae at dissection, and all were PCR-negative. The data indicate that fluralaner treatment of dogs kills mosquitoes and thus would be expected to reduce transmission of heartworm in the surrounding community.


[Premorbid adjustment and quality of life in schizophrenia].
The Premorbid Adjustment Scale by Cannon-Spoor (PAS) is a rating scale which was designed to evaluate the degree of achievement of developmental goals at each of several periods of a subject's life before the onset of schizophrenia. The evaluation of PAS in schizophrenic patients. In this study premorbid adjustment level was correlated with QOL (Quality of Life Scale (QLS) by Henrichs) in a group of 120 subjects that fulfilled ICD-10 criteria for schizophrenia. This study supported that poor premorbid adjustment can be manifested by poorer QOL among schizphrenics, especially, the lower adjustment in adolecscence, the poorer QOL.


Signal enhancement through heteronuclear polarisation transfer in in-vivo 31P MR spectroscopy of the human brain.
Significant (31)P NMR signal enhancement through heteronuclear polarisation transfer was obtained in model solutions and in vivo on a 1.5-T whole-body MR scanner equipped with two RF channels. The much higher population differences involved in proton Zeeman energy levels can be transferred to the (31)P levels with the refocused INEPT (insensitive nucleus enhancement by polarisation transfer) double-resonance experiment by means of a series of simultaneously applied broadband RF pulses. INEPT achieves a polarisation transfer from (1)H to (31)P spin states by directly reordering the populations in spin systems with heteronuclear scalar coupling. Thus, only the (31)P NMR signal of metabolites with scalar (1)H-(31)P coupling is amplified, while the other metabolite signals in the spectra are suppressed. Compared to Ernst-angle excitation, a repetition-time-dependent signal enhancement of eta=(29+/-3)% for methylene diphosphonic acid (MDPA) and eta=(56+/-1)% for phosphorylethanolamine (PE) was obtained on model solutions through optimisation of the temporal parameters of the pulse experiment. The results are in good agreement with numerical calculations of the theoretical model for the studied spin systems. With optimised echo times, in-vivo (31)P signal enhancement of the same order was obtained in studies of the human brain.


Characterizing household emergency preparedness levels for natural disasters during the COVID-19 pandemic: United States, 2020-2021.
It is vital that households are prepared for a natural disaster to help mitigate potential negative impacts. Our goal was to characterize United States household preparedness on a national level to guide next steps to better prepare for and respond to disasters during the COVID-19 pandemic. We added 10 questions to the existing Porter Novelli's ConsumerStyles surveys in fall 2020 (N = 4,548) and spring 2021 (N = 6,455) to examine factors that contribute to overall household preparedness levels. Being married (odds ratio (OR), 1.2), having children in the home (OR, 1.5), and having a household income of $150,000 or more (OR, 1.2) are all associated with increased preparedness levels. Those in the Northeast are least likely to be prepared (OR, 0.8). Persons living in mobile homes, Recreational Vehicles, boats, or vans are half as likely to have preparedness plans compared to those living in single family homes (OR, 0.6). As a nation, there is much work to be done in terms of preparedness to reach performance measure targets of 80 percent. These data can help inform response planning and the updating of communication resources such as websites, fact sheets, and other materials to reach a wide audience of disaster epidemiologists, emergency managers, and the public.


The effect of poverty on the relationship between household education levels and obesity in U.S. children and adolescents: an observational study.
Although ample evidence has shown the link between childhood obesity and socioeconomic status including family income and household education levels, the mediating role of poverty in the association between household education levels and childhood obesity is unclear. This study aimed to quantify the extent to which family poverty levels contribute to the association between household education levels and obesity among US children and adolescents. This cohort study used the nationally representative data of 21,754 US children and adolescents aged 6-17 years (National Health and Nutrition Examination Survey 1999-2018). We applied mediation analysis of the association between household education levels (less than high school, high school, and college or above) and obesity mediated through poverty (≤138% vs. >138% federal poverty level), adjusting for demographic characteristics of household head and their offspring. Obesity was defined as age- and sex-specific body mass index in the 95th percentile or greater using the 2000 Centers for Disease Control and Prevention growth charts. Among 21,754 children and adolescents (weighted N = 43,544,684; mean age, 11.6 years; female, 49%), 9720 (weighted percentage, 33.0%) were classified as living in poverty and 4671 (weighted percentage, 19.1%) met the criteria for obesity. Low household education level (less than high school) showed increased risks of poverty (adjusted relative risk [95% CI], 5.82 [4.90-6.91]) and obesity (adjusted relative risk [95% CI], 1.94 [1.68-2.25]) compared to high household education level (college or above). We also quantified that poverty mediated 18.9% of the association between household education levels and obesity among children and adolescents. The mediation effect was consistently observed across age, gender, and race/ethnicity. Poverty mediated the association between the low educational status of household heads and their offspring's obesity. Our findings highlight the importance of reducing obesity risk among the low-income population to minimize the burden of intergenerational health disparities due to socioeconomic status. Japan Society for the Promotion of Sciences (22K17392).


Influence of hyperbaric oxygenation on bilirubin and ditaurobilirubin auto-oxidation and porphyrin-sensitized photo-oxidation.
Oxygen concentration controls the reaction rate of porphyrin-sensitized photo-oxidation under constant experimental conditions. The rate of bilirubin and ditaurobilirubin auto-oxidation and meso-tetra-(4-sulphonatophenyl) porphine-sensitized photo-oxidation in aqueous solution increases by about 3.5 times in 0.5 MPa of oxygen. Use of hyperbaric oxygenation in the photodynamic therapy of tumours and in the phototherapy of jaundice is proposed.


Enhanced RNA and protein synthesis in vitro in astrocytes derived from rats in the early stage of experimental hepatogenic encephalopathy.
Astroglia-enriched cell fractions derived from rats with the early symptoms of hepatogenic encephalopathy (HE) following treatment with thioacetamide, showed an increase above control ability to incorporate radioactive precursors into RNA and proteins. These results lend support to the idea that overall stimulation of macromolecular syntheses is an important aspect of astroglial reaction preceding the appearance in astrocytes of progressive morphological changes characterizing more advanced stages of HE.


Cholesterol depletion inhibits the degradation of amyloid beta-peptide in rat pheochromocytoma (PC12) cells.
Amyloid beta-peptide (Abeta) is a very important pathogenic factor for Alzheimer's disease (AD). It is a constitutive product of cellular metabolism and occurs in normal biological fluids, such as CSF and plasma. As the steady state levels of all peptides in vivo are a direct consequence of the balance between their anabolism and catabolism, peptide accumulation can arise not only from increased production but also from decreased breakdown. Although increasing evidence indicates that cholesterol is a risk factor for AD development, the exact mechanisms of cholesterol on Abeta metabolism or deposition have remained unclear. Here, we focus our attention on the effect of cholesterol depletion on the degradation of Abeta1-40. Cholesterol depletion of cultured rat pheochromocytoma (PC12) cells was achieved by methyl-beta-cyclodextrin (MbetaCD) extraction. It was found that cholesterol depletion by MbetaCD extraction can suppress Abeta degradation in PC12 cells.


A mutation that converts serine340 of the HsdSK polypeptide to phenylalanine and its effects on restriction and modification in Escherichia coli K-12.
A hybrid hsdS gene, encoding the HsdSts + d polypeptide, was constructed by joining the proximal region of the wild-type (wt) hsdS sequence with the distal region of the hsdSts + d sequence, at the hsdS BglII site. The hybrid hsdS-Sts + d gene exerts a trans-dominant effect on restriction and modification, which points to the location of the temperature-sensitive (ts) trans-dominant (+ d) mutation in the gene hsdSts + d distal region. Sequencing of the region downstream from the HindIII target in the Escherichia coli K-12 hsdSts + d mutant was carried out. It is identical to the wt hsdS sequence (GenBank/EMBL accession number ECHSDK LV00288), except for a single base-pair transition C1245----T. The results obtained support the idea that the trans-dominant effect of the ts mutation described earlier is related to the single base-pair transition in the nonhomologous region of the hsdSts + d sequence.


Monitoring uterine contractions during labor: current challenges and future directions.
Organ-level models are used to describe how cellular and tissue-level contractions coalesce into clinically observable uterine contractions. More importantly, these models provide a framework for evaluating the many different contraction patterns observed in laboring patients, ideally offering insight into the pitfalls of currently available recording modalities and suggesting new directions for improving recording and interpretation of uterine contractions. Early models proposed wave-like propagation of bioelectrical activity as the sole mechanism for recruiting the myometrium to participate in the contraction and increase contraction strength. However, as these models were tested, the results consistently revealed that sequentially propagating waves do not travel long distances and do not encompass the gravid uterus. To resolve this discrepancy, a model using 2 mechanisms, or a "dual model," for organ-level signaling has been proposed. In the dual model, the myometrium is recruited by action potentials that propagate wave-like as far as 10 cm. At longer distances, the myometrium is recruited by a mechanotransduction mechanism that is triggered by rising intrauterine pressure. In this review, we present the influential models of uterine function, highlighting their main features and inconsistencies, and detail the role of intrauterine pressure in signaling and cervical dilation. Clinical correlations demonstrate the application of organ-level models. The potential to improve the recording and clinical interpretation of uterine contractions when evaluating labor is discussed, with emphasis on uterine electromyography. Finally, 7 questions are posed to help guide future investigations on organ-level signaling mechanisms.


Crystal structure of the post-fusion core of the Human coronavirus 229E spike protein at 1.86 Å resolution.
Human coronavirus 229E (HCoV-229E) usually causes mild upper respiratory infections in heathy adults, but may lead to severe complications or mortality in individuals with weakened immune systems. Virus entry of HCoV-229E is mediated by its spike (S) protein, where the S1 domain facilitates attachment to host cells and the S2 domain is involved in subsequent fusion of the virus and host membranes. During the fusion process, two heptad repeats, HR1 and HR2, in the S2 domain assemble into a six-helix membrane-fusion structure termed the fusion core. Here, the complete fusion-core structure of HCoV-229E has been determined at 1.86 Å resolution, representing the most complete post-fusion conformation thus far among published human alphacoronavirus (α-HCoV) fusion-core structures. The overall structure of the HCoV-229E fusion core is similar to those of SARS, MERS and HCoV-NL63, but the packing of its 3HR1 core differs from those of SARS and MERS in that it contains more noncanonical `x' and `da' layers. Side-by-side electrostatic surface comparisons reveal that the electrostatic surface potentials are opposite in α-HCoVs and β-HCoVs at certain positions and that the HCoV-229E surface also appears to be the most hydrophobic among the various HCoVs. In addition to the highly conserved hydrophobic interactions between HR1 and HR2, some polar and electrostatic interactions are also well preserved across different HCoVs. This study adds to the structural profiling of HCoVs to aid in the structure-based design of pan-coronavirus small molecules or peptides to inhibit viral fusion.


Laser-triggered combination therapy by iron sulfide-doxorubicin@functionalized nanozymes for breast cancer therapy.
The use of magnetic nanozymes (NZs) with the ability to synchronize gas therapy through photodynamic and chemotherapy in the treatment of breast cancer has received much attention. Hence, in this study, we designed a bovine lactoferrin-coated iron sulfide NZs containing doxorubicin (abbreviated as: FeS-Dox@bLf NZs) by wet-chemical synthesis method. Then, the physicochemical characteristics of synthesized NZs were explored by several methods. Also, the level of Fe2+, H2S and Dox releases from FeS-Dox@Lf NZs. Also, the cytotoxic effects of FeS-Dox@Lf NZs were investigated by cellular assays. After intravenous injections of NZs and laser irradiation, significant effects of FeS-Dox@Lf NZs on mice weight and tumor status were observed. Afterwards, not only the distribution of Dox in the body was examined by fluorescent, but also the time of Fe clearance and the amount of Dox and Fe retention in vital tissues were determined. The findings confirm that FeS-Dox@Lf NZs, in addition to targeted drug distribution in tumor tissue, resulted in superior therapeutic performance compared to free Dox due to reduced Dox side effects in vital tissues, and increased level of free radicals in 4T1 cells. Overall, FeS-Dox@Lf NZs with the ability to synchronize chemotherapy and gas therapy raised hopes for more effective treatment of breast cancer.


Portraying disease: Sorolla's Sad Legacy.
In 1899, the Spanish painter Joaquín Sorolla represented, in a large canvas, a group of children probably with sequels of poliomyelitis bathing at Valencia's beach. The title of this painting was Sad Legacy. This work contributed to the international diffusion of Sorolla's artistic creation. We briefly report some facts regarding the painter and his work referring to those portraits of children and especially of sick children.


Feasibility of MR imaging in evaluating breast cancer lymphangiogenesis using Polyethylene glycol-GoldMag nanoparticles.
To investigate the feasibility of evaluating tumour lymphangiogenesis using magnetic resonance imaging (MRI) in vivo. Water-soluble polyethylene glycol (PEG)-GoldMag nanoparticles were obtained by combining GoldMag with PEG. The PEG-GoldMag nanoparticles were bound to anti-podoplanin antibody (PodAb) to construct PEG-GoldMag-pod molecular probes targeting lymphatic endothelial cells (LECs). The characteristics of the PEG-GoldMag-pod nanoparticles were tested. Using these nanoparticles, tumour lymphangiogenesis was evaluated using MRI in vitro and in vivo. The average size of PEG-GoldMag nanoparticles was about 66.8 nm, and the nanoparticles were stably dispersed in the liquid phase for at least 15 days. After incubation for 24 h at different iron concentrations ranging from 5-45 μg/ml, the LECs were labelled with PEG-GoldMag-pod nanoparticles, in particular the breast cancer LECs. Dose-dependence was observed in the labelling efficiencies and MRI images of the labelled cells. In vitro, the labelling efficiencies and MRI images showed that the nanoparticles could detect podoplanin expression in LECs. In induced rat models of breast cancer, PEG-GoldMag-pod nanoparticles combined with lymphatic vessels were significantly detectable at MRI 60 min after nanoparticle administration, the signal intensity was negatively correlated with the lymphatic vessel density of breast cancer (r = -0.864, P = 0.000). The present study proves the feasibility of evaluating tumour lymphangiogenesis with MRI in vivo.


Fine-needle aspiration of neural lesions.
The cytomorphologic features of 13 neural lesions sampled by fine-needle aspiration (FNA) are reviewed. The frequencies at which various architectural features including Verocay bodies, filamentous background, and vascular arcades were present was recorded, along with the frequencies of cytologic findings including the presence of spindle cells, wavy nuclei, intranuclear inclusions, fishhook nuclei, nuclear pleomorphism, filamentous cytoplasm, and mitotic figures. Verocay bodies were a rare finding, present in only 1 of 11 cases. Vascular arcades were similarly infrequent (1/11 cases). Spindle-shaped cells along with wavy nuclei were the most frequent findings, with fishhook-shaped nuclei and a filamentous background of high frequency (9/11 cases). Our study indicates that some of the characteristic features recorded in the literature are rarely seen in needle aspiration smears, but features such as spindle-shaped cells, wavy and fishhook-shaped nuclei, and a filamentous background are relatively frequent findings.


Experimental double infection of Biomphalaria glabrata snails with Angiostrongylus cantonensis and Schistosoma mansoni.
Two groups of Biomphalaria glabrata snails primarily infected with Angiostrongylus contonensis were secondarily exposed to infection with Schistosoma mansoni. To investigate any anatagonistic effect of the first infection on a superimposed one and to compare to singly and non-infected snails, a series of experiments was undertaken in which snails were individually exposed, variously, to 1,000 and 2,000 first-stage larvae of A. cantonensis and then to 5 and 10 miracidia of S. mansoni 1 day and 3 weeks later. Snails became infected with S. mansoni in both groups of snails with double infections and shed cercariae after the same incubation period as in the singly infected groups. The number of snails shedding cercariae simultaneously was similar in single and double infection groups during the first two weeks of shedding, after which this number decreased somewhat in doubly infected groups. Snails with double infection showed higher cumulative mortality rates than in snail groups with single infection with either A. cantonensis or S. mansoni. Therefore, initial infection of B. glabrata with A. cantonensis produced no inhibitory or retarding effect on subsequent infection of snails with S. mansoni.


Designed Ankyrin Repeat Protein (DARPin) to target chimeric antigen receptor (CAR)-redirected T cells towards CD4+ T cells to reduce the latent HIV+ cell reservoir.
Chimeric Antigen Receptor (CAR)-redirected T cells show great efficacy in the patient-specific therapy of hematologic malignancies. Here, we demonstrate that a DARPin with specificity for CD4 specifically redirects and triggers the activation of CAR engineered T cells resulting in the depletion of CD4+ target cells aiming for elimination of the human immunodeficiency virus (HIV) reservoir.


Aluminium leaching from red mud by filamentous fungi.
This contribution investigates the efficient and environmentally friendly aluminium leaching from red mud (bauxite residue) by 17 species of filamentous fungi. Bioleaching experiments were examined in batch cultures with the red mud in static, 7-day cultivation. The most efficient fungal strains in aluminium bioleaching were Penicillium crustosum G-140 and Aspergillus niger G-10. The A. niger G-10 strain was capable to extract up to approximately 141 mg·L(-1) of aluminium from 0.2 g dry weight red mud. Chemical leaching with organic acids mixture, prepared according to A. niger G-10 strain's respective fungal excretion during cultivation, proved that organic acids significantly contribute to aluminium solubilization from red mud.


Health aspects of the Tsunami disaster in Asia.
This is a summary of the proceedings of the Conference on the Health Aspects of the Tsunami Disaster in Asia that was convened by the World Health Organization in Phuket, Thailand from 04-06 May 2005. It contains reviews of the experiences of the health sector and early recovery following the Earthquake and Tsunami with emphasis on what was done well and what could have been done better and the lessons learned that can be incorporated into actions that will mitigate the damage created by future events. It outlines the national and international responses and recovery and the actions taken and not taken by the international community in support of the countries affected. Specific issues addressed include: (1) needs assessments; (2) coordination; (3) filling gaps in essential services, and (4) capacity building at the country level. Each of these aspects is analyzed as to its: (1) appropriateness; (2) adequacy; (3) effectiveness; (4) efficiency; and (5) connectedness. Much of what occurred provided benefits to the stricken population, but there is substantial room for improvement through implementation of the lessons learned. These lessons must be converted into actions in order to mitigate the damage sustained and to enhance our responses to the damage from future events.


Double-stranded RNA-mediated interference of dumpy genes in Bursaphelenchus xylophilus by feeding on filamentous fungal transformants.
RNA interference (RNAi) is a valuable tool for studying gene function in vivo and provides a functional genomics platform in a wide variety of organisms. The pinewood nematode, Bursaphelenchus xylophilus, is a prominent invasive plant-parasitic nematode and has become a serious worldwide threat to forest ecosystems. Presently, the complete genome sequence of B. xylophilus has been published, and research involving genome-wide functional analyses is likely to increase. In this study, we describe the construction of an effective silencing vector, pDH-RH, which contains a transcriptional unit for a hairpin loop structure. Utilising this vector, double-stranded (ds)RNAs with sequences homologous to the target genes can be expressed in a transformed filamentous fungus via Agrobacterium tumefaciens-mediated transformation technology, and can subsequently induce the knockdown of target gene mRNA expression in B. xylophilus by allowing the nematode to feed on the fungal transformants. Four dumpy genes (Bx-dpy-2, 4, 10 and 11) were used as targets to detect RNAi efficiency. By allowing the nematode to feed on target gene-transformed Fusarium oxysporum strains, target transcripts were knocked down 34-87% compared with those feeding on the wild-type strain as determined by real-time quantitative PCR (RT-qPCR). Morphological RNAi phenotypes were observed, displaying obviously reduced body length; weak dumpy or small (short and thin) body size; or general abnormalities. Moreover, compensatory regulation and non-specific silencing of dpy genes were found in B. xylophilus. Our results indicate that RNAi delivery by feeding in B. xylophilus is a successful technique. This platform may provide a new opportunity for undertaking RNAi-based, genome-wide gene functional studies in vitro in B. xylophilus. Moreover, as B. xylophilus feeds on endophytic fungi when a host has died, RNAi feeding technology will offer the prospect for developing a novel control strategy for the nematode. Furthermore, this platform may also be applicable to other parasitic nematodes that have a facultative, fungivorous habit.


Expression of the proto-oncogenes c-met and c-kit and their ligands, hepatocyte growth factor/scatter factor and stem cell factor, in SCLC cell lines and xenografts.
We examined a panel of 25 small cell lung cancer (SCLC) cell lines and nude mouse xenografts for expression of the proto-oncogenes c-met and c-kit, and for expression of the corresponding ligands, hepatocyte growth factor (HGF) (also known as scatter factor (SF)), and stem cell factor (SCF), respectively. Expression of mRNA was detected by Northern blotting, and c-met and c-kit protein expression was detected by Western blotting and immunocytochemistry. c-met and c-kit mRNA was expressed in 22 of the examined cell lines or xenografts, and coexpression of the two proto-oncogenes was observed in 20 tumours. Expression of c-met and c-kit protein paralleled in the mRNA expression. HGF/SF mRNA was expressed in two of the examined tumours, and only one of these also expressed the c-met proto-oncogene. SCF mRNA was expressed in 19 of the examined tumours, and in 18 of these coexpression of c-kit and SCF was present. The high percentage of SCLC tumours expressing c-met and c-kit indicates that these proto-oncogenes may have an important function in this disease. The rare coexpression of c-met and HGF/SF is evidence that an autocrine regulatory pathway is not present for this receptor/ligand system in SCLC, while the frequent coexpression of c-kit and SCF indicates that this receptor/ligand system may have an autocrine function in SCLC.


The role of noninvasive scoring systems for predicting cardiovascular disease risk in patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis.
Cardiovascular disease (CVD) is suggested as a leading cause of death among patients with nonalcoholic fatty liver disease (NAFLD). The aim of this work was to clarify the role of noninvasive scoring systems (NSSs) in predicting CVD risk among this population. The PubMed, Web of Science, and Cochrane databases were searched until 23 March 2022. Meta-analysis was performed for three most commonly used NSS separately, that is, fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and AST/platelet ratio index (APRI). Totally, nine studies including 155 382 patients with NAFLD were enrolled. Patients with NAFLD had a higher risk of CVD with increasing FIB-4 score (1.94, 1.52-2.46), the association remained significant after adjustment for age, sex, body mass index, hypertension, and diabetes (2.44, 1.85-3.22). Similarly, a higher risk of CVD was also observed in patients with increasing NFS (2.17, 1.58-2.98) and APRI scores (1.36, 1.04-1.79) in the unadjusted model. However, in the adjusted model, the association was significant only for NFS (3.83, 1.40-10.43), but not for APRI (1.41, 0.79-2.51). Additionally, the increment in CVD risk was most noticeable in subgroup of FIB > 2.67 vs. FIB ≤ 1.3 (6.52, 3.07-13.86) and subgroup of NFS > 0.676 vs. NFS ≤ -1.455 (16.88, 5.68-50.23). All subgroup analyses showed significant associations between FIB-4, NFS, and risk of CVD. Sensitivity analyses did not modify these results. FIB-4 and NFS might be useful in identifying those who are at higher risk of CVD among patients with NAFLD. However, APRI was not recommended for this use.


Pattern visual evoked potential and foveal sensitivity in amblyopia.
Amblyopic eyes show impaired visual functions such as poor visual acuity and reduced foveal sensitivity. The purpose of this study was to determine the association between foveal threshold and visual evoked potentials (VEP) in strabismic and anisometropic amblyopia. Forty-five subjects (age range: 7-28 years, 43.3% female) including 15 strabismic and 15 anisometropic amblyopes, and 15 age-similar control subjects participated in this study. Each subject had pattern visual evoked potentials and foveal threshold recorded in each eye using RetiScan (Roland Consult, Germany) and Humphrey Visual Field Analyzer II (HFA II; Carl Zeiss Meditec Inc., Dublin, CA), respectively. These outcomes were compared among the amblyopic eyes, their fellow eyes, and the control eyes. Compared to the amblyopic eyes (Mean ± SD: 33.4 ± 3.48 dB), the foveal threshold was higher in fellow eyes (37.0 ± 2.04 dB, p = 0.0002) and in control eyes (38.7 ± 0.96 dB, p < 0.0001). Strabismic amblyopes had a lower foveal threshold than anisometropic amblyopes (31.8 ± 3.86 vs. 35.0 ± 2.17 dB, p = 0.005). Relative to the P100 peak time in fellow eyes (1° checks:116.1 ± 9.00 ms; 0.25° checks:118.8 ± 5.67 ms), amblyopic eyes had delayed P100 peak times for both 1° (122.7 ± 11.4 ms, p < 0.0001) and 0.25° (130.4 ± 11.2 ms, p < 0.0001) check sizes. There were also significant differences in P100 peak time between amblyopic and control eyes (1°:122.7 ± 11.4 vs.112.4 ± 5.01 ms, p = 0.15; 0.25°:130.4 ± 11.2 vs.113.9 ± 5.71 ms, p < 0.0001) and between fellow and control eyes (0.25°:118.8 ± 5.67 vs.113.9 ± 5.71 ms, p = 0.009). Amblyopic eyes exhibited lower N75-P100 amplitudes than fellow eyes (1°:12.6 ± 7.96 vs.15.9 ± 8.82 µV, p = 0.01; 0.25°:10.6 ± 6.11 vs. 15.8 ± 10.6 µV, p = 0.001) and control eyes (0.25°: p = 0.0008). Foveal threshold correlated negatively with P100 peak time (1°: r = -0.45, p = 0.002 and 0.25°: r = -0.58, p < 0.0001) and positively with N75-P100 amplitude responses (1°: r = 0.42, p = 0.004 and 0.25°: r = 0.52, p = 0.002). Amblyopic eyes showed reduced pattern VEP amplitudes and delayed peak times with significant associations with the foveal sensitivity. However, the VEP measures overlapped extensively between amblyopic and control eyes with no apparent criterion value for optimal discrimination, suggesting that foveal sensitivity might be a better discriminator of amblyopia than pattern VEP.


Cardiovascular fitness, insulin resistance and metabolic syndrome in severely obese prepubertal Italian children.
To evaluate if insulin resistance (IR) and metabolic syndrome (MS) were associated with poor cardiovascular fitness in very obese prepubertal Italian subjects. Children referred to the Endocrinology and Diabetes Unit of Bambino Gesù Children's Hospital underwent an OGTT with glucose and insulin assays. QUICKI, ISI and HOMA-IR were calculated. Total and HDL cholesterol, triglycerides and percentage of body fat (DEXA) were determined. Cardiovascular fitness (maximal treadmill time) was evaluated using a treadmill protocol. The MS was defined as having 3 or more of following risk factors: obesity, impaired glucose tolerance, high blood pressure, low HDL-cholesterol, high triglycerides. Fifty-five very obese prepubertal Italian children were enrolled in the study. Unadjusted correlation revealed maximal treadmill time negatively related to fasting insulin (r = -0.53, p < 0.0001) and HOMA-IR (r = -0.57, p < 0.0001) and positively to QUICKI (r = 0.51, p < 0.0001) and ISI (r = 0.46, p = 0.0035). These relationships remained significant when in multivariate analysis age, gender, BMI SD and body composition were accounted for (all p < 0.01). The presence of the MS was independently associated with maximal treadmill time. Poorcardiovascular fitness, IR and MS were independently related, suggesting that the relationship between fitness and insulin action develops early in life.


Liposomal formulations of inflammatory bowel disease drugs: local versus systemic drug delivery in a rat model.
Based on adherence to intestinal mucosa, intralumenally administered liposomal formulations of 5-aminosalicylate (5-ASA) and 6-mercaptopurine (6-MP) were studied for their potential to enhance local drug delivery to intestinal tissue for the treatment of inflammatory bowel disease. 5-ASA was encapsulated in standard phospholipid liposomes while 6-MP required encapsulation in nonphospholipid liposomes to obtain equivalent drug loading. Encapsulation efficiency was measured by size-exclusion chromatography/high-performance liquid chromatogtaphy (HPLC). Liposomal formulations or solution of the drugs were injected into unligated jejunum to compare pharmacokinetics and into ligated loops of rat ileum and colon to evaluate local delivery. Dextran sulfate and acetic acid induced colitis were used as models of lower intestinal inflammation. Plasma, tissue and luminal drug and metabolite levels were measured by liquid scintillation counting or HPLC. Encapsulation efficiency of 6-MP was dependent on lipid content and composition. While liposomal encapsulation significantly reduced systemic absorption of 5-ASA this was not the case for 6-MP. Liposomal adherence to intestinal tissue resulted in increased tissue levels for 5-ASA; however, 6-MP local tissue levels were not improved compared to solution drug. Nonphospholipid liposomes optimize encapsulation of 6-MP. While liposomal formulations show potential for local drug delivery to diseased bowel, drug physicochemical properties, absorption, and metabolic profiles dictate tissue-targeting potential. Liposomes reduce systemic availability from paracellular absorption of hydrophilic 5-ASA, but fail to improve local tissue delivery of 6-MP, a molecule absorbed by passive membrane permeation that undergoes extensive first- pass metabolism.


Comparison of the maximum coagulation depth in human skin for different types of medical lasers.
The values for the maximum coagulation depth (MCD) of various types of lasers which are specified in the literature are not comparable, because often different irradiation times were used. MCD depends not only on the wavelength of laser light, but also on the time of action of the laser beam, because of heat transfer. In excised human skin MCD was determined histologically for irradiation with the argon laser, Nd:YAG laser, and CO2 laser. Extending the irradiation time from 0.2 s to 10 s results in a 4-6-fold increase in MCD. Coagulation experiments performed with a soldering iron have shown results similar to those obtained with the CO2 laser. Enlargement of the laser-beam diameter from 1 to 2 mm leads to a 50% increase in MCD. Additional chilling of the skin with water during laser irradiation protects the skin from evaporation, and the values for MCD increase to 3.5 mm for the argon laser and 5.5 mm for Nd:YAG laser. Detailed knowledge of the MCD is necessary to obtain the desired therapeutic effect, and also to avoid unwanted effects.


A digestive prolyl carboxypeptidase in Tenebrio molitor larvae.
Prolyl carboxypeptidase (PRCP) is a lysosomal proline specific serine peptidase that also plays a vital role in the regulation of physiological processes in mammals. In this report, we isolate and characterize the first PRCP in an insect. PRCP was purified from the anterior midgut of larvae of a stored product pest, Tenebrio molitor, using a three-step chromatography strategy, and it was determined that the purified enzyme was a dimer. The cDNA of PRCP was cloned and sequenced, and the predicted protein was identical to the proteomic sequences of the purified enzyme. The substrate specificity and kinetic parameters of the enzyme were determined. The T. molitor PRCP participates in the hydrolysis of the insect's major dietary proteins, gliadins, and is the first PRCP to be ascribed a digestive function. Our collective data suggest that the evolutionary enrichment of the digestive peptidase complex in insects with an area of acidic to neutral pH in the midgut is a result of the incorporation of lysosomal peptidases, including PRCP.


Anaphylaxis due to ruptured pulmonary hydatid cyst in a 13-year-old boy.
Hydatid cyst, a common disease in the world, is usually transmitted to humans through dog feces. Hydatid cyst is caused by Echinococcus granulosus. Diagnostic interventions for hydatid cyst include physical examination and chest x-ray tomography. Although the treatment options of hydatid cyst vary according to the clinical findings of the patients, the primary treatment may be considered as surgery. We herein reported the case of a child hospitalized due to pneumonia who developed anaphylaxis as a result of the rupture of a pulmonary hydatid cyst.


Linguistic distancing predicts response to a digital single-session intervention for adolescent depression.
Examining the linguistic characteristics of youths' writing may be a promising method for detecting youth who are struggling. In this study, we examined linguistic patterns of adolescent responses to writing prompts in a large, well-powered trial of an evidence-based, digital single-session intervention teaching malleability beliefs about personal traits and symptoms ("growth mindset"). Participants who completed the intervention as part of a larger randomized control trial were included in this preregistered study (n = 638, https://osf.io/zqmxt). Participants' responses were processed using Linguistic Inquiry and Word Count. We tested correlations between linguistic variables (i.e., linguistic distancing, positive affect, negative affect, insight, certainty), baseline outcome variables, post-intervention outcome variables, and 3-month post-intervention outcome variables. We also used Least Absolute Shrinkage and Selection Operator (LASSO) regression models to identify key predictors of treatment outcomes. As hypothesized, greater use of linguistic distancing was associated with lower levels of baseline hopelessness and higher levels of perceived agency. Additionally, per LASSO models including all linguistic variables, greater use of linguistic distancing predicted larger reductions in depressive symptoms from baseline to three-month follow-up. Linguistic distancing appeared to account for 27% of the variance in depression trajectories when also accounting for baseline depression. CLINICAL REGISTRATION NO: NCT04634903.


Correction: Lamy et al. Monitoring Solar Radiation UV Exposure in the Comoros. Int. J. Environ. Res. Public Health 2021, 18, 10475.
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RAFT Polymerization of Semifluorinated Monomers Mediated by a NIR Fluorinated Photocatalyst.
Near-infrared (NIR) light plays an increasingly important role in the field of photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization due to its unique properties. Yet, the NIR photocatalyst with good stability for PET-RAFT polymerization remains promising. Here, a strategy of NIR PET-RAFT polymerization of semifluorinated monomers using fluorophenyl bacteriochlorin as a photocatalyst with strong absorption at the NIR light region (710-780 nm) is reported. In which, the F atoms are used to modify reduced tetraphenylporphyrin structure with enhanced photostability of photocatalyst. Under the irradiation of NIR light (λmax = 740 nm), the PET-RAFT polymerization of semifluorinated methylacrylic monomers presents living/control characteristics and temporal modulation. By the PET-RAFT polymerization-induced self-assembly (PISA) strategy, stable fluorine-containing micelles are constructed in various solvents. In addition, the fluorinated hydrophobic surface is fabricated via a surface-initiated PET-RAFT (SI-PET-RAFT) polymerization using silicon wafer bearing RAFT agents with tunable surface hydrophobicity. This strategy not only enlightens the application of further modified compounds based on porphyrin structure in photopolymerization, but also shows promising potential for the construction of well-defined functional fluoropolymers.


Localization of lumbar epaxial motoneurons in the rat.
In the rat, lateral longissimus and the lumbar transverso-spinalis muscles are lumbar trunk muscles, and participate in the lordosis reflex (female sexual posturing). Medial longissimus, the remaining major lumbar epaxial muscle, is a muscle of the proximal tail-tailbase. To allow an analysis of the motor control of lordosis, motoneurons for these muscles must be localized. Horseradish peroxidase (HRP) was injected into lumbar epaxial muscles of female rats. Following injection into medial longissimus, labeled cells were found posterior to the lumbar enlargement, ventrolaterally in the ventral horn. Following injections into lateral longissimus or into lumbar transverso-spinalis muscles, most labeled cells were found on the medial side of the ventral horn, extending through and anterior to the lumbar enlargement. Injections into lumbar transverso-spinalis muscles at more posterior levels led to more posterior locations of labeled cells. The distributions of the labeled cells agree with previous observations on innervation of the muscles. Additionally, the spinal cord was scanned for sites at which microstimulation produced visible twitches of medial longissimus or transverso-spinalis muscles. Locations of low threshold twitch sites were consistent with conclusions based on the HRP findings.


Single-Screw Fixation Compared With Double Screw Fixation for Treatment of Medial Malleolar Fractures: A Prospective Randomized Trial.
To determine whether single or double screw (DS) fixation of medial malleolar fractures results in better long-term health outcomes. Randomized clinical trial; sealed envelope technique. Level 1 Trauma Hospital at University of Calgary, Canada. One hundred forty patients were randomized to receive either 1 or 2 screws to reduce a medial malleolar fracture. Thirteen patients were excluded because of loss to follow-up (n = 127). Surgical fixation of the medial malleolar fracture was performed using 1 or 2 stainless steel screws. Primary outcome was comparison of physical functioning summary score on Short Form 36 questionnaires between patients in the 2 groups. Secondary objectives were to compare the Ankle Hindfoot Scale and operating room time. Clinical and radiographic assessment occurred at the time of injury and 2, 6 weeks, 3, 6, 12, and 24 months postoperatively. Fourteen patients crossed over from the DS group to the single screw (SS) group based on intraoperative decisions by the surgeon (fragment too small for 2 screws), leaving the SS (n = 75) and DS groups (n = 52). There was no difference in the operating room time, SF36, or Ankle Hindfoot Scale at all follow-up time points. SS medial malleolar fixation provides an equally safe and effective method of fracture care as compared to DS fixation. Twenty percent of patients receiving 2 screws can be expected to crossover to receive SS fixation as a safer alternative. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.


Factors affecting recurrence and prognosis after R0 resection for colorectal cancer with peritoneal metastasis.
Peritoneal metastases (PM) are a well-known poor prognostic factor. The aim of this study was to investigate the factors affecting recurrence and prognosis after R0 resection for colorectal cancer with synchronous peritoneal metastases. We conducted a multi-institutional retrospective analysis of 72 patients without distant metastases who underwent R0 surgery between 1991 and 2007 for colorectal cancer with PM localized to the adjacent peritoneum. Clinicopathological variables were analyzed for their significance to recurrence and prognosis. Recurrence was found in 51 patients (70.8%) after R0 surgery. In logistic regression analyses, lymph node metastasis was shown to be an independent factor affecting recurrence. Non-intensive or no postoperative chemotherapy and eight or fewer dissected lymph nodes were identified as independent poor prognostic factors using the Cox proportional hazards model. Among patients who received postoperative chemotherapy, prognosis was significantly better in those who received intensive adjuvant chemotherapy using camptothecin-11 or oxaliplatin after R0 surgery than in those who received non-intensive chemotherapy. Among 47 patients whose recurrence date was known, 33 patients (70.2%) experienced recurrence within 18 months after R0 surgery for peritoneal metastases, and hematogenous recurrence was observed significantly more often than peritoneal recurrence. Harvesting of more than eight lymph nodes and administration of intense adjuvant chemotherapy after R0 surgery are recommended for greater prediction accuracy and improved prognosis. Intensive follow-up should be performed within 18 months after R0 surgery for colorectal cancer with synchronous peritoneal metastases.


Radiographic follow-up of diseased temporomandibular joints.
The objective of this study was to assess the long-term course of radiographically evident degenerative changes of the soft and hard tissues of the temporomandibular joint (TMJ) in patients with TMJ disorders. Twenty-one patients (33 joints) were included in the study. The results of radiographic assessments at the first visit and at least 46 months after the first visit (mean 96.0 months) were compared. All subjects had a good clinical course after a favorable response to treatment. Radiographic assessment showed that there was a statistically significant change in disk morphology during the intervening years, with the disks becoming more deformed (P < .05, McNemar test). On the other hand, there was no significant change in the condylar morphology or size. Most of the acute and destructive radiographically visible degenerative changes were arrested or slowed in the patients whose symptoms and signs were successfully resolved or reduced, while disk deformation significantly progressed.


[Titanium-coated hollow screw and reconstruction plate system for the bridging of jaw defects. II. Possible reconstruction variants with the THRP system].
The advantages and special features of the THRP-system enabled us to develop new operative techniques. The combination of the advantages of external fixation devices and those of the internal osteosynthesis has proved to be decisive in order to obtain good results. The clinical results in 30 patients confirm the recently published findings from animal studies. Histological examination of human specimens comparing 2 types of screws developed by us are discussed.


A new regulatory mechanism controlling carotenogenesis in the fungus Mucor circinelloides as a target to generate β-carotene over-producing strains by genetic engineering.
Carotenoids are natural pigments with antioxidant properties that have important functions in human physiology and must be supplied through the diet. They also have important industrial applications as food colourants, animal feed additives and nutraceuticals. Some of them, such as β-carotene, are produced on an industrial scale with the use of microorganisms, including fungi. The mucoral Blakeslea trispora is used by the industry to produce β-carotene, although optimisation of production by molecular genetic engineering is unfeasible. However, the phylogenetically closely related Mucor circinelloides, which is also able to accumulate β-carotene, possesses a vast collection of genetic tools with which to manipulate its genome. This work combines classical forward and modern reverse genetic techniques to deepen the regulation of carotenoid synthesis and generate candidate strains for biotechnological production of β-carotene. Mutagenesis followed by screening for mutants with altered colour in the dark and/or in light led to the isolation of 26 mutants that, together with eight previously isolated mutants, have been analysed in this work. Although most of the mutants harboured mutations in known structural and regulatory carotenogenic genes, eight of them lacked mutations in those genes. Whole-genome sequencing of six of these strains revealed the presence of many mutations throughout their genomes, which makes identification of the mutation that produced the phenotype difficult. However, deletion of the crgA gene, a well-known repressor of carotenoid biosynthesis in M. circinelloides, in two mutants (MU206 and MU218) with high levels of β-carotene resulted in a further increase in β-carotene content to differing extents with respect to the crgA single-null strain; in particular, one strain derived from MU218 was able to accumulate up to 4 mg/g of β-carotene. The additive effect of crgA deletion and the mutations present in MU218 suggests the existence of a previously unknown regulatory mechanism that represses carotenoid biosynthesis independently and in parallel to crgA. The use of a mucoral model such as M. circinelloides can allow the identification of the regulatory mechanisms that control carotenoid biosynthesis, which can then be manipulated to generate tailored strains of biotechnological interest. Mutants in the repressor crgA and in the newly identified regulatory mechanism generated in this work accumulate high levels of β-carotene and are candidates for further improvements in biotechnological β-carotene production.


Aged hematopoietic stem cells entrap regulatory T cells to create a prosurvival microenvironment.
Although DNA mutation drives stem cell aging, how mutation-accumulated stem cells obtain clonal advantage during aging remains poorly understood. Here, using a mouse model of irradiation-induced premature aging and middle-aged mice, we show that DNA mutation accumulation in hematopoietic stem cells (HSCs) during aging upregulates their surface expression of major histocompatibility complex class II (MHCII). MHCII upregulation increases the chance for recognition by bone marrow (BM)-resident regulatory T cells (Tregs), resulting in their clonal expansion and accumulation in the HSC niche. On the basis of the establishment of connexin 43 (Cx43)-mediated gap junctions, BM Tregs transfer cyclic adenosine monophosphate (cAMP) to aged HSCs to diminish apoptotic priming and promote their survival via activation of protein kinase A (PKA) signaling. Importantly, targeting the HSC-Treg interaction or depleting Tregs effectively prevents the premature/physiological aging of HSCs. These findings show that aged HSCs use an active self-protective mechanism by entrapping local Tregs to construct a prosurvival niche and obtain a clonal advantage.


Keratins in malignant mesotheliomas and pleural adenocarcinomas: comparative immunohistochemical analysis with polyclonal and monoclonal antibodies.
The distribution of intra-cellular keratins was studied in normal pleural mesothelium, malignant mesotheliomas and adenocarcinomas. This study was performed on deparaffinized sections of tissue fixed in Bouin's solution by indirect immunofluorescence with a monoclonal antibody (KL1) and a conventional keratin antiserum (AKS). Discrepancies were detected using one antibody or the other. Cells from normal mesothelium and 18 cases of malignant mesotheliomas (papillary, tubulary, solid epithelial type) were strongly labelled only by KL1. The 2 cases of sarcomatoid type were negative with both antibodies. In contrast 5 metastatic adenocarcinomas and 5 lung adenocarcinomas were weakly positive or negative with both antibodies. These data confirm the presence of cytokeratins in epithelial differentiation process. Although a clear-cut distinction between mesotheliomas and adenocarcinomas was not possible using these keratin antibodies. Our data point out the importance of reactivity pattern of the antibody used in such investigations.


Expression of ABCB1, ABCC1 and 3 and ABCG2 in glioblastoma and their relevance in relation to clinical survival surrogates.
Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumors in adults. Patients invariably relapse during or after first-line therapy and the median overall survival is 14.6 months. Such poor clinical response is partly ascribed to the activity of ATP-binding cassette (ABC) transporters. The activity of these proteins, severely reduces the amount of therapeutics that penetrates the tumor cells. We hypothesized that ABC transporter expression could correlate with survival surrogates. In this study, we assessed the expression of four commonly expressed ABC transporters in GBM samples and investigated if mRNA levels could serve as a prognostic biomarker. Human specimens were analyzed by qPCR to assess ABCB1, ABCC1/3 and ABCG2 expression. Kaplan-Meier and multivariate analyses were then used to evaluate the correlation with overall survival (OS) and progression-free survival (PFS). Our cohort included 22 non-tumoral samples as well as 159 GBM tumor specimens. ABC transporters were significantly more expressed in GBM samples compared to non-tumoral tissue. Moreover ABCC1 and 3 mRNA expression were significantly increased at recurrence. Statistical analyses revealed that increased expression of either ABCC1 or ABCC3 did not confer a poorer prognosis. However, increased ABCC1 mRNA levels did correlate with a significantly shorter PFS. In this manuscript, the analyses we conducted suggest that the expression of the four ABC transporters evaluated would not be suitable prognostic biomarkers. We believe that, when estimating prognosis, the plethora of mechanisms implicated in chemoresistance should be analyzed as a multi-facetted entity rather than isolated units.


Psychometric Evaluation of the Swedish Acceptance and Action Diabetes Questionnaire: A Rasch Analysis.
Background and purpose: The Acceptance and Action Diabetes Questionnaire (AADQ) is a tool for assessing the acceptance of thoughts and emotions related to diabetes in people living with the disease. This study aimed to examine the psychometric properties of the Swedish version of AADQ (Swe-AADQ) in a sample of adults with type 1 diabetes. Methods: To examine the psychometric properties of the Swe-AADQ, the Rasch model was used. Data for 120 individuals were included. Results: The Swe-AADQ showed an acceptable fit to the Rasch model. A sufficiently high value of the separation index indicated a capacity to distinguish between different levels of acceptance in the sample. The seven-point Likert scale was reduced to three categories suggesting an improvement in the ordering of the item thresholds. Conclusions: The Swe-AADQ possesses reasonable quality in terms of reliability and validity. However, there are some deficiencies regarding the categorization of the response rating that should be addressed.


Elephant growth hormone. Isolation and characterization.
Growth hormone has been purified to homogeneity from elephant pituitary glands. It has 191 amino acids with two disulfide bridges and a single tryptophan residue. The somatotropin activity is only 15% when compared with the bovine hormone in the radioreceptor binding assay. From circular dichroism spectra alpha-helical content of elephant growth hormone is estimated to be 50%. Difference absorption spectra of the hormone suggest the presence of a hydrogen bond between the single Trp and a carboxylate ion.


Tissue Parasites in HIV Infection.
The purpose of this review is to discuss the current knowledge of HIV and tissue parasite co-infection in the context of transmission enhancement, clinical characteristics, treatment, relapse, and clinical outcomes. The pathophysiology and clinical sequelae of tissue parasites in people living with HIV (PLWH) have been well described for only a handful of organisms, primarily protozoa such as malaria and leishmaniasis. Available published data indicate that the interactions between HIV and tissue parasites are highly variable depending on the infecting organism and the degree of host immunosuppression. Some tissue parasites, such as Schistosoma species, are known to facilitate the transmission of HIV. Conversely, uncontrolled HIV infection can lead to the earlier and more severe presentation of a variety of tissue parasites and can make treatment more challenging. Although much investigation remains to be done to better understand the interactions between consequences of HIV and tissue parasite co-infection, it is important to disseminate the current knowledge on this topic to health care providers in order to prevent, treat, and control infections in PLWH.


Seasonal and circadian patterns of myocardial infarction by coronary artery disease status and sex in the ACTION Registry-GWTG.
Myocardial infarction (MI) presentations are more common during winter months and morning hours. However, it is unknown whether MI with obstructive coronary artery disease (MI-CAD) and non-obstructive CAD (MINOCA) display similar patterns. We evaluated seasonal and circadian patterns of MI presentation by coronary artery disease (CAD) status and sex in patients with MI from 2007 to 2014 in the National Cardiovascular Data Registry (NCDR) Acute Coronary Treatment Intervention Outcomes Network (ACTION) Registry-Get With the Guidelines. Adult patients who underwent coronary angiography for MI were included. Patients with missing age, sex, or angiographic data, cocaine use, thrombolytic therapy prior to catheterization, or prior revascularization were excluded. Baseline demographics and characteristics of symptom onset, including season and time of day of presentation, were compared by CAD status and sex. Among 322,523 patients, 112,547 were female (35%); 18,918 had MINOCA (5.9%). There was no seasonal pattern of MI overall. However, both men and women with MINOCA presented more often in the summer and fall while MI-CAD presentations were equally distributed across seasons. The most common time of presentation was 8 am-2 pm regardless of CAD status or sex. A secondary peak in women with MINOCA during late afternoon hours was also identified. Seasonal variation of MI differed between MINOCA and MI-CAD, with a small increase in MINOCA incidence in the summer and fall. MINOCA and MI-CAD most commonly occurred in the morning, with a secondary peak in late afternoon in women with MINOCA. These differences in presentation may relate to underlying MI pathophysiology.


Assessing variability in chemical acute toxicity of unionid mussels: Influence of intra- and interlaboratory testing, life stage, and species.
The authors developed a toxicity database for unionid mussels to examine the extent of intra- and interlaboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the 2 life stages; and the variation in sensitivity among commonly tested mussels (Lampsilis siliquoidea, Utterbackia imbecillis, and Villosa iris), commonly tested cladocerans (Daphnia magna and Ceriodaphnia dubia), and fish (Oncorhynchus mykiss, Pimephales promelas, and Lepomis macrochirus). The results of these analyses indicate that intralaboratory variability for median effect concentrations (EC50) averaged about 2-fold for both life stages, whereas interlaboratory variability averaged 3.6-fold for juvenile mussels and 6.3-fold for glochidia. The EC50s for juveniles and glochidia were within a factor of 2 of each other for 50% of paired records across chemicals, with juveniles more sensitive than glochidia by more than 2-fold for 33% of the comparisons made between life stages. There was a high concurrence of sensitivity of commonly tested L. siliquoidea, U. imbecillis, and V. iris to that of other mussels. However, this concurrence decreased as the taxonomic distance of the commonly tested cladocerans and fish to mussels increased. The compiled mussel database and determination of data variability will advance risk assessments by including more robust species sensitivity distributions, interspecies correlation estimates, and availability of taxon-specific empirically derived application factors for risk assessment.


Neuronal activity reorganization in motor cortex for successful locomotion after a lesion in the ventrolateral thalamus.
Thalamic stroke leads to ataxia if the cerebellum-receiving ventrolateral thalamus (VL) is affected. The compensation mechanisms for this deficit are not well understood, particularly the roles that single neurons and specific neuronal subpopulations outside the thalamus play in recovery. The goal of this study was to clarify neuronal mechanisms of the motor cortex involved in mitigation of ataxia during locomotion when part of the VL is inactivated or lesioned. In freely ambulating cats, we recorded the activity of neurons in layer V of the motor cortex as the cats walked on a flat surface and horizontally placed ladder. We first reversibly inactivated ∼10% of the VL unilaterally using glutamatergic transmission antagonist CNQX and analyzed how the activity of motor cortex reorganized to support successful locomotion. We next lesioned 50%-75% of the VL bilaterally using kainic acid and analyzed how the activity of motor cortex reorganized when locomotion recovered. When a small part of the VL was inactivated, the discharge rates of motor cortex neurons decreased, but otherwise the activity was near normal, and the cats walked fairly well. Individual neurons retained their ability to respond to the demand for accuracy during ladder locomotion; however, most changed their response. When the VL was lesioned, the cat walked normally on the flat surface but was ataxic on the ladder for several days after lesion. When ladder locomotion normalized, neuronal discharge rates on the ladder were normal, and the shoulder-related group was preferentially active during the stride's swing phase.NEW & NOTEWORTHY This is the first analysis of reorganization of the activity of single neurons and subpopulations of neurons related to the shoulder, elbow, or wrist, as well as fast- and slow-conducting pyramidal tract neurons in the motor cortex of animals walking before and after inactivation or lesion in the thalamus. The results offer unique insights into the mechanisms of spontaneous recovery after thalamic stroke, potentially providing guidance for new strategies to alleviate locomotor deficits after stroke.


Additional vectors for PCR-based gene tagging in Saccharomyces cerevisiae and Schizosaccharomyces pombe using nourseothricin resistance.
The one-step PCR-mediated technique used for modification of chromosomal loci is a powerful tool for functional analysis in yeast. Both Saccharomyces cerevisiae and Schizosaccharomyces pombe are amenable to this technique. However, the scarce availability of selectable markers for Sz. pombe hampers the easy use of this technique in this species. Here, we describe the construction of new vectors deriving from the pFA6a family, which are suitable for tagging in both yeasts owing to the presence of a nourseothricin-resistance cassette. These plasmids allow various gene manipulations at chromosomal loci, viz. N- and C-terminal tagging with 3HA (haemagglutinin) or 13Myc epitopes, GST (glutathione S-transferase), 4TAP (tandem affinity purification) and several GFP (green fluorescent protein) isoforms. For N-terminal modifications, the use of different promoters allows constitutive (PADH1) or regulatable (PGAL1) promoters for S. cerevisiae and derivatives of Pnmt1 for Sz. pombe expression.


Aging-Related Catatonia with Reversible Dopamine Transporter Dysfunction in Females with Depressive Symptoms: A Case Series.
The authors describe five depressive patients with initially decreased striatal accumulation of dopamine transporter (DAT) single-photon emission computed tomography (SPECT), which improved in parallel with clinical symptoms. Patients who exhibited decreased striatal accumulation and recovery of DATSPECT were identified among patients with the symptoms of depression. Their clinical and neuroimaging data were reviewed. Five patients were identified. All patients were presenile or senile women who presented with catatonia subsequent to symptoms of depression that remitted with treatment. DAT-SPECT showed a decreased striatal accumulation in all patients, which increased after treatment. Two patients had met the diagnostic criteria of probable dementia with Lewy bodies (DLB), but no longer did so after their symptoms improved. Reversible DAT dysfunction observed in this study suggests that reversible impairment of dopaminergic transmission in the striatum partly underlies catatonia. Careful consideration should be given to diagnosing DLB in patients with decreased DAT-SPECT accumulation, especially when catatonia is present.


The expression of neural cell adhesion molecule and the microenvironment of pituitary neuroendocrine tumours.
The neural cell adhesion molecule (NCAM) has previously been studied in pituitary neuroendocrine tumours (PitNETs), but its role in tumour biology and aggressiveness remains controversial, and its relationship with the tumour microenvironment remains unknown. We aimed to characterise NCAM expression in PitNETs, to correlate this with clinico-pathological features, and to assess the role of various microenvironment components on NCAM expression. NCAM and immune cells were investigated by immunohistochemistry in 16 human non-functioning-PitNETs (NF-PitNETs) and eight somatotrophinomas, including macrophages (CD68, CD163, HLA-DR), cytotoxic (CD8) and T helper (CD4) lymphocytes, regulatory T cells (FOXP3), B cells (CD20), and neutrophils (neutrophil elastase). Five normal pituitaries were included for comparison. The cytokine secretome from these PitNETs and from PitNET-derived tumour-associated fibroblasts (TAFs) were assessed on culture supernatants using a multiplex immunoassay panel. There were no significant NCAM expression differences between PitNETs and normal pituitary, and no difference between types of pituitary tumours (NF-PitNETs vs. somatotrophinomas). There was no association between NCAM expression and different clinico-pathological features, including cavernous sinus invasion and Ki-67, nor with serum hormone levels. NCAM immunoreactivity correlated negatively with PitNET-derived CXCL10 (rho = -0.417; p = .042) and CX3CL1 (rho = -0.423; p = .040) levels. NCAM immunoreactivity was negatively correlated with TAF-derived fibroblast growth factor (FGF)-2 (rho = -0.632; p = .009), but not with other TAF-derived cytokines. Within the PitNET cohort, there were no correlations between NCAM immunoreactivity and immune infiltrates or ratios, although, within NF-PitNETs, NCAM expression was higher in tumours with more FOXP3+ cells. NCAM expression does not differ between PitNETs and normal pituitary, and does not appear to relate to tumour invasiveness or proliferation. However, our data suggest a possible role for cytokines in the modulation of NCAM expression in PitNETs, particularly CXCL10, CX3CL1 and FGF-2, but not for immune cell infiltrates.


Inhibition of the immunoproteasome modulates innate immunity to ameliorate muscle pathology of dysferlin-deficient BlAJ mice.
Muscle repair in dysferlinopathies is defective. Although macrophage (Mø)-rich infiltrates are prominent in damaged skeletal muscles of patients with dysferlinopathy, the contribution of the immune system to the disease pathology remains to be fully explored. Numbers of both pro-inflammatory M1 Mø and effector T cells are increased in muscle of dysferlin-deficient BlAJ mice. In addition, symptomatic BlAJ mice have increased muscle production of immunoproteasome. In vitro analyses using bone marrow-derived Mø of BlAJ mice show that immunoproteasome inhibition results in C3aR1 and C5aR1 downregulation and upregulation of M2-associated signaling. Administration of immunoproteasome inhibitor ONX-0914 to BlAJ mice rescues muscle function by reducing muscle infiltrates and fibro-adipogenesis. These findings reveal an important role of immunoproteasome in the progression of muscular dystrophy in BlAJ mouse and suggest that inhibition of immunoproteasome may produce therapeutic benefit in dysferlinopathy.


Accuracy of freehand external ventricular drain placement in patients after a large decompressive hemicraniectomy.
Our study aim is to evaluate the accuracy of freehand external ventricular drain (EVD) placement, without the use of adjuncts to placement, immediately following a large decompressive hemicraniectomy (DC). We performed a retrospective cohort analysis comparing patients who underwent freehand EVD placement immediately after a DC, to those who underwent freehand EVD placement without DC. Computed tomography (CT) studies were used to assess accuracy based on catheter tip location. Intracranial catheter length, pre- and post-operative Evan's Index, and midline shift pre- and post-operatively were analysed as separate variables in each group. A previously described grading system was used to assess the accuracy of free hand EVD placement. There were a total 110 patients overall; DC group, n = 50; non-DC group, n = 60. There was a significant reduction from pre-operative midline shift to post-operative midline shift in the DC group (9.13 vs 6.02 mm; p = 0.0064). There was no significant difference in accuracy between the two groups (p = 0.8917), and similar rates of Grade 1 - i.e. optimal - catheter tip location (DC = 78% vs non-DC = 81%) were found. All analysed variables comparing both Grade 1 subgroups (pre- and postoperative Evan's Index, and midline shift) showed significant differences between them. Mean catheter length in Grade 1 EVD placement showed a statistically significant difference between the DC and non-DC groups (63.78 vs 59.96 mm, respectively; p = 0.009). An EVD, after DC for traumatic and non-traumatic intracranial pathologies, can be accurately placed by freehand.


Outcome measures for primary Sjögren's syndrome.
Lymphocytic infiltration of different exocrine and non-exocrine epithelia is the pathological hallmark of primary Sjögren's syndrome, whereas involvement of salivary and lachrymal glands with the clinical counterpart of dry eye and dry mouth are the predominant features of the disease, together with fatigue and musculoskeletal pain. In addition, systemic manifestations, like arthritis, skin vasculitis, peripheral neuropathy, glomerulonephritis, may also be present in a consistent number of patients. As result, clinical features in SS can be divided into two facets: the benign subjective but disabling manifestations such as dryness, pain and fatigue, and the systemic manifestations. In the past decades, a core set of domains, which included sicca symptoms, objective measurements of tear and saliva production, fatigue, quality of life, disease activity and damage was indicated as essential for outcome assessment in this disorder. Afterwards, great efforts have been made to develop valid tools for the assessment of different domains. Specific questionnaires such as the Profile of Fatigue and Discomfort (PROFAD) and Sicca Symptoms Inventory (SSI) have been proposed as dedicated tools for the evaluation of patients symptoms, whereas different composite indexes have been suggested for the assessment of disease activity and damage. Some of these preliminary studies served as bases of an international project supported by EULAR, aimed at developing two consensus disease activity indexes: the EULAR Sjögren's Syndrome Patients Reported Index (ESSPRI), and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), a systemic activity index to assess systemic manifestations. A detailed and critical review of all these indexes is provided in this article. Both EULAR indexes showed, in recent studies, to be feasible, valid, and reliable instruments. After their final validation, which is currently in process, they could be used as consensus outcome criteria in therapeutic trials and in clinical practice.


Aging and defective lymphoid cell activation.
Activation of lymphocytes for proliferation is a crucial process in the immune response. Age-related deficiencies in this cellular response strongly correlate with deficiencies in the immune system response, with concomitant increase in disease severity and mortality. Defects associated with the transmission of the initial activation signal and with IL-2 production contribute to the depressed response, but defects in the IL-2 response mechanism also play important roles. A major factor in this area is the inability of the nuclei of these cells to respond to the intracellular factor ADR, which plays a crucial role in the initiation of DNA replication. These cells produce normal levels of ADR; thus, either the nuclei cannot bind ADR in a productive manner or the defect lies beyond the point of ADR binding, perhaps in one of the other proteins of the initiation complex. An interesting contrast to the age-related failure of nuclei to respond to ADR is the failure of neoplastic nuclei to respond to the ADR inhibitor. This inhibitor, found in the cytoplasm of quiescent cells, suppresses both the activation of quiescent nuclei by ADR and the ongoing DNA synthesis in isolated nuclei from activated cells. Nuclei from spontaneous proliferating cell lines were not affected by this inhibitor, which may be an important factor in the uncontrolled growth seen in neoplastic cells. The investigation of ADR has given hints that perhaps two of the fundamental questions in biology, namely why some cells don't proliferate and why some others won't stop proliferating, may be two sides of the same coin.


Alpha-1-antitrypsin and transferrin null alleles in the Portuguese population.
In a Portuguese family, a null allele was found in the Pi system. An apparent 'exclusion' of the mother was found to be due to the presence of null alleles in mother and child. A transferrin (Tf) null allele was found in a case of disputed paternity. The mother and putative father were heterozygous for Tf null alleles and the child was homozygous (TfQ0) and presented hypotransferrinemia.


Sleep-related erections: neural mechanisms and clinical significance.
Penile erections during rapid eye movement (REM) sleep are a robust physiologic phenomenon in all normal healthy males, irrespective of age. Given the involuntary nature of erections in sleep, sleep-related erection (SRE) testing has been used to differentiate psychogenic from organic impotence. The historical background of nocturnal penile tumescence, its current use, and common misconceptions of SRE testing are discussed. An animal model has been developed to study SRE mechanisms and has provided a new neural model regarding REM-related erectile control. The implications of these recent data on clinical SRE evaluation are presented. Finally, guidelines regarding SRE testing with polysomnography have not been available, contributing to a decline in formal SRE testing even though erections in sleep are commonly evaluated by urologists using home screening devices that do not record sleep. We propose a set of clinical indications when formal SRE evaluation in a sleep laboratory should be considered.


Three-way comparative study of endoscopic ultrasound-guided transmural gallbladder drainage using lumen-apposing metal stents versus endoscopic transpapillary drainage versus percutaneous cholecystostomy for gallbladder drainage in high-risk surgical patients with acute cholecystitis: clinical outcomes and success in an International, Multicenter Study.
Percutaneous cholecystostomy tube (PTGBD), endoscopic retrograde cholangiopancreatography with transpapillary gallbladder drainage (TP), and endoscopic ultrasound-guided transmural gallbladder drainage (EGBD) using lumen-apposing metal stents (LAMS) have been offered for gallbladder decompression for acute cholecystitis in high-risk surgical patients. Yet, there are limited data comparing these therapies. Our aim was to compare the safety and efficacy of EGBD to TP and PTGBD for gallbladder drainage. We retrospectively collected high-risk surgical patients from six centers with acute cholecystitis who underwent gallbladder drainage by EGBD, TP, or PTGBD. Data included technical success (gallbladder drainage), clinical success (acute cholecystitis resolution), adverse events (AE), and follow-up. From 2010 to 2016, 372 patients underwent gallbladder drainage, with 146 by PTGBD, 124 by TP, and 102 drained by EGBD. Technical (98% vs. 88% vs. 94%; p = 0.004) and Clinical (97% vs. 90% vs. 80%; p < 0.001) success rates were significantly higher with PTGBD and EGBD compared to TP. PTGBD group had statistically significantly higher number of complications as compared to EGBD and TP groups (2 0% vs. 2% vs. 5%; p = 0.01). Mean hospital stay in the EGBD group was significantly less than TP and PTGBD (16 vs. 18 vs. 19 days; p = 0.01), while additional surgical intervention was significantly higher in the PTGBD group compared to the EGBD and TP groups (49% vs. 4% vs. 11%; p < 0.0001). EGBD with LAMS is an effective and safer alternative to TP and PTGBD for treatment of patients with acute cholecystitis who cannot undergo surgery. EGBD with LAMS has significantly lower overall AEs, hospital stay, and unplanned admissions compared to PTGBD. ClinicalTrials.gov Identifier: NCT01522573.


Laparoscopic repair of incidentally found Spigelian hernia.
A Spigelian hernia is a rare type of hernia that occurs through a defect in the anterior abdominal wall adjacent to the linea semilunaris. Estimation of its incidence has been reported as 0.12% of all abdominal wall hernias. Traditionally, the method of repair has been an open approach. Herein, we discuss a series of laparoscopic repairs. Case series and review of the literature. Three patients are presented. All were evaluated and taken to surgery initially for a different disease process, and all were incidentally found to have a spigelian hernia. These patients underwent laparoscopic repair of their hernias; 2 were repaired intraperitoneally and one was repaired totally extraperitoneally. Two patients initially underwent a mesh repair, while the third had an attempted primary repair. There is evidence that supports the use of laparoscopy for both diagnosis and repair of spigelian hernias. There are also reports of successful repairs both primarily and with mesh. In our experience with the preceding 3 patients, we found that laparoscopic repair of incidentally discovered spigelian hernias is a viable option, and we also found that implantation of mesh, when possible, resulted in satisfactory results and no recurrence.


Intelligent double-layer polymers based on carboxymethyl cellulose-cellulose nanocrystals film and poly(lactic acid)-Viola odorata petal anthocyanins nanofibers to monitor food freshness.
The present study was conducted with the aim of fabricating smart bilayer polymers based on carboxymethyl cellulose-cellulose nanocrystals film and poly(lactic acid)-Viola odorata extract nanofibers (CMC-CNC and PLA-VOE) for freshness monitoring of Pacific white shrimps, minced lamb meat, chicken fillets, and rainbow trout fillets, during refrigerated storage conditions. The fabricated indicators based on CMC-PLA-VOE 5%, CMC-CNC 1%-PLA-VOE 5%, and CMC-CNC 3%-PLA-VOE 5% presented remarkable color changes in pH 1-12 buffer solutions, including red at pH 1-6, violet at pH 7-8, green at pH 9-10, and brown at pH 11-12. Significantly lower water vapor permeability and oxygen transmission rate of prepared polymers were found in comparison with the control groups (P < 0.05). Regarding the monitoring of food samples in real-time, the samples spoiled after 3 days, evidenced by total viable count, psychrotrophic bacterial count, total volatile basic nitrogen, and pH values of 7.17-7.54 log CFU/g, 5.68-6.23 log CFU/g, 25.14-28.12 mg N/100 g, and 7.10-7.66, respectively. Meanwhile, the noticeable color change of prepared indicators from white to violet (day 3) and finally dark violet (day 7) was observed, indicating a potential application in intelligent packaging for real-time control of the freshness of perishable food samples.