Natural killer cell infection and inactivation in vitro by the human immunodeficiency virus.
Cytolytic activity of human mononuclear peripheral blood leukocytes from healthy donors, cultured in interleukin-2 conditioned medium, was abrogated by in vitro infection with the lymphadenopathy associated virus (LAV) isolate of the human immunodeficiency virus (HIV). Although viral antigens are not expressed in cultured cells until 14 days postinfection, cytolytic activity was lost as early as 3 days after infection. Loss of cytolytic function was not a result of the release of suppressive factors from either infected cells or uninfected CEM cells since supernatants from neither infected cultures nor CEM cell cultures had any inhibitory effects on the function of uninfected cells. Cultured lymphocytes expressing Leu 11b were also shown to express HIV antigens via immunofluorescence after 14 days in culture. These results suggest that natural killer (NK) cells, as defined by expression of Leu 11b, were infected by HIV in vitro and the loss of lytic function was likely a direct consequence of that infection.


Paroxysmal ataxia and dysarthria in multiple sclerosis.
Paroxysmal ataxia and dysarthria are part of the spectrum of transient neurological disturbances that can be frequently encountered in multiple sclerosis (MS). Prompt recognition of these symptoms is important because they can be the only manifestation of a MS relapse and symptomatic therapy is often beneficial. We report a patient who developed paroxysmal ataxia and dysarthria, documented by video imaging, while he was recovering from a MS relapse. Treatment with carbamazepine resulted in the complete reversal of the paroxysmal ataxia and dysarthria.


Oligotide, a new single-stranded oligodeoxyribonucleotide, preserves postsynaptic beta-adrenergic and cholinergic receptor functions in rabbit hearts after acute infarction.
Acute myocardial infarction was induced in New Zealand male albino rabbits. 3 days after surgery, the mortality rate and plasma CPK activity were reduced by 64% and 66% respectively by intravenous infusion of Oligotide (32 mg/kg/h for 6h), a single-stranded oligodeoxyribonucleotide of mammalian origin. Perfused hearts, obtained from Oligotide-treated rabbits 3 days after surgery, showed a strength of contraction in the range of that of hearts of sham-operated animals and an ameliorated postsynaptic beta-adrenergic and cholinergic receptor function. In addition, in these hearts, "ex vivo" treatment with Oligotide resulted in almost complete preservation of both adrenergic and cholinergic responses to their specific agonists. These data suggest that Oligotide by protecting the hearts from the ischemic damage and possibly by restricting left ventricular tissue necrosis may have normalized the biological responses of this organ to isoproterenol and preserved the integrity of coronary endothelial-dependent relaxant function.


Intrinsic array structure is neither necessary nor sufficient for nonegocentric coding of spatial layouts.
Mou and McNamara (2002) have recently theorized that nonegocentric reference frames (viz., intrinsic reference frames, based on the spatial structure of a configuration of objects) are used to organize spatial relationships in memory. The theory has not made claims about whether the intrinsic structure of a stimulus array is necessary or sufficient for such nonegocentric coding. We demonstrate that salient intrinsic axes in a layout of objects are neither necessary nor sufficient for people to use a nonegocentric reference frame in organizing spatial memory. In Experiment 1, participants were successfully instructed to adopt a nonegocentric preferred direction in memory for an array of objects with no salient intrinsic reference axes. In Experiment 2, with no instructions, participants adopted an egocentric preferred direction for an array with a salient intrinsic axis. These results suggest that physically salient array structure exerts a minimal influence in the coding of spatial memory through nonegocentric reference frames.


Consensus standards and performance indicators for prevention and control of healthcare-associated infection in Europe.
Healthcare-associated infection (HCAI) and related problems of antimicrobial resistance (AMR) place a considerable burden on healthcare delivery, patients, their families and carers, and the economy. Once considered a low priority, they are now recognized globally as major patient safety issues. The European Union's Directorate General for Health and Consumer Protection released a public consultation on strategies for improving patient safety by the prevention and control of HCAI, and increased standards of antimicrobial stewardship. They also specified that the 'Improving Patient Safety in Europe' research project they had funded would develop consensus standards and related performance indicators (SPIs) for the prevention and control of HCAI and AMR. This article describes how consensus was reached between 29 participating European countries, the detailed SPIs, and a reduced set of indicators ('13+13') that could be used internationally and nationally to stimulate and review improvement in HCAI prevention and control, and antimicrobial stewardship activities.


Comprehensive examination of conventional and innovative body fluid identification approaches and DNA profiling of laundered blood- and saliva-stained pieces of cloths.
Body fluids like blood and saliva are commonly encountered during investigations of high volume crimes like homicides. The identification of the cellular origin and the composition of the trace can link suspects or victims to a certain crime scene and provide a probative value for criminal investigations. To erase all traces from the crime scene, perpetrators often wash away their traces. Characteristically, items that show exposed stains like blood are commonly cleaned or laundered to free them from potential visible leftovers. Mostly, investigators do not delegate the DNA analysis of laundered items. However, some studies have already revealed that items can still be used for DNA analysis even after they have been laundered. Nonetheless, a systematical evaluation of laundered blood and saliva traces that provides a comparison of different established and newly developed methods for body fluid identification (BFI) is still missing. Herein, we present the results of a comprehensive study of laundered blood- and saliva-stained pieces of cloths that were applied to a broad range of methods for BFI including conventional approaches as well as molecular mRNA profiling. The study included the evaluation of cellular origin as well as DNA profiling of blood- and saliva-stained (synthetic fiber and cotton) pieces of cloths, which have been washed at various washing temperatures for one or multiple times. Our experiments demonstrate that, while STR profiling seems to be sufficiently sensitive for the individualization of laundered items, there is a lack of approaches for BFI with the same sensitivity and specificity allowing to characterize the cellular origin of challenging, particularly laundered, blood and saliva samples.


Role of Psychedelics in Treatment-Resistant Depression.
There is increasing interest in exploring the therapeutic potential of psychedelics in treatment-resistant depression (TRD). Classic psychedelics (such as psilocybin, LSD, ayahuasca/DMT), and atypical psychedelics (such as ketamine) have been studied in TRD. The evidence for the classic psychedelics TRD is limited at the present time; early studies however show promising results. There is also recognition that psychedelic research may be subject to a "hype bubble" at the present time. Future studies focused on delineating necessary ingredients of psychedelic treatments and the neurobiological basis of their effects, will help pave the way for the clinical use of these compounds.


Safety and antitumor effect of oncolytic and helper-dependent adenoviruses expressing interleukin-12 variants in a hamster pancreatic cancer model.
Gene transfer of potent immunostimulatory cytokines such as interleukin-12 (IL-12) is a potential treatment for advanced cancer. Different vectors and IL-12 modifications have been developed to avoid side effects associated with high serum levels of the cytokine, while preserving its antitumor properties. Here we have evaluated two alternative strategies using the Syrian hamster as a model for pancreatic cancer metastatic to the liver. Local administration of an oncolytic adenovirus (OAV) expressing a single-chain version of IL-12 caused transient, very intense elevations of IL-12 in serum, resulting in severe toxicity at sub-therapeutic doses. Anchoring IL-12 to the membrane of infected cells by fusion with the transmembrane domain of CD4 reduced systemic exposure to IL-12 and increased the tolerance to the OAV. However, only a modest increase in the therapeutic range was achieved because antitumor potency was also reduced. In contrast, systemic administration of a helper-dependent adenoviral vector (HDAd) equipped with a Mifepristone-inducible expression system allowed sustained and controlled IL-12 production from the liver. This treatment was well tolerated and inhibited the progression of hepatic metastases. We conclude that HDAds are safer than OAVs for the delivery of IL-12, and are promising vectors for immunogene therapy approaches against pancreatic cancer.


Partial cardiopulmonary bypass, hypothermic circulatory arrest, and posterolateral exposure for thoracic aortic aneurysm operation.
Partial cardiopulmonary bypass, profound hypothermia, and circulatory arrest were used in the treatment of 25 patients with thoracic aortic aneurysms exposed through left posterolateral incisions. Indications included aortic clamp laceration (4 patients), pulmonary artery tear (1), treatment of ruptured aneurysm without clamping (5), right-sided arch (2), exposure of proximal aorta in a patient with a large aneurysm (1), inability to expose the proximal aorta for clamping (3), to permit removal of both arch and distal aorta (4), and to avoid distal arch clamping because of atheromatous disease (5). Aortic segments ranging from the upper descending thoracic aorta to most of the aorta were replaced, with early survival in 21 patients. Cerebral protection was satisfactory.


Endothelium-dependent hyperpolarization of smooth muscle cells in rabbit femoral arteries is not mediated by EDRF (nitric oxide).
Acetylcholine elicits an endothelium-dependent hyperpolarization of vascular smooth muscle cells. The experiments reported here tested the hypothesis that this hyperpolarization is mediated by the endothelium-derived relaxant factor (EDRF) identified as nitric oxide. Membrane potential was recorded with standard glass microelectrodes in smooth muscle cells in segments of rabbit femoral arteries. In endothelium-intact vessels, smooth muscle cells (resting potential: -67.0 +/- 1.3 mV) hyperpolarized significantly (P less than 0.001) by 5.7 +/- 0.9 mV in response to acetylcholine (1 microM). Inhibition of EDRF, either in the presence of hemoglobin or by pretreatment with gossypol, attenuated the relaxation elicited by acetylcholine in endothelium-intact segments precontracted with 0.1 microM noradrenaline but had no significant effect on either the control membrane potential (-62.2 +/- 1.9 mV and -68.5 +/- 2.1 mV, respectively) or the hyperpolarization in response to acetylcholine (5.0 +/- 1.6 mV and 5.8 +/- 1.6 mV, respectively). In contrast, in vessel segments with the endothelium removed, the hyperpolarization in response to acetylcholine was abolished although the control membrane potential (-68.0 +/- 5.1 mV) was not significantly different from that in endothelium-intact vessels. Sodium nitroprusside, an endothelium-dependent vasodilator and exogenous analog of EDRF, also had no significant effect on membrane potential. The lack of response to acetylcholine was not merely the result of nonspecific damage to the smooth muscle cells: vessel segments without endothelium were still able to hyperpolarize in response to various other vasodilators. These results suggest that the endothelium-dependent hyperpolarization of vascular smooth muscle cells in response to acetylcholine is not mediated by EDRF.


Access to healthcare and prevalence of anxiety and depression in persons with epilepsy during the COVID-19 pandemic: A multicountry online survey.
The objective of this study was to assess access to healthcare and to estimate the prevalence of depression and anxiety among persons with epilepsy (PWE) during the ongoing coronavirus disease 2019 (COVID-19) pandemic. We conducted a multicountry online survey among PWE. Persons with epilepsy were invited to participate through various social media channels. The Hospital Anxiety and Depression Scale (HADS) and 9-item Patient Health Questionnaire (PHQ-9) scale were used to score anxiety and depression. Logistic regression modeling was used to investigate factors associated with anxiety and depression. Three hundred ninety-nine PWE were included (mean age: 38.22 ± 12.09 years), the majority were female (80.2%) and living in high-income countries (83.2%). Two hundred three PWE reported symptoms of a cold since January 2020. Nine (25%) of the 36 PWE tested for COVID were positive. A total of 72 PWE (19.6%) reported problems to obtain antiseizure medication (ASM), which in 25% of cases was directly COVID-related. Of the 399 PWE, 201 (50.4%) screened positive for anxiety according to the HADS; 159 (39.8%) and 187 (46.9%) PWE screened positive for depression based on the HADS and PHQ-9 scale, respectively. Female gender and financial problems were associated with both depression and anxiety. A planned follow-up consultation with the treating physician was associated with a lower risk of depression, whereas difficulties to access ASM treatment increased the odds of depression. In 65/137 (47.4%) PWE with a planned follow-up visit with the treating physician, this consultation was canceled. Innovative approaches are needed to ensure continuity in access to ASM treatment. Healthcare workers should ensure continued follow-up, either through inperson or telehealth appointments, to timely identify symptoms of anxiety and depression and act accordingly.


Lessons learned implementing a regional health information exchange in Geneva as a pilot for the Swiss national eHealth strategy.
It took more than ten years from the initial mandate to the first implementation of e-toile, the Geneva health information exchange. Although most actors quickly agreed on the goals and potential benefits of such a system, obstacles were many, and mostly non-technical. The transparency resulting from a streamlined exchange of information may improve the continuity, quality and efficiency of care, while, at the same time, reveal and challenge habits and practices of care professionals and of citizens. This tension must be understood, and trust must be fostered amongst stakeholders. In our experience, key enablers were the collaborative elaboration and negotiation of an eHealth law, the definition of an eHealth strategy, as well as the involuntary increased financial pressure on all healthcare stakeholders. Nevertheless, and even though it is often cited as a successful model, the Swiss health system, being highly fragmented and based on a complex interplay of private and public stakeholders, is not as conducive to the deployment of eHealth systems as most other developed countries.


The influence of maternal glucose metabolism on fetal growth, development and morbidity in 917 singleton pregnancies in nondiabetic women.
To study the effects on the fetus of variations in maternal glucose tolerance, a 25 g rapid intravenous glucose tolerance test was performed at or about 32 weeks gestation in 917 randomly selected nondiabetic women with singleton pregnancies. The results were withheld from the patients and their obstetricians and paediatricians, and no treatment or advice was offered. Fasting plasma glucose and indices of glucose disposal (including a new index which we have termed "summed glucose") were distributed unimodally, with no evidence of a separate pathological group towards the diabetic end of the distributions. Significant associations were found between maternal glucose metabolism and various measures of neonatal nutrition and morbidity, including the incidence of congenital malformations and morbidity related to asphyxia, suggesting that variations within the normal range in maternal glucose metabolism can influence growth and development in the fetus. These relationships were continuous throughout the range of maternal glucose tolerance and were not of predictive value in individual cases.


Degradation of atrazine by electroactivation of persulfate using FeCuO@C modified composite cathode: Synergistic activation mechanism.
In sulfate radical-based advanced oxidation processes (SR-AOPs), high-efficiency and perdurable materials have drawn considerable interest for use as cathodes, which can effectively degrade refractory organic contaminants through the synergistic electro-activation and transition metal activation of persulfate (PS). Here, the FeCuO@C modified composite cathode (FeCuO@C/AGF) was synthesized via the solvothermal and thermal treatment method based on the CuFe-MOF-74 structure, and the electro-activation PS process (EC/FeCuO@C/AGF/PS) was developed to effectively remove atrazine (ATZ). The surface morphology, electrochemical characteristics, chemical composition, crystal structure, and electrode surface wettability of FeCuO@C/AGF were investigated. It was found that the proposed EC/FeCuO@C/AGF/PS process can successfully remove 100% of ATZ in 20 min at a low current density (2 mA cm-2) and a low PS concentration (0.4 mM), and PS is successfully activated by combining the electrical and transition metal synergistic activation. The FeCuO@C/AGF cathode exhibits outstanding catalytic functionality over a broad pH range (2-9) and remains stable over five successive cycles. Additionally, the active species involved in the reaction as well as the potential ATZ degradation reaction mechanisms and pathways are discussed. Electrochemical oxidation is a process in which both radicals (SO4·-, ·OH, and O2·-) and non-radical (1O2) participate in the degradation of ATZ. The intermediates of the ATZ degradation process were studied upon the toxicity changing, and the toxicity of the intermediates was found to be reduced during degradation. These results present a novel approach toward the establishment of an effective and reliable electrode in SR-AOPs that can efficiently treat pesticide wastewater.


The role of morphological changes in algae adaptation to nutrient stress at the single-cell level.
Individual cell heterogeneity within a population can be critical to its peculiar function and fate. Conventional algal cell-based assays mainly analyze the average responses from a population of algal cells. Therefore, the mechanisms through which changes in population characteristics are driven by the behavior of single algal cells are still not well understood. Algal cells may modulate their physiology and metabolism by changing their morphology in response to environmental stress. In this study, an algal single-cell culture and analysis system was developed to investigate the potential role of morphological changes by algal cells during adaptation to nutrient stress based on a microwell array chip. The surface-to-volume ratio of Microcystis aeruginosa (M. aeruginosa) and the volume of Scenedesmus obliquus (S. obliquus) significantly increased with increasing culture time under nutrient stress. The eccentricity of M. aeruginosa and S. obliquus gradually increased and decreased, respectively, with increasing culture time, indicating that the morphology of M. aeruginosa and S. obliquus became increasingly irregular and regular, respectively, under nutrient stress. There were significant correlations between the morphological characteristics and physiological characteristics of M. aeruginosa and S. obliquus under nutrient stress. In M. aeruginosa, an increased surface-to-volume ratio facilitated a high specific fluorescence intensity, specific Raman intensity, and maximum electron transport rate. In S. obliquus, increased cell volume enhanced nutrient absorption, which facilitated a higher specific growth rate. M. aeruginosa and S. obliquus adopted different adaptation strategies in response to nutrient stress based on morphological changes. These findings facilitate the development of management strategies for controlling harmful cyanobacterial blooms.


Comparison of nominal recall (standard) and multiple-choice methods for administration of WISC-R information subtest: a preliminary study indicating a learning effect of multiple-choice testing.
The Wechsler Intelligence Scale for Children--Revised (WISC--R) Information subtest was administered to learning disabled children using two methods of administration, the standard (recall) method and a multiple-choice format. Those children who were tested first with the multiple-choice format and subsequently with the standard format did better on the standard format than expected. This preliminary study suggests a learning effect of such multiple-choice testing and the desirability of further research being undertaken.


Characteristics of infant urolithiasis: A single center experience in western Turkey.
Urolithiasis (UL) in infancy has different incidence, etiology, presentation and course compared to UL in childhood and in adults. We evaluated the clinical, radiological, metabolic factors and course of infant UL in western Turkey. Medical records of the infants between 1 and 12 months of age with a diagnosis of UL were reviewed retrospectively for gender, gestational age, age at diagnosis, presenting symptoms, past medical history, parental consanguinity, family history of UL, urinary tract abnormalities, urinary tract infections, localization-size-number of stones, course of stones, treatment modality of UL (medical vs surgical) and follow up duration. Patients were grouped as those who did not require surgical intervention (Group 1) and those who underwent any kind of stone surgery (Group 2). Both groups were compared for the study parameters. There were 80 infants (48 males) with a mean age of 6.0 ± 2.9 months at diagnosis. Mean follow-up duration was 29.7 ± 23.1 months. Two thirds of the patients presented with symptoms/signs not directly related to urinary system. Predisposing factors included metabolic abnormalities in 24 (30%) patients and urinary tract malformations in 9 (11%) patients. Group 1 (n = 58) and Group 2 (n = 22) were not different with respect to the study parameters except for the larger stone size and higher rate of hyperuricosuria in Group 2. Stone size of 4.5 mm has a 72.7% sensitivity and 74.1% specificity for predicting surgical intervention. Infants treated medically and those followed by hydration only did not differ for regression rate of stones and for requirement for surgical intervention. However, metabolic abnormalities were significantly higher in medically treated infants. Every infant with urolithiasis should be evaluated for risk factors. Modification of such predisposing factors when possible may mitigate the notably high recurrence rate of UL in children. Increased awareness of infant UL may allow for earlier detection, improved evaluation and follow up, and may thereby decrease the morbidity of the disease.


Effectiveness of registered nurses on patient outcomes in primary care: a systematic review.
Globally, registered nurses (RNs) are increasingly working in primary care interdisciplinary teams. Although existing literature provides some information about the contributions of RNs towards outcomes of care, further evidence on RN workforce contributions, specifically towards patient-level outcomes, is needed. This study synthesized evidence regarding the effectiveness of RNs on patient outcomes in primary care. A systematic review was conducted in accordance with Joanna Briggs Institute methodology. A comprehensive search of databases (CINAHL, MEDLINE Complete, PsycINFO, Embase) was performed using applicable subject headings and keywords. Additional literature was identified through grey literature searches (ProQuest Dissertations and Theses, MedNar, Google Scholar, websites, reference lists of included articles). Quantitative studies measuring the effectiveness of a RN-led intervention (i.e., any care/activity performed by a primary care RN) that reported related outcomes were included. Articles were screened independently by two researchers and assessed for bias using the Integrated Quality Criteria for Review of Multiple Study Designs tool. A narrative synthesis was undertaken due to the heterogeneity in study designs, RN-led interventions, and outcome measures across included studies. Forty-six patient outcomes were identified across 23 studies. Outcomes were categorized in accordance with the PaRIS Conceptual Framework (patient-reported experience measures, patient-reported outcome measures, health behaviours) and an additional category added by the research team (biomarkers). Primary care RN-led interventions resulted in improvements within each outcome category, specifically with respect to weight loss, pelvic floor muscle strength and endurance, blood pressure and glycemic control, exercise self-efficacy, social activity, improved diet and physical activity levels, and reduced tobacco use. Patients reported high levels of satisfaction with RN-led care. This review provides evidence regarding the effectiveness of RNs on patient outcomes in primary care, specifically with respect to satisfaction, enablement, quality of life, self-efficacy, and improvements in health behaviours. Ongoing evaluation that accounts for primary care RNs' unique scope of practice and emphasizes the patient experience is necessary to optimize the delivery of patient-centered primary care. PROSPERO: International Prospective Register of Systematic Reviews. 2018. ID=CRD42 018090767 .


Prostate tissue texture feature extraction for suspicious regions identification on TRUS images.
In this work, two different approaches are proposed for region of interest (ROI) segmentation using transrectal ultrasound (TRUS) images. The two methods aim to extract informative features that are able to characterize suspicious regions in the TRUS images. Both proposed methods are based on multi-resolution analysis that is characterized by its high localization in both the frequency and the spatial domains. Being highly localized in both domains, the proposed methods are expected to accurately identify the suspicious ROIs. On one hand, the first method depends on a Gabor filter that captures the high frequency changes in the image regions. On the other hand, the second method depends on classifying the wavelet coefficients of the image. It is shown in this paper that both methods reveal details in the ROIs which correlate with their pathological representations. It was found that there is a good match between the regions identified using the two methods, a result that supports the ability of each of the proposed methods to mimic the radiologist's decision in identifying suspicious regions. Studying two ROI segmentation methods is important since the only available dataset is the radiologist's suspicious regions, and there is a need to support the results obtained by either one of the proposed methods. This work is mainly a preliminary proof of concept study that will ultimately be expanded to a larger scale study whose aim will be introducing an assisting tool to help the radiologist identify the suspicious regions.


Hands-on defibrillation: an analysis of electrical current flow through rescuers in direct contact with patients during biphasic external defibrillation.
Brief interruptions in chest compressions reduce the efficacy of resuscitation from cardiac arrest. Interruptions of this type are inevitable during hands-off periods for shock delivery to treat ventricular tachyarrhythmias. The safety of a rescuer remaining in contact with a patient being shocked with modern defibrillation equipment has not been investigated. This study measured the leakage voltage and current through mock rescuers while they were compressing the chests of 43 patients receiving external biphasic shocks. During the shock, the rescuer's gloved hand was pressed onto the skin of the patient's anterior chest. To simulate the worst case of an inadvertent return current pathway, a skin electrode on the rescuers thigh was connected to an electrode on the patient's shoulder. In no cases were shocks perceptible to the rescuer. Peak potential differences between the rescuer's wrist and thigh ranged from 0.28 to 14 V (mean 5.8+/-5.8 V). The average leakage current flowing through the rescuer's body for each phase of the shock waveform was 283+/-140 microA (range 18.9 to 907 microA). This was below several recommended safety standards for leakage current. Rescuers performing chest compressions during biphasic external defibrillation are exposed to low levels of leakage current. The present findings support the feasibility of uninterrupted chest compressions during shock delivery, which may enhance the efficacy of defibrillation and cardiocerebral resuscitation.


Energetics of surface confined ferritin during iron loading.
We report on the first quantitative picture on how iron loading inside ferritin molecules occurs when they are self-assembled onto solid surfaces. Recombinant human ferritin H-chain with ferroxidase activity was adsorbed onto microcantilever beams to form a stable close-packed thin film. The obtained nanomechanical system was used to track in real time the energetics of inter-ferritin surface interactions during incubation with Fe(II) for iron loading. We observed that iron loading is accompanied by increasing attractive in-plane inter-ferritin interactions able to perform a maximum surface work of 6.0±1.5mJ/m(2), corresponding to a surface energy variation per ferritin of about 40kbT. Unique to this protein surface transformation, part of the surface work is exerted by the attractive electrostatic forces arising among the new born nanosized iron cores inside the ferritin shells. The remaining work comes from subtle action of steric, bridging and depletion forces. These findings are of fundamental interest and add important information for the rational development of ferritin nanotechnology.


Early brain amyloidosis in APP/PS1 mice with serum insulin-like growth factor-I deficiency.
The influence of insulin-like growth factor I (IGF-I) on the progression of Alzheimer's disease (AD) is discussed controversially. To help clarify the role of this circulating neurotrophic factor in brain amyloidosis, the major pathological trait in AD, we analyzed plaque formation in a mouse model of AD transgenic for human APP and PS1 mutations with reduced serum IGF-I levels (LIDAD mice). We found that brain amyloidosis in LIDAD mice appeared earlier than in AD mice, at 2 months of age, while attained comparable levels at 6 months. In parallel, early microgliosis was observed in LIDAD mice also at 2 months and remained exacerbated at 6 months. Collectively, these observations suggest a role of serum IGF-I in delaying early brain amyloidosis.


[The level of aberrant lymphocytes in the blood of rats and duration of survival after radionuclide incorporation].
There is a positive correlation between the number of aberrant lymphocytes in the experimental rat blood, 24 h following the administration of 45Ca, 131I, 131I together with 90Sr, and 45Ca together with 137Cs, and the life span of exposed animals. It is suggested that the cytogenetic index should be used in the prognosis of the radionuclide-induced life span shortening.


Towards the CSNK2 phosphoproteome - With lessons from the COVID-19 pandemic to revealing the secrets of CSNK2 and its promise as a therapeutic target.
Dramatic advances in phosphoproteomics and the development of a selective chemical probe have presented new opportunities for revealing the cellular landscape of substrates for CSNK2 (formerly known as CK2 or casein kinase II). In addition to deciphering the role(s) of CSNK2 in physiology and pathophysiology, the CSNK2 phosphoproteome offers the promise of instructing the development of CSNK2-targeted therapy.


Assembly of the active center of organophosphorus hydrolase in metal-organic frameworks via rational combination of functional ligands.
Different from popular mimics of bimetallic nuclear centers bridged by a hydroxide, a total coordination sphere of the active center of organophosphorus hydrolase was assembled in metal-organic frameworks by rational design and combination of ligands, which resulted in efficient destruction of nerve agent stimulants without a base as a co-catalyst.


SIDS--a developmental neurological perspective.
Most SIDS deaths occur between 2 and 4 months of age. Neural transformations may be important in SIDS. Evidence of delayed myelination has been found in SIDS victims. However a simple neuro-developmental model is insufficient to explain SIDS. The age of death profile is reportedly similar for pre-term and full-term SIDS victims. Another developmental change is that IgG levels are lowest when SIDS risk peaks, and there is data linking SIDS and infections. Prone position may also increase risk. While a developmental model emphasizing neural transformation is useful, other factors affect risk also.


The origin of sensory nerve fibers that innervate the submandibular salivary gland in the rat.
The origin of sensory nerves that innervate the submandibular salivary gland was investigated in the rat. After application of wheat germ agglutinin-horseradish peroxidase to the cut endings of the sympathetic and parasympathetic nerve branches at the hilus of the gland, labeled cells were mainly found in the dorsal root ganglia and the trigeminal ganglion, respectively. The labeled neurons in these ganglia were of various sizes compared to unlabeled neurons, suggesting that the sensory nerves of the gland conduct various modalities of sensory information.


Role of cellular superoxide dismutase against reactive oxygen metabolite-induced cell damage in cultured rat hepatocytes.
Reactive oxygen metabolites have been reported to be important in the pathogenesis of ischemia/reperfusion-induced and alcohol- and drug-induced liver injuries. We investigated the role of superoxide dismutase, cellular and extracellular, in preventing reactive oxygen metabolite-induced cytotoxicity in cultured rate hepatocytes. Cells were exposed to reactive oxygen metabolites enzymatically generated by hypoxanthine-xanthine oxidase. Cytotoxicity was quantified by measuring 51Cr release from prelabeled cells and lactate dehydrogenase release. Reactive oxygen metabolites caused dose-dependent cytotoxicity. Good correlation was found between the values for 51Cr and lactate dehydrogenase release. Reactive oxygen metabolite-induced cell damage was reduced by catalase but not by superoxide dismutase. Cellular superoxide dismutase and catalase activities were not increased after incubation with exogenous superoxide dismutase and catalase for up to 5 hr. Pretreatment with diethyldithiocarbamate inhibited cellular superoxide dismutase activity without inhibiting other antioxidants such as catalase, glutathione, glutathione reductase and glutathione peroxidase and sensitized cells to reactive oxygen metabolite-induced cytotoxicity. We conclude that hydrogen peroxide is an important mediator in hypoxanthine-xanthine oxidase-induced cell damage and that superoxide dismutase plays a critical role in cellular antioxidant defenses against hypoxanthine-xanthine oxidase-induced cytotoxicity in cultured rat hepatocytes in vitro.


The Hubbard tank as an adjunct to drainage in overwhelming intra-abdominal sepsis.
Open drainage of the peritoneal cavity for severe intra-abdominal sepsis has been gaining popularity. We had a patient whose overwhelming intra-abdominal infection did not respond to open drainage but was controlled by frequent immersion in a Hubbard tank. Use of the Hubbard tank should be considered in patients with uncontrolled intra-abdominal infection refractory to standard therapy.


Low-carbohydrate diet versus caloric restriction: effects on weight loss, hormones, and colon tumor growth in obese mice.
Our objective was to compare the effects of a low-carbohydrate diet to a high-carbohydrate/calorie-restricted diet on weight loss, hormones, and transplanted colon tumor growth. Eighty male C57BL/6 mice consumed a diet-induced obesity regimen (DIO) ad libitum for 7 weeks. From Weeks 8 to 14, the mice consumed a 1) DIO diet ad libitum (HF); 2) low-carbohydrate diet ad libitum (LC); 3) high-carbohydrate diet ad libitum (HC); or 4) HC calorie restricted diet (HC-CR). MC38 cells were injected at Week 15. At the time of injection, the HC-CR group displayed the lowest body weight (25.5 +/- 0.57 g), serum insulin-like growth factor I (IGF-I; 135 +/- 56.0 ng/ml), and leptin (1.0 +/- 0.3 ng/ml) levels. This group also exhibited the longest time to palpable tumor (20.1 +/- 0.9 days). Compared to the HF group, the HC group exhibited lower body weight (39.4 +/- 1.4 vs. 32.9 +/- 0.7 g, respectively), IGF-I (604 +/- 44.2 vs. 243.4 +/- 88.9 ng/ml, respectively), and leptin (15.6 +/- 2.2 vs. 7.0 +/- 0.7 ng/ml, respectively) levels but similar tumor growth. IGF-I levels were lower in the LC group (320.0 +/- 39.9 ng/ml) than the HF group, but tumor growth did not differ. These data suggest LC diets do not slow colon tumor growth in obese mice.


Let the pigeon drive the bus: pigeons can plan future routes in a room.
The task of determining an optimal route to several locations is called the traveling salesperson problem (TSP). The TSP has been used recently to examine spatial cognition in humans and non-human animals. It remains unclear whether or not the decision process of animals other than non-human primates utilizes rigid rule-based heuristics, or whether non-human animals are able to flexibly 'plan' future routes/behavior based on their knowledge of multiple locations. We presented pigeons in a One-way and Round-Trip group with TSPs that included two or three destinations (feeders) in a laboratory environment. The pigeons departed a start location, traveled to each feeder once before returning to a final destination. Pigeons weighed the proximity of the next location heavily, but appeared to plan ahead multiple steps when the travel costs for inefficient behavior appeared to increase. The results provide clear and strong evidence that animals other than primates are capable of planning sophisticated travel routes.


Role of AKT and ERK pathways in controlling sensitivity to ionizing radiation and adaptive response induced by low-dose radiation in human immune cells.
Despite many studies of the effect of ionizing radiation, biological mechanisms of action might differ greatly depend on dose, dose rate, and cell type. This study was performed to explore the effects of low- and high-dose radiation in human immune cell lines. We examined cell sensitivity after irradiation with 0.05, 0.1, or 2Gy in two normal cell lines and three tumor cell lines. Low-dose radiation of 0.05 and 0.1Gy had no effect on cell survival in any tested cell line, with the exception of IM-9 cells, whose viability was transiently increased. However, IM-9 and C1R-sB7 cells were very sensitive to high-dose radiation-induced cell death, whereas Jurkat and JM1 cells showed moderate sensitivity, and THP-1 cells were completely resistant. This radiosensitivity was correlated with basal AKT activation, which is induced by phosphorylation. In radiosensitive IM-9 cells, priming with chronic low-dose irradiation blocked cell death induced by high-dose radiation challenge via inhibition of caspase activation and PARP cleavage. AKT phosphorylation was not altered in IM-9 cells, but ERK phosphorylation was greatly elevated immediately after chronic low-dose irradiation. Taken together, our results suggest that the different responses of normal and tumor cells to low-dose and high-dose radiation depend on AKT activation, which is regulated by protein phosphatase 2 (PP2A). In radiosensitive normal cells lacking basal AKT activity, chronic low-dose radiation increases activation of the ERK pathway, which plays an important role in the adaptive response to radiation, providing a very important insight into understanding the effects of ionizing radiation on health.


Facial Rejuvenation with Fast Recovery Suspension Technique.
Minimally invasive facial rejuvenation techniques are gaining attention because of their advantages such as less trauma, quick recovery, high safety, obvious results, and repeatable operation. In this article, the principle, the operation method, advantages, and disadvantages of the new fast recovery suspension technique modified by the authors are described in detail, and the clinical cases are listed to further illustrate the efficacy of the modified operation. The authors also compared this procedure with other common facial rejuvenation techniques. It is hoped that our article can provide a reference for clinicians to better use facial rejuvenation technology.


Pegylated liposomal doxorubicin in combination with gemcitabine: a phase II study in anthracycline-naïve and anthracycline pretreated metastatic breast cancer patients.
The aim of the study was to assess the toxicity profile, activity in terms of response rate, time to progression, overall survival, and quality of life of pegylated liposomal doxorubicin (PLD) and gemcitabine combination in chemo-naïve and pretreated metastatic breast cancer (MBC) women. Patients were eligible if they had disease progression to prior chemotherapy (anthracycline-including or not) for early breast cancer or MBC. Patients received PLD 25 mg/m(2) intravenously on day 1 plus gemcitabine 800 mg/m(2) intravenously on days 1 and 8 of each 21-day cycle. Of 50 patients enrolled, 37 had received prior adjuvant chemotherapy (24 with an anthracycline) and 23 prior chemotherapy for metastatic disease (6 with an anthracycline). Two complete responses and 20 partial responses were achieved in 46 assessable patients (overall response rate: 47.8%). Responses were observed in 14 (46.6%) of 30 patients with previous anthracycline exposure. Median response duration was 7 months, median duration of clinical benefit 8 months, time to progression 7 months. At a median follow-up of 10 months, 79.4% patients were alive at 1 year. No neutropenic complication was observed. Non-hematological toxicities were mild. One patient previously treated with an anthracycline developed a transient decrease (26%) in the left ventricular ejection fraction, with cardiac function recovering within 6 months. Because of the non-overlapping toxicity profiles of both PLD and gemcitabine, this combination can be regarded as a reliable therapeutic option for patients who have failed previous treatments, including anthracycline, for MBC.


Antibiotic resistance of Gardnerella vaginalis in recurrent bacterial vaginosis.
Fifty strains of Gardnerella vaginalis isolated from 321 high vaginal swabs over a period of five months were tested for their antibiotic sensitivity. Sixty eight per cent of all isolates were resistant to metronidazole while 76% were sensitive to clindamycin. All the strains isolated from cases with recurrence of infection were resistant to metronidazole. Clindamycin therapy has a better clinical efficacy than metronidazole in cases of recurrent bacterial vaginosis.


Single-cannula venovenous bypass for respiratory membrane lung support.
Clinical use of a single cannula would make extracorporeal membrane oxygenation simpler and less aggressive. It would probably limit the occurrence of the complications of currently used techniques (double-cannula, venoarterial, or venovenous bypass). In this experimental study an original system is described that is composed of a single cannula, an alternating clamp, and a nonocclusive roller pump, the characteristics of which permit its use as a venous reservoir. To overcome the limitations of the oxygenation in any venovenous bypass, we used the method of "apneic oxygenation" through the natural lungs, which we previously proved efficient in infants and children. The optimal setting of the alternative clamp was first tested in vitro to obtain the maximal flow in the circuit and the minimal amount of recirculation. The single-cannula bypass then was compared with a two-cannula circuit regarding the efficiency of carbon dioxide removal and the hemodynamic consequences. At less than 50% of the maximal speed of the pump, flows were equivalent in both types of circuits. The efficiency of carbon dioxide removal was only slightly decreased by the use of a single cannula (30 +/- 2 ml/min versus 36 +/- 2 ml/min with two cannulas). This could easily be offset by increasing the gas flow/blood flow ratio in the oxygenator. Arterial carbon dioxide tension was maintained at normal levels in both types of circuits. Hemodynamic condition was only slightly affected by the alternative flow of the bypass. This system of single-cannula membrane lung support thus seems to be adequate for clinical use.


Allergen-containing immune complexes used for immunotherapy of allergic asthma. Preparation of complexes and evaluation of their clinical performance in guinea pigs.
Guinea pigs inbred for their ability to develop respiratory anaphylaxis to experimental antigens have been used for comparison of different forms of immunotherapy (IT). Passive, active and combined (immune complexes between antigen and specific IgG) IT were compared with placebo. The bronchial reactivity of the animals to the antigen was monitored regularly before, during (35 weeks) and after IT (20 weeks). Animals treated with passive IT did not improve clinically. Active and combined IT abolished most symptoms within 7 weeks of treatment. During the post-treatment period, animals from both groups surprisingly recovered their original sensitivity to inhalation of the antigen.


Preparation and biomedical applications of programmable and multifunctional DNA nanoflowers.
We describe a comprehensive protocol for the preparation of multifunctional DNA nanostructures termed nanoflowers (NFs), which are self-assembled from long DNA building blocks generated via rolling-circle replication (RCR) of a designed template. NF assembly is driven by liquid crystallization and dense packaging of building blocks, which eliminates the need for conventional Watson-Crick base pairing. As a result of dense DNA packaging, NFs are resistant to nuclease degradation, denaturation or dissociation at extremely low concentrations. By manually changing the template sequence, many different functional moieties including aptamers, bioimaging agents and drug-loading sites could be easily integrated into NF particles, making NFs ideal candidates for a variety of applications in biomedicine. In this protocol, the preparation of multifunctional DNA NFs with highly tunable sizes is described for applications in cell targeting, intracellular imaging and drug delivery. Preparation and characterization of functional DNA NFs takes ∼5 d; the following biomedical applications take ∼10 d.


Resveratrol attenuates hydrogen peroxide-induced apoptosis in human umbilical vein endothelial cells.
Vascular endothelium injury caused by reactive oxygen species (ROS) plays an initial role in the pathogenesis of atherosclerosis. Resveratrol, a natural polyphenolic compound, is well known to possess a variety of cardioprotective activities. In this study we first investigated the effects of resveratrol against apoptosis of human umbilical vein endothelial cells (HUVECs) induced by hydrogen peroxide (H2O2) in vitro and the possible mechanisms. HUVECs were pre-incubated with resveratrol (0.5-10 microM) for 120 min, and then challenged with 100 microM H2O2 for 30 min. The cell viability was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The superoxide dismutase (SOD) activities and the reduced glutathione (GSH) contents were measured spectrophotometrically by using commercially available kits. The apoptosis of HUVECs was detected by Hoechst 33258 and Annexin-V/PI staining by flow cytometry staining using Fluorescence microscope. We also measured the mitochondrial membrane potential with the fluorescent probe JC-1 through Fluorescence microscope. The study showed that incubation with resveratrol caused significant increase of the viability of HUVECs and the SOD activities and GSH contents, and decrease of cell apoptosis induced by H2O2, which was accompanied with the restoration of the mitochondrial membrane potential. Our data suggested that resveratrol protected HUVECs against apoptosis induced by H2O2 through enhancing the antioxidant defenses, and inhibiting the degression of the mitochondrial membrane potential.


Ecological risk assessment based on soil adsorption capacity for heavy metals in Taihu basin, China.
Due to the toxicity, bioaccumulation, non-biodegradability and perseverance of heavy metals, their risk assessment is essential for soil quality management. The Hakanson potential ecological risk index (RI), which considers the effects of heavy metal concentration and toxicity, has been widely used in soil ecological risk assessment. However, RI overlooks the influence of soil properties on the mobility and availability of heavy metals in risk assessment. To fill this gap, this study sought to develop an improved ecological risk index (IRI), which incorporates soil adsorption into RI, and applied it to evaluate the ecological risk of heavy metals in the soil of the Taihu basin, China. The soil adsorption models based on the Gradient Boosting Decision Tree (GBDT) was used to predict the soil adsorption capacity of five heavy metals (i.e. cadmium, chromium, copper, lead, zinc). The soil adsorption capacity in 1446 sites in the Taihu basin was predicted by the GBDT models and was assigned as the weight of IRI. The risk assessment results of the five metals in the Taihu basin showed that 40% of the sites were at a moderate risk level and 60% of the sites were at a slight risk level based on the RI. The value of IRI in the basin ranged from 11.1 to 75.5, with a mean value of 28.1. IRI differed from RI in spatial distribution due to the influence of soil adsorption. The comparative analysis between the metal contents in sediments and surrounding soils confirmed the tremendous influence of soil adsorption on ecological risks, indicating that soil adsorption should be taken into consideration in soil risk assessment.


Monoclonal antibodies reactive with all strains of Haemophilus ducreyi.
We have isolated plasma cell hybridomas which secrete monoclonal antibodies directed against Haemophilus ducreyi. Two of these monoclonal antibodies recognize all strains of H. ducreyi tested to date and are capable of detecting the presence of H. ducreyi in skin lesions produced by this pathogen in experimental animals. These monoclonal antibodies which react with apparently all strains of H. ducreyi have the potential to be developed into a rapid immunodiagnostic test for chancroid.


A review of psychosocial factors linked to adolescent substance use.
Informed by ecological theories and models of influence, this review discusses various psychosocial risk and protective factors that contribute to adolescent substance use behavior. Given typical patterns of substance use initiation during this developmental period, an emphasis is placed on alcohol, cigarette, and marijuana use. Consistent with bioecological theories, peers and parents tend to have the strongest effect on adolescent substance use behavior. Influences can be both direct, such as offers and availability to use substances, as well as indirect influences, such as the perception of substance use approval. Schools and neighborhoods also contribute to adolescent substance use behavior, but this effect is often less direct. Moreover, the effect of neighborhoods on adolescent behavior reflects both structural components (e.g., neighborhood racial composition, teacher-student ratios) in addition to social process (e.g., neighborhood social cohesion, school connectedness). A review of parallel studies conducted with animals is also provided. Adolescent substance use behavior does not occur in a vacuum. Investigations must encompass the relevant social ecologies that affect adolescent behavior, including family, peer, school, and neighborhood contexts to provide a more complete understanding of substance use etiology.


High IL-17-positive tumor immune cell infiltration is indicative for chemosensitivity of ovarian carcinoma.
Ovarian carcinoma in most instances is diagnosed in an advanced stage which cannot be cured by surgical tumor debulking alone. Standard adjuvant chemotherapy usually follows surgical procedures. Yet, few reliable predictive tissue markers exist for the response of ovarian carcinoma to chemotherapy. In this study, we evaluated the predictive value of IL-17- and FOXP3-positive tumor immune cell infiltration (TICI) for response to chemotherapy in ovarian carcinoma. Formalin fixed and paraffin embedded biopsies of mostly high-grade primary serous ovarian carcinomas and their matched recurrences were immunostained with IL-17 and FOXP3 on a tissue microarray. Chemoresistance was defined as tumor recurrence within 6 months of the completion of platinum-based chemotherapy. In 94 and 90 biopsies, conclusive data for IL-17 and FOXP3 were available, respectively. IL-17, but not FOXP3-positive TICI, displayed a significantly higher density in biopsies of chemosensitive tumors (p = 0.01). No significant difference in the expression of IL-17 and FOXP3 TICI was observed in all paired primary and recurrent biopsies without respect to chemoresponse (p = 0.77 and p = 0.87, respectively). However, significantly more IL-17-positive recurrences were encountered in the group of patients with chemosensitive tumors (p = 0.008). High IL-17-positive TICI is indicative for response to chemotherapy in ovarian carcinoma. Higher frequency of IL-17-positive TICI might persist in recurrent tumor tissues of chemosensitive biopsies, suggesting repetitive platinum-based chemotherapy as an appropriate therapy for patients with IL-17-positive recurrences.


Multiple intramedullary nailing of pertrochanteric fractures with elastic nails: operative procedure and results.
Two hundred and sixty-six pertrochanteric fractures were operated on using intramedullary fixation according to the method of Ender and Simon-Weidner. Evaluation of both early and late results prove it to be a method with a low complication rate and a high incidence of functional recovery.


Efficacy and tolerability of anti-asthma herbal medicine intervention in adult patients with moderate-severe allergic asthma.
Chinese herbal medicine has a long history of human use. A novel herbal formula, anti-asthma herbal medicine intervention (ASHMI), has been shown to be an effective therapy in a murine model of allergic asthma. This study was undertaken to compare the efficacy, safety, and immunomodulatory effects of ASHMI treatment in patients with moderate-severe, persistent asthma with prednisone therapy. In a double-blind trial, 91 subjects underwent randomization. Forty-five subjects received oral ASHMI capsules and prednisone placebo tablets (ASHMI group) and 46 subjects received oral prednisone tablets and ASHMI placebo capsules (prednisone group) for 4 weeks. Spirometry measurements; symptom scores; side effects; and serum cortisol, cytokine, and IgE levels were evaluated before and after treatment. Posttreatment lung function was significantly improved in both groups as shown by increased FEV(1) and peak expiratory flow findings (P<.001). The improvement was slightly but significantly greater in the prednisone group (P<.05). Clinical symptom scores, use of beta(2)-bronchodilators, and serum IgE levels were reduced significantly, and to a similar degree in both groups (P<.001). T(H)2 cytokine levels were significantly reduced in both treated groups (P<.001) and were lower in the prednisone-treated group (P<.05). Serum IFN-gamma and cortisol levels were significantly decreased in the prednisone group (P<.001) but significantly increased in the ASHMI group (P<.001). No severe side effects were observed in either group. Anti-asthma herbal medicine intervention appears to be a safe and effective alternative medicine for treating asthma. In contrast with prednisone, ASHMI had no adverse effect on adrenal function and had a beneficial effect on T(H)1 and T(H)2 balance.


High pressure treatment under subfreezing temperature results in drastic inactivation of enveloped and non-enveloped viruses.
Some viruses are sensitive to high pressure. The freeze-pressure generation method (FPGM) applies pressure as high as 250 MPa on a substance, simply by freezing a pressure-resistant reservoir in which the substance is immersed in water. Here we examined whether the FPGM successfully inactivates herpes simplex virus type 1 (HSV-1), an enveloped DNA virus belonging to the human Herpesviridae, and encephalomyocarditis virus (EMCV), an envelope-free RNA virus belonging to the Picornaviridae. After the treatment, HSV-1 drastically reduced the ability to form plaque in Vero cells in vitro as well as to kill mice in vivo. EMCV that had been pressurized failed to proliferate in HeLa cells and induce interferon response. The results suggest that the FPGM provides a feasible procedure to inactivate a broad spectrum of viruses.


Taxonomy of Cyrtomorphus Lacordaire (Coleoptera, Erotylidae, Tritomini) from China.
In this paper, a key to separate the Chinese species of genus Cyrtomorphus Lacordaire is provided for the first time. A new species, Cyrtomorphus rufobrunneus sp. nov., is described and illustrated, and one species, Cyrtomorphus connexus Gorham, 1896 is newly recorded to China.


The Arterial Pattern of the Upper Nasal Septum (S-Point) and Potential Role in Severe Epistaxis.
The previously described S-point, corresponds to the medial projection of the middle turbinate axilla in the superior nasal septum and has been identified as a common source of severe epistaxis. The objective is to define the anatomical patterns of vascularization of the S-point area that could explain its clinical relevance. Thirty-three nasal septums of latex-injected formalin-embalmed and fresh human cadaveric heads were dissected to analyze the arterial arrangement of the S-point area. Measurements and patterns of vascularization were described. The S-point area, was consistently surrounded by a single or multiple arterial anastomotic arches consistently formed superiorly by the anterior ethmoidal and posterior ethmoidal artery branches, and inferiorly by the posterior septal artery. The caliber of the arterial arches was typically larger than the caliber of the arterial branches supplying them. A single arch was present in 36.3% of septums, and multiple arches in 63.6%. The mean distance from the S-point to the anterior limit of the arch was 9 mm, to the posterior arch when the present was 3 mm, to the superior limit 6 mm, to the inferior limit 6 mm, and to the nasal roof was 10 mm. This study demonstrates the dense arterial configuration of the S point area, which is characterized by a single or multiple vascular arches of greater caliber than the branches of origin. This finding could explain why the S-point area is a frequent source of epistaxis, and guide its surgical cauterization when an obvious vascular ectasia is not visualized. N/A Laryngoscope, 133:2075-2080, 2023.


Sources of anthropogenic lead in sediments from an artificial lake in Brasília-central Brazil.
Pb concentration and Pb isotopic composition are known to represent powerful tools to investigate the history of Pb pollution in water and sediments. In this paper, we present and discuss the results of a detailed study of sediments deposited in the Paranoá Lake, a 44-year-old artificial reservoir in Brasília, central Brazil. Pb concentration and isotopic composition of the sediments were obtained by ID-TIMS, on three different sample fractions: leachate, residue, and bulk sample. The leachate phase has proven to be most efficient to distinguish between anthropogenic and natural Pb inputs. In the Paranoá lake, important sources of contamination were recognized, producing higher Pb concentrations (max. 37.68 ppm) and significant variations in Pb isotopic composition, relative to the regional geogenic background. Contamination of the sediments due to anthropogenic activity produced less radiogenic Pb isotopic compositions (206Pb/207Pb=1.15-1.17), compared with the regional natural composition (206Pb/207Pb=1.19-1.25). 210Pb analyses along one bore hole which sampled the entire sediment section indicated a sedimentation rate of 8.2+/-1.8 mm/year. The combined use of the 210Pb ages and Pb isotopic compositions of these samples revealed three distinct periods in the lake history: (1) the period of the time formation of the lake in 1959 until ca. 1970 was characterized by the deposition of sediments displaying more radiogenic Pb isotopic signature, (2) the time interval from the start of the process of eutrophication at 1970, until 1995, was characterized by the deposition of sediments having less radiogenic average compositions, and (3) from 1995 until the present represents a period of recovery of water quality, after two sewage treatment stations started to operate.


Lower Limb Muscle Flaps: The Reverse Peroneus Brevis Flap.
Chronic ulcerations of the lower extremity centered around the lateral malleolus, medial malleolus, Achilles tendon, or anterior ankle are complex and difficult to heal with conventional treatment modalities. With the evolution of orthoplastics and microsurgery techniques, the peroneus brevis muscle flap has been shown to be simple, versatile, and effective in management of small to medium-sized soft tissue defects that may or may not have exposed bone, tendon, or both. This article reviews the peroneus brevis muscle flap in lower extremity reconstruction and presents pertinent real-world cases of its applications as a tool for limb salvage and orthoplastic reconstruction.


Carbon stocks of particle board and fiberboard in Japan.
The carbon stock function of harvested wood products (HWPs) is attracting attention among climate change countermeasures. Among HWPs, particle board (PB) and fiberboard (FB) mainly use recycled materials. This study estimated carbon stocks of PB and FB and their annual changes over the past 70 years in Japan using three methods of the Intergovernmental Panel on Climate Change guidelines: Tiers 1-3. Tier 1 uses first order decay (FOD), a 25-year half-life, and the Food and Agriculture Organization of the United Nations database. Tier 2 uses FOD, a 25-year half-life, and Japan-specific statistics. Tier 3 uses a log-normal distribution for the decay function and a 38-63-year half-life of building PB/FB. Japan's PB and FB carbon stocks have increased for the past 70 years. The latest carbon stock in early 2022 and the annual change in carbon stock in 2021 was 21.83 million t-C and 0.42 million t-C/year, respectively for Tier 3. Tier 3 has the highest estimation accuracy by using decay functions and half-lives that match the actual conditions of building PB and FB, whereas Tiers 1 and 2 were underestimates. Approximately 40% of the carbon stock is derived from waste wood, which extends its utilization.


Patterns of senescence and apoptosis during development of branchial arches, epibranchial placodes, and pharyngeal pouches.
Many developmental processes are coregulated by apoptosis and senescence. However, there is a lack of data on the development of branchial arches, epibranchial placodes, and pharyngeal pouches, which harbor epibranchial signaling centers. Using immunohistochemical, histochemical, and 3D reconstruction methods, we show that in mice, senescence and apoptosis together may contribute to the invagination of the branchial clefts and the deepening of the cervical sinus floor, in antagonism to the proliferation acting in the evaginating branchial arches. The concomitant apoptotic elimination of lateral line rudiments occurs in the absence of senescence. In the epibranchial placodes, senescence and apoptosis appear to (1) support invagination or at least indentation by immobilizing the margins of the centrally proliferating pit, (2) coregulate the number and fate of Pax8+ precursors, (3) progressively narrow neuroblast delamination sites, and (4) contribute to placode regression. Putative epibranchial signaling centers in the pharyngeal pouches are likely deactivated by rostral senescence and caudal apoptosis. Our results reveal a plethora of novel patterns of apoptosis and senescence, some overlapping, some complementary, whose functional contributions to the development of the branchial region, including the epibranchial placodes and their signaling centers, can now be tested experimentally.


Structural and functional neuroimaging in patients with Parkinson's disease and visual hallucinations: A critical review.
Patients with Parkinson's disease (PD) may develop various non-motor symptoms (NMS) during the course of the illness and psychosis is one of the common NMS of PD. Visual hallucinations (VH) are the most common manifestation of psychosis in PD. The exact pathogenesis of VH in patients with PD is not clearly understood. Presence of VH has been described to be associated with rapid cognitive decline and increased nursing home placements in PD patients. A large number of structural and functional neuroimaging studies have been conducted to understand the cerebral basis of VH in PD. Structural imaging studies (Voxel Based Morphometry) have reported grey matter atrophy in multiple regions of the brain such as primary visual cortex, visual association cortex, limbic regions, cholinergic structures such as pedunculopontine nucleus and substantia innominata, which conclude possible alterations of brain regions associated with functions such as visuospatial-perception, attention control and memory. Most functional neuroimaging studies (functional MRI, positron emission tomography and single photon emission computerized tomography) have reported altered activation, blood flow, or reduced metabolism in both dorsal and ventral visual pathways, which probably indicates an alteration in the normal bottom-top visual processing and the presence of an aberrant top-down visual processing. This review critically analyzes the published studies on the structural and functional neuroimaging in PD patients with VH.


Ceruloplasmin levels in the human superior temporal gyrus in aging and Alzheimer's disease.
In the present study we observed a loss in excess of 1/3 of the copper transport and anti-oxidant protein ceruloplasmin in both the gray and white matter from superior temporal gyrus in Alzheimer's diseased brains compared to age-matched controls. A decrease in ceruloplasmin could be reflected in decreased cellular metabolic processes such as the electron transport system and a decrease in the ability of the brain to protect itself from oxidative damage. Both decreased metabolic activity and an increase in oxidative insults are known to be associated with the neurological events in Alzheimer's disease, but the mechanism by which these phenomena occur are unknown. These results coupled with previous reports from this laboratory on iron regulatory proteins in the brain suggests one way in which cellular dysfunction and oxidative stress occurs in AD may be through a loss of ability to maintain a balance of essential metals.


Bio-integrative design of the neural tissue-device interface.
Neural implants enable bidirectional communications with nervous tissue and have demonstrated tremendous potential in research and clinical applications. To obtain high fidelity and stable information exchange, we need to minimize the undesired host responses and achieve intimate neuron-device interaction. This paper highlights the key bio-integrative strategies aimed at seamless integration through intelligent device designs to minimize the immune responses, as well as incorporate bioactive elements to actively modulate cellular reactions. These approaches span from surface modification and bioactive agent delivery, to biomorphic and biohybrid designs. Many of these strategies have shown effectiveness in functional outcome measures, others are exploratory but with fascinating potentials. The combination of bio-integrative strategies may synergistically promote the next generation of neural interfaces.


The effect of growth hormone-induced cellular behavior and signaling properties on induced cellular senescence in human mesenchymal stem cells.
Senescence is associated with a decline in physiological function, which is accompanied by onset of diseases. Growth hormone (GH) is a class of growth-promoting cytokines with reduced secretion in aging populations. However, the effect of senescence on GH bioactivity is not fully understood in human mesenchymal stem cells (hMSCs). In this work, GH-induced cellular behavior and intracellular signaling transduction were explored in senescent hMSCs. Therefore, hMSCs were used to establish a senescence model by H2O2 treatment for this study. First, we investigated the effects of cellular senescence on the cell behavior of GH. The experimental results suggested that GH could not be internalized into the nucleus, and a significant reduction in GH internalization into the cytoplasm was observed in senescent hMSCs compared to the control group. Second, the effect of cellular senescence on GH-mediated intracellular signaling pathways was investigated by Western blotting. For this, the signaling molecule activation of Janus kinase 2 (JAK2)/signal transducer and activator transcription (STAT) stimulated by GH was detected. Our data indicated that the signaling intensity of p-JAK2, p-STAT5, p-STAT3 and p-STAT1 was considerably weakened. Taken together, these findings provide important insights into the impaired effects of cellular senescence on the biological activity of GH.


Reductive metabolism of tiaprofenic acid by the human liver and recombinant carbonyl reducing enzymes.
Tiaprofenic acid is a widely used anti-inflammatory drug; however, the reductive metabolism of tiaprofenic acid is not yet well understood. Here, we compared the reduction of tiaprofenic acid in microsomes and cytosol from the human liver. The microsomes exhibited lower Km value toward tiaprofenic acid than the cytosol (Km = 164 ± 18 μM vs. 569 ± 74 μM, respectively), whereas the cytosol showed higher specific activity during reduction than the microsomes (Vmax = 728 ± 52 pmol mg of protein-1 min-1 vs. 285 ± 11 pmol mg of protein-1 min-1, respectively). Next, a panel of recombinant carbonyl reducing enzymes from AKR and SDR superfamilies has been studied to find the enzymes responsible for the cytosolic reduction of tiaprofenic acid. CBR1 was identified as the reductase of tiaprofenic acid with high specific activity (56,965 ± 6741 pmol mg of protein-1 min-1). Three other enzymes, AKR1A1, AKR1B10, and AKR1C4, were also able to reduce tiaprofenic acid, but with very low activity. Thus, CBR1 was shown to be a tiaprofenic acid reductase in vitro and was also suggested to be the principal tiaprofenic acid reductase in vivo.


Body mass index and adverse events in patients with incident atrial fibrillation.
Obesity is associated with the development of atrial fibrillation and may impact atrial fibrillation-related outcomes. To date, no anthropometric measure is included in any risk stratification scheme for stroke and death in atrial fibrillation patients. The prospective Danish Diet, Cancer and Health study is a cohort including 57,053 participants (27,178 men and 29,875 women) aged between 50 and 64 years. The study population for this study included the 3135 patients (2025 men and 1110 women) who developed incident atrial fibrillation during follow-up. Of the subjects with atrial fibrillation, 1414 (45%) had a body mass index (BMI) in the overweight category (BMI 25 to <30 kg/m(2)) and 767 (24%) were categorized as obese (BMI ≥30 kg/m(2)). During a median follow-up of 4.9 years, 609 deaths and 216 thromboembolic events (98% ischemic strokes) occurred. Using normal-weight patients as reference, the risk of a composite end point of "ischemic stroke, thromboembolism, or death" was significantly higher in overweight (crude hazard ratio [HR] 1.31; 95% confidence interval [CI], 1.09-1.56) and obese patients (crude HR 1.55; 95% CI 1.27-1.90). After adjustment for CHADS2 and CHA2DS2-VASc scores, the HRs for the composite end point were 1.21 (95% CI 1.02-1.45) and 1.31 (95% CI 1.10-1.56), respectively, for overweight and 1.25 (95% CI 1.03-1.53) and 1.36 (95% CI 1.11-1.65), respectively, for obese. Continuous analyses of BMI stratified by sex identified obese men and normal-weight women as the sex-specific "high-risk" categories. Overweight and obesity are risk factors for "ischemic stroke, thromboembolism or death" in patients with atrial fibrillation, even after adjustment for CHADS2 and CHA2DS2-VASc scores. The association between BMI and outcomes among atrial fibrillation patients may be modified by sex.


Human cord blood--derived cells generate insulin-producing cells in vivo.
Here we report the capacity of human cord blood (CB)-derived cells to generate insulin-producing cells. To investigate in vivo capacity of human CB-derived cells, T cell-depleted mononuclear cells were intravenously transplanted into nonobese diabetic/severe combined immunodeficient/beta2-microglobulinnull mice within 48 hours of birth. At 1-2 months post-transplantation, immunofluorescence staining for insulin and fluorescence in situ hybridization (FISH) analysis using a human chromosome probe indicated that human CB-derived cells generated insulin-producing cells at a frequency of 0.65%+/-0.64% in xenogeneic hosts. Reverse transcription-polymerase chain reaction analysis confirmed the transcription of human insulin in the pancreatic tissue of the recipient mice. To clarify the mechanism underlying CB-derived insulin-producing cells, double FISH analysis using species-specific probes was performed. Almost equal proportions of human chromosome+ murine chromosome- insulin+ cells and human chromosome+ murine chromosome+ insulin+ cells were present in recipient pancreatic islets. Taken together, human CB contains progenitor cells, which can generate insulin-producing cells in recipient pancreatic tissues across a xenogeneic histocompatibility barrier by fusion-dependent and -independent mechanisms.


Three-dimensional identification of actin filaments in phalloidin-treated rat livers by quick-freezing and deep-etching method.
An increase in microfilaments in phalloidin-treated hepatocytes of Wistar rats was identified three-dimensionally with myosin subfragment 1 (S1) on replica membranes, using the quick-freezing and deep-etching method. Almost all of the reticular microfilaments around the bile canaliculi and beneath the lateral cell membranes were decorated on their surfaces by S1 attachment. Some showed periodic structures. However, thinner filaments with diameters of 4-7 nm were not decorated by S1. Bundled intermediate filaments around the bile canalicular microfilaments and intermediate filaments localized among cell organelles had smooth surfaces without S1 decoration. The microfilaments decorated by S1 were attached directly to bundled intermediate filaments. The quick-freezing and deep-etching method is useful in analysing cytoskeletal pathology and can be applied to histochemical fields.


Binding studies of creatinine and urea on iron-nanoparticle.
Kidney diseases are complicated and can be fatal. Dialysis and transplantation are the only survival solutions to the patients suffering from kidney failures. Both hemodialysis and peritoneal dialysis are risky, due to the possibility of infection and these are expensive and time consuming. The development of simple and reliable technique for the clearance of creatinine and urea from the body is an important part of biotechnology. We have synthesized an iron nanoparticle (INP) and studied its binding with creatinine and urea. The DLS, TEM, AFM, FT-IR and Powder-XRD studies demonstrate strong binding of creatinine and urea to the nanoparticles. This finding may be helpful if it is used in the dialysis technologies. The proposed method may substantially decrease dialysis time and improve its quality in terms of urea and creatinine clearances.


Arthritis associated with venereal disease in nineteenth century London.
It is well known that arthritis can be associated with venereal disease. Nowadays septic arthritis and reactive arthritis (usually classified as Reiter's syndrome) are distinguished. To place current knowledge within its historical context we reviewed the medical literature on sexually acquired arthritis in the nineteenth century and examined the medical records of London teaching hospitals from this period. We used original sources of rheumatological literature at major London libraries, including the Heberden library of the Royal College of Physicians, and visited the archives at three London teaching hospitals to review original case records and examine diagnostic registers. The first clear description of arthritis associated with venereal disease was given by Swediaur (1798/1809) in French. It became relatively common in London from 1820 onwards with 13 cases described in the literature between 1818 and 1836. It accounts for 3% of admissions at University College and St Bartholomew's Hospitals between 1835 and 1839 and also 3% of admissions at the London Hospital from 1895 to 1900. In the 50 years after Swediaur's report, arthritis associated with venereal disease seemed quite common. This may have been related to the industrial revolution or other social diseases. Historical observations suggest its evidence may vary considerably with time.


Neck subcutaneous nodule as first metastasis from broad ligament leiomyosarcoma: a case report and review of literature.
Leiomyosarcoma usually develops in the myometrium and is characterized by a high recurrence rate, frequent hematogenous dissemination, and poor prognosis. Metastasis is usually to lungs, liver, and bone, and occasionally to the brain, but seldom to the head and neck region. Primary leiomyosarcoma very rarely arises in the broad ligament. A 54-year old woman presented to the otolaryngology department with a mass in the right posterior region of the neck 4 years after surgery for a primary leiomyosarcoma of the right broad ligament. The neck mass was removed and found to be a metastatic leiomyosarcoma. Leiomyosarcoma localizations in lungs and liver were absent. Morphological examination showed both the primary and the secondary leiomyosarcomas to have features of low-grade tumors. One year after excision of the neck mass, the patient presented with tachycardia. Echocardiography detected two intracardiac nodules suggestive of metastatic tumors. Chemotherapy was administered; the disease has been stable since then. We report the first case of broad ligament leiomyosarcoma with the neck subcutaneous region being the first site of secondary involvement. We speculate that the Batson venous plexus might have been the pathway of dissemination.


Characterization of the novel HLA-DRB1*13:320 allele by next-generation sequencing.
HLA-DRB1*13:320 differs from HLA-DRB1*13:02:01:02 by one nucleotide substitution in codon 22 in exon 2.


Treatment of multiple drug-resistant tuberculosis (MDR-TB) in Iran.
Masih Daneshvari Hospital, Tehran, Iran, 2000-2002. To evaluate the effectiveness of multiple drug-resistant tuberculosis (MDR-TB) treatment for the first time in Iran. All cases of MDR-TB with complete follow-up data were recruited and results of their treatments were evaluated. MDR-TB treatment was initiated with 5.23 drugs, on average. Isoniazid, amikacin, and ofloxacin were present in the drug regimen of all patients. Average duration of the treatment was 18.5 months (range, 7-36). Over 76% of the patients responded to the treatment (negative smear and culture). Cure and probable cure were documented in seven (41.2%) and four (23.5%) of the patients, respectively. No failure in the treatment occurred when cycloserine was present in the treatment regimen. A majority of the MDR-TB patients in Iran can be cured with the use of appropriate treatment regimens. An even greater success could be achieved by providing more second-line drugs.


Nanosizing by spatially modulated illumination (SMI) microscopy and applications to the nucleus.
In this chapter we present the method of spatially modulated illumination (SMI) microscopy, a (far-field) fluorescence microscopy technique featuring structured illumination obtained via a standing wave field laser excitation pattern. While this method does not provide higher optical resolution, it has been proven a highly valuable tool to access structural parameters of fluorescently labeled macromolecular structures in cells. SMI microscopy has been used to measure relative positions with a reproducibility of <2 nm between fluorescing objects. Among others, we have measured size distributions of protein clusters with an accuracy much better than the resolution achievable e.g. in confocal microscopy. The advantages of the SMI microscope over other (ultra-)high resolution light microscopes are its easy sample preparation and microscope handling as well as the comparably fast acquisition times and large fields of view.


Utility of EBUS-TBNA in diagnosing mediastinal tuberculous lymphadenitis in East London.
To characterise and describe the diagnostic utility of Endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) in intrathoracic tuberculosis in a cohort of patients with mediastinal lymphadenopathy of unknown aetiology. Consecutive patients with intrathoracic lymphadenopathy undergoing EBUS-TBNA between 2012 and 2016 were identified. Demographic data, biopsy cytopathology and mycobacteriology results, HIV and vitamin D status, susceptibility results and final diagnoses were recorded. Pre- and post-procedure probability scores were assigned to each case to reflect the probability of tuberculosis. 315 cases were identified; 54 (17.1%) had tuberculosis and 261 (82.9%) had a non-tuberculosis diagnosis. amongst TB cases, the sensitivity of EBUS-TBNA was 59.3% (95% CI 45.06-72.14), specificity 100% (95% CI 98.19-100) and the negative predictive value (NPV) was 92.23% (95% CI 88.31-94.95). 19/54 (35%) TB cases were confirmed by EBUS mycobacterial culture and 13/54 (24.1%) by cytopathology. 33 (61.1%) of the TB cases, had a low to medium pre-test probability score assigned prior to EBUS-TBNA. Amongst EBUS culture-confirmed cases, we found a resistance rate of 10.5% to one or more first line TB drugs, with one case of multi-drug resistant TB. We confirmed the utility of EBUS-TBNA in the diagnosis of intrathoracic tuberculosis in an undifferentiated cohort of patients with mediastinal lymphadenopathy of unknown aetiology and advocate sending samples for mycobacterial culture in all cases in high tuberculosis incidence areas.


Corporal punishment of children in Australia: The evidence-based case for legislative reform.
Across all of Australia's states and territories, it is legal for a parent or carer to hit their child. In this paper, we outline the legal context for corporal punishment in Australia and the argument for its reform. We review the laws that allow corporal punishment, the international agreements on children's rights, the evidence on the effects of corporal punishment, and outcomes of legislative reform in countries that have changed their laws to prohibit corporal punishment. Legislative reform typically precedes attitude changes and reductions in the use of corporal punishment. Countries with the most ideal outcomes have instigated public health campaigns educating the population about law reform while also providing access to alternative non-violent discipline strategies. Extensive evidence exists demonstrating the adverse effects of corporal punishment. When countries change legislation, educate the public about these effects, and provide alternative strategies for parents, rates of corporal punishment decrease. We recommend law reform in Australia to prohibit corporal punishment, a public health campaign to increase awareness of corporal punishment and its effects, provision of access for parents to alternative evidence-based strategies to assist in parenting, and a national parenting survey to monitor outcomes.


A radioimmunoassay for norethindrone (NET): measurement of serum NET concentrations following ingestion of NET-containing oral contraceptive steroids.
A sensitive and reliable radioimmunoassay (RIA) for the measurement of norethindrone (NET) in serum has been established employing anti-11 alpha-hydroxynorethindrone 11-hemisuccinyl-bovine serum albumin serum in conjunction with norethindrone-3-(0-carboxymethyl) oximino-[125I]-iodohistamine. Of a number of ring A reduced NET metabolites, only 17 beta-hydroxy-17 alpha-ethinyl-5 beta-estran-3-one (43%) and 17 alpha-ethinyl-5 alpha-estrane-3 beta, 17 beta-diol (15.7%) cross-reacted appreciably in this RIA. Ethinyl estradiol (EE2) and mestranol (MEE2) exhibited cross-reactions of only 1.1 and 0.4%, respectively. Serum NET levels were measured in four groups of 3 women, each ingesting either 1 mg NET plus 0.05 mg MEE2 (Norinyl 1 + 50 or Ortho Novum 1/50), 0.5 mg NET plus 0.035 mg EE2 (Brevicon) or only 0.35 mg NET (Micronor) daily for 5 consecutive days. Peak serum NET levels were observed within 1/2 to 4 hours after oral intake and fell precipitously thereafter. After reaching a maximum, serum NET concentrations declined in a manner consistent with at least two disposition phases. The average half-life for the first disposition phase was 2.3, 3.4, 3.9 and 4.4 hours in subjects ingesting Norinyl 1 + 50, Ortho Novum 1/50, Brevicon and Micronor, respectively. Peak and 3-hour post-ingestion serum NET concentrations were dose-related but showed considerable subject-to-subject variations. Following discontinuation of tablet intake, serum NET levels remained detectable (greater than 0.05 ng/ml) for at least 5 days in all 3 women who had taken Ortho Novum 1/50, but in none of the other 9 volunteers. These results suggest that different preparations of identical doses and combinations of oral contraceptive steroids may yield different serum NET profiles. However, due to considerable subject-to-subject variations, larger numbers of subjects are required for a conclusive investigation.


Digital fabrication of customized intraoral appliances for head and neck radiotherapy.
The radiotherapy received by head and neck cancer patients commonly has adverse effects on oral tissue and the muscles of mastication. This short communication describes the digital fabrication of intraoral appliances for radiotherapy and muscle exercises. Three patients diagnosed with tongue squamous carcinoma were treatment-planned for radiotherapy using different radiation techniques. The patients were referred for oral scanning and digital bite records, and the appliance was collaboratively designed by a radiation oncologist, dentist, and laboratory technician. The appliance covered the occlusal surface of the remaining teeth with a 1-mm engagement. The lingual plate was 2-mm below the occlusal plane, and extended 4-mm distally, and the jaws were opened by 20-mm. The appliances were printed overnight using a rigid and biocompatible 3D printing material. Requiring minimal chair-time, the appliance was easily inserted and adjusted to comfortably fit in the mouth. The patients were trained to insert it themselves. The tongue was at a pre-determined position during daily radiotherapy, and the healthy tissues were separated from the radiation field. The patients had mild adverse effects on their oral mucosa. Additionally, the appliances were used for muscle exercises after the radiation courses to prevent trismus. The interprofessional collaboration to fabricate customized intraoral appliances using digital workflow to maximize patients' benefits is feasible. The use of intraoral appliances is potentially increased when the fabrication process is facilitated. Using an intraoral appliance precisely targets the tumor are for better treatment outcomes, and the healthy adjacent tissues will be preserved to maintain the patient's quality of life.


MNE-BIDS: Organizing electrophysiological data into the BIDS format and facilitating their analysis.
The development of the Brain Imaging Data Structure (BIDS; Gorgolewski et al., 2016) gave the neuroscientific community a standard to organize and share data. BIDS prescribes file naming conventions and a folder structure to store data in a set of already existing file formats. Next to rules about organization of the data itself, BIDS provides standardized templates to store associated metadata in the form of Javascript Object Notation (JSON) and tab separated value (TSV) files. It thus facilitates data sharing, eases metadata querying, and enables automatic data analysis pipelines. BIDS is a rich system to curate, aggregate, and annotate neuroimaging databases.


Peripartum hysterectomy due to severe postpartum hemorrhage: A hospital-based study.
A peripartum hysterectomy is typically performed as a lifesaving procedure in obstetrics to manage severe postpartum hemorrhage. Severe hemorrhages that lead to peripartum hysterectomies are mainly caused by uterine atony and placenta accreta spectrum disorders. In this study, we aimed to estimate the incidence, risk factors, causes and management of severe postpartum hemorrhage resulting in peripartum hysterectomies, and to describe the complications of the hysterectomies. Eligible women had given birth at gestational week 23+0 or later and had a postpartum hemorrhage ≥1500 mL or a blood transfusion, due to postpartum hemorrhage, at Oslo University Hospital, Norway, between 2008 and 2017. Among the eligible women, this study included those who underwent a hysterectomy within the first 42 days after delivery. The Norwegian Medical Birth Registry provided the reference group. We used Poisson regression to estimate adjusted incidence rate ratios with 95% confidence intervals to identify clinical factors associated with peripartum hysterectomy. The incidence of hysterectomies with severe postpartum hemorrhage was 0.44/1000 deliveries (42/96313). Among the women with severe postpartum hemorrhage, 1.6% ended up with a hysterectomy (42/2621). Maternal age ≥40, previous cesarean section, multiple pregnancy and placenta previa were associated with a significantly higher risk of hysterectomy. Placenta accreta spectrum disorders were the most frequent cause of hemorrhage that resulted in a hysterectomy (52%, 22/42) and contributed to most of the complications following the hysterectomy (11/15 women with complications). The rate of peripartum hysterectomies at Oslo University Hospital was low, but was higher than previously reported from Norway. Risk factors included high maternal age, previous cesarean section, multiple pregnancy and placenta previa, well known risk factors for placenta accreta spectrum disorders and severe postpartum hemorrhage. Placenta accreta spectrum disorders were the largest contributor to hysterectomies and complications.


Legal provisions and practice in the management of violent patients. a case vignette study in 16 European countries.
To compare the clinical management of typical scenarios by using three case vignettes in a substantial number of European countries. Three case vignettes and an associated questionnaire, filled in and finalised by at least two experts from each country. Legislation and clinical practice varies widely across the 16 included countries. No specific pattern emerged. Certain practices (intravenous medication, mechanical restraint, net beds and forensic transfers, respectively) only exist in few countries. Legislation for involuntary medication is most restrictive in the Netherlands. There is little harmonisation and a lack of consistent standards within and across European countries regarding treatment and management of violent patients.


A step ahead to enhancing routine breast cancer resection: Spheroid and hen's egg chorioallantoic membrane models to assess the photodynamic diagnosis efficiency of ALA and PSI-ALA-hex.
Aminolevulinic acid (ALA) and its derivatives have been used in the diagnosis of several diseases through topical, intravesical, and oral administration. However, their intravenous use for the theranostics of cancers has not raised interest despite its potential advantages. In this study, we compared the efficacy of ALA, its hexyl ester ALA-Hex, and our new derivative PSI-ALA-Hex to induce a fluorescent protoporphyrin IX (PpIX) overproduction in breast cancers. First, we tested the drugs on four subtypes of breast cancer spheroids in vitro. Our results demonstrated the capacity of ALA-Hex and PSI-ALA-Hex to produce PpIX in all breast spheroids, although ALA struggled in half of the models. We applied the chick embryo in vivo model to investigate the intravenous administration route of ALA and PSI-ALA-Hex, ALA-Hex being toxic. We engrafted breast cancer nodules having various hormonal profiles onto the chorioallantoic membrane of the eggs. They were all detected by fluorescence imaging with mild efficacy using PSI-ALA-Hex, which displayed a maximum selectivity of 2.2 to 2.9, whereas ALA showed a higher selectivity from 3.2 to 5.1 at 300 μmol/kg. PSI-ALA-Hex was less appropriate for the diagnosis of breast cancer by intravenous administration. We show for the first time, to the best of our knowledge, the photodetection and imaging of a wide range of breast tumors in vivo upon intravenous treatment with ALA.


Transcriptional mechanisms in osteoblast differentiation and bone formation.
Osteoblasts, the cells responsible for bone formation, differentiate from mesenchymal cells. Here, we discuss transcription factors that are involved in regulating the multistep molecular pathway of osteoblast differentiation. Runx2 and Osx, a newly identified zinc-finger-containing protein, are transcription factors that are expressed selectively and at high levels in osteoblasts. Null mutations of either leads to a complete absence of bone in mice. Runx2 plus its companion subunit Cbf beta are needed for an early step in this pathway, whereas Osx is required for a subsequent step, namely the differentiation of preosteoblasts into fully functioning osteoblasts. The finding that Osx-null cells acquire a chondrocyte phenotype implies that Osx is a negative regulator of Sox9 and of the chondrocyte phenotype. This leads to the hypothesis that Osx might have a role in the segregation of osteoblasts from osteochondroprogenitors. We also discuss recent progress in studies of other transcription factors that affect skeletal patterning and development.


Immunoregulatory cells in aging mice. I. Concanavalin A-induced and naturally occurring suppressor cells.
The status of concanavalin A (Con A)-triggered suppressor cells in aging mice was assessed in relation to untreated cells. Spleen cells of (C3H/ebJ X C57BL/6J)F1 and (BALB/cJ X C57BL/6J)F1 aging (20-41 months' old) and young (2-3 months' old) mice were triggered with Con A and examined for their capacity to suppress lymphocyte proliferative responses elicited by mitogens (Con A and phytohemagglutinin), by mixed lymphocyte reactions or by human gamma-globulin. Con A-triggered cells of the aging mice were found to be less efficient suppressors than those of the young, yet the aging mouse spleen cells exerted a more potent suppressive effect than the young, a priori, without pretreatment. Hence, the immune system in aging is characterized by a change in suppressor cell types; the Con A-triggered suppressors diminish and the naturally occurring, untreated ones become abundant.


Deriving valid population-based cancer survival estimates in the presence of nonnegligible proportions of cancers notified by death certificates only.
Studies of cancer survival by population-based cancer registries are a key component in monitoring progress against cancer. Patients notified by death certificates only (DCO) are commonly excluded from such studies. The validity of this "exclude DCO" approach has been questioned and an alternative "correct for DCO" approach has been proposed. We assess the validity of both the "exclude DCO" approach and the "correct for DCO" approach using model calculations. We illustrate implications for population-based cancer survival analyses by analyses of 5-year relative survival of cancer patients in Saarland, Germany. The "exclude DCO" approach provides (too) optimistic survival estimates and the "correct for DCO" approach provides (too) pessimistic survival estimates under plausible assumptions. For example, in case of true survival of 50%, underascertainment of 5% of surviving patients and of 15% of dying patients (yielding a proportion of DCO cases of 7.7%), the two approaches would provide survival rate estimates of 52.8% and 48.8%, respectively. The difference of survival estimates obtained with both approaches increases with incompleteness of registration and the proportion of DCO cases. Trace back of DCO cases shifts survival estimates from the former toward the latter estimate. In case of nonnegligible DCO proportions, cancer survival studies should not be exclusively based on either the "exclude DCO" or the "correct for DCO" approach. A combination of estimates from both approaches may be useful to delineate a plausibility range for true survival. Our results may help to enhance validity and comparability of population-based cancer survival estimates.