Altered expression of oligopeptide-binding protein (OppA) and aminoglycoside resistance in laboratory and clinical Escherichia coli strains.
Oligopeptide-binding protein (OppA) is the periplasmic component of the major oligopeptide transport system of enteric bacteria. Genetic and biochemical evidence suggests that OppA plays a role in the uptake of aminoglycoside antibiotics in Escherichia coli K-12. Forty-six (82%) of 56 aminoglycoside-resistant mutants of E. coli K-12 selected in vitro had reduced or undetectable OppA levels, as compared with their parent strain. Moreover, nine (36%) of 25 aminoglycoside-resistant clinical isolates of E. coli expressed reduced or undetectable levels of OppA. No decrease in OppA expression was observed among aminoglycoside-sensitive E. coli strains from patients. Twenty-three (42%) of 56 aminoglycoside-resistant mutants of E. coli K-12 and six (24%) of 25 clinical isolates also were deficient for expression of ornithine or arginine decarboxylases, or both, and these deficiencies might negatively affect OppA expression by reducing polyamine synthesis. These results support the view that reduced OppA expression is associated with aminoglycoside resistance in E. coli strains.


Atrial-specific pathways for control of intracellular signaling and myocyte function.
Atrial fibrillation (AF) is a cardiac arrhythmia that arises from electrical and contractile dysfunction in the atria. Atrial function is regulated by a variety of intracellular signaling networks that facilitate rapid communication and coordinate responses of atrial myocytes. In this issue of the JCI, Brandenburg and colleagues describe the identification and characterization of "super-hub" signaling nodes located on atrial axial tubules that regulate atrial contraction. Together, the results of this study provide important insight into the regulation of atrial contraction and describe potential therapeutic targets to be explored in future studies.


Phase-conjugate holographic lithography based on micromirror array recording.
We present phase-conjugate holographic lithography with a hologram recorded by a digital micromirror device (DMD) and a telecentric lens. In our lithography system, a phase-conjugate hologram is applied instead of conventional masks or reticles to form patterns. This method has the advantage of increasing focus range, and it is applicable to the formation of patterns on fairly uneven surfaces. The hologram pattern is dynamically generated by the DMD, and its resolution is mainly determined by the demagnification of the telecentric lens. We experimentally demonstrate that our holographic lithographic system has a large focus range, and it is feasible to make a large-area hologram by stitching each pattern generated by the DMD without a falling off in resolution.


Can Insectary Plants Enhance the Presence of Natural Enemies of the Green Peach Aphid (Hemiptera: Aphididae) in Mediterranean Peach Orchards?
Conservation biological control could be an alternative to insecticides for the management of the aphid Myzus persicae (Sulzer). To develop sustainable strategies for M. persicae control in peach orchards in the Mediterranean, a 2-yr field experiment was conducted to identify the key predators of the aphid; to determine whether the proximity of insectary plants boost natural enemies of M. persicae in comparison to the resident vegetation; and whether selected insectary plants enhance natural enemy populations in the margins of peach orchards. Aphidoletes aphidimyza Rondani (Diptera: Cecidomyiidae) and Episyrphus balteatus De Geer (Diptera: Syrphidae) were the most abundant predators found among sentinel aphid colonies, accounting for 57% and 26%, respectively. Samplings during 2015 yielded twice as many hoverflies in M. persicae sentinel plants close to the insectary plants as those close to the resident vegetation. The abundance of other natural enemies in sentinel plants, depending on their proximity to the insectary plants, was not significantly different in either of the 2 yr. Hoverflies hovered more often over the insectary plants than over the resident vegetation and landed significantly more often on Lobularia maritima (L.) Desv., Moricandia arvensis (L.) DC., and Sinapis alba L. (Brassicales: Brassicaceae) than on Achillea millefollium L. (Asterales: Compositae). Parasitoids were significantly more abundant in L. maritima and A. millefollium. The vicinity of selected insectary plants to peach orchards could improve the presence of hoverflies, which might benefit the biological control of M. persicae.


Kruppel-like factor 14 ameliorated obesity and related metabolic disorders by promoting adipose tissue browning.
Obesity has been identified as a serious and debilitating disease that threatens human health, but the current treatment strategies still have some shortcomings. Exercise and dieting are difficult for many people to adhere to, and a series of surgical risks and pain brought about by volume reduction have made it difficult for the current weight loss effect to meet human expectations. In this study, we first found that mice with overexpression of the transcription factor Kruppel-like factor 14 (KLF14) in subcutaneous adipose tissue gained weight more slowly while consuming a high-fat diet than did control mice, and these mice also showed reduced insulin resistance and liver lipid deposition abnormalities. Mechanistically, the browning of white adipose tissue was promoted in adipose tissue with KLF14 overexpression; therefore, we preliminarily concluded that KLF14 can improve obesity by promoting the browning of white adipose tissue and energy consumption, thus ameliorating obesity and related metabolic disturbances. In summary, our results revealed that KLF14 may promote white adipose tissue browning, thus ameliorating high-fat diet-induced obesity and hepatic steatosis, as well as serum lipid levels and insulin resistance, thereby achieving a positive effect on metabolism.NEW & NOTEWORTHY Our study first explored the role of KLF14 in the development and progression of HFD-induced obesity in male mice. Its beneficial effect on adipose browning and metabolic disorders suggests that KLF14 may provide us a new therapeutic strategy for obesity and related metabolic complications. This health problem is of global concern and needs to be addressed.


Quality control processes in allografting: A twenty-year retrospective review of a hospital-based bone bank in Taiwan.
Musculoskeletal allografts are now commonly used. To decrease the potential risks of transmission of pathogenic bacteria, fungi, or viruses to the transplant recipients, certain issues regarding the management of patients who receive contaminated allografts need to be addressed. We aimed to clarify the incidence and extent of disease transmission from allografts by analyzing the allografting procedures performed in the bone bank of our hospital over the past 20 years. We retrospectively reviewed the data from our allograft registry center on 3979 allografts that were implanted in 3193 recipients throughout a period of two decades, from July 1991 to June 2011. The source of the allografts, results of all screening tests, dates of harvesting and implantation, and recipients of all allografts were checked. With the help of the Center for Infection Control of our hospital, a strict prospective, hospital-wide, on-site surveillance was conducted, and every patient with healthcare-associated infection was identified. Fisher's exact test was used to compare the infection rate between recipients with sterile allografts and those with contaminated allografts. The overall discard and infection rates were, respectively, 23% and 1.3% in the first decade (1991-2001); and 18.4% and 1.25% in the second decade (2001-2011). The infection rate of contaminated allograft recipients was significantly higher than that of sterile allograft recipients (10% vs. 1.15%, P < 0.01) in the second decade. Both infection and discard rates of our bone bank are comparable with those of international bone banks. Strict allograft processing and adequate prophylactic use of antibiotics are critical to prevent infection and disease transmission in such cases.


Ecology of Lyme disease.
Borrelia burgdorferi is transmitted from wild animals to humans by the bite of Ixodes dammini. This tick is common in many areas of southern Connecticut where it parasitizes three different host animals during its two-year life cycle. Larval and nymphal ticks have parasitized 31 different species of mammals and 49 species of birds. White-tailed deer (Odocoileus virginianus) appear to be crucial hosts for adult ticks. All three feeding stages of the tick parasitize humans, though most infections are acquired from feeding nymphs in May through early July. Reservoir hosts for the spirochete include rodents, other mammals, and even birds. White-footed mice (Peromyscus leucopus) are particularly important reservoirs, and in parts of southern Connecticut where Lyme disease is prevalent in humans, borreliae are universally present during the summer in these mice. Prevalence of infected ticks has ranged from 10-35%. Isolates of B. burgdorferi from humans, rodents, and I. dammini are usually indistinguishable, but strains of B. burgdorferi with different major proteins have been identified.


CD248 promotes insulin resistance by binding to the insulin receptor and dampening its insulin-induced autophosphorylation.
In spite of new treatments, the incidence of type 2 diabetes (T2D) and its morbidities continue to rise. The key feature of T2D is resistance of adipose tissue and other organs to insulin. Approaches to overcome insulin resistance are limited due to a poor understanding of the mechanisms and inaccessibility of drugs to relevant intracellular targets. We previously showed in mice and humans that CD248, a pre/adipocyte cell surface glycoprotein, acts as an adipose tissue sensor that mediates the transition from healthy to unhealthy adipose, thus promoting insulin resistance. Molecular mechanisms by which CD248 regulates insulin signaling were explored using in vivo insulin clamp studies and biochemical analyses of cells/tissues from CD248 knockout (KO) and wild-type (WT) mice with diet-induced insulin resistance. Findings were validated with human adipose tissue specimens. Genetic deletion of CD248 in mice, overcame diet-induced insulin resistance with improvements in glucose uptake and lipolysis in white adipose tissue depots, effects paralleled by increased adipose/adipocyte GLUT4, phosphorylated AKT and GSK3β, and reduced ATGL. The insulin resistance of the WT mice could be attributed to direct interaction of the extracellular domains of CD248 and the insulin receptor (IR), with CD248 acting to block insulin binding to the IR. This resulted in dampened insulin-mediated autophosphorylation of the IR, with reduced downstream signaling/activation of intracellular events necessary for glucose and lipid homeostasis. Our discovery of a cell-surface CD248-IR complex that is accessible to pharmacologic intervention, opens research avenues toward development of new agents to prevent/reverse insulin resistance. Funded by Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada (NSERC), Canada Foundations for Innovation (CFI), the Swedish Diabetes Foundation, Family Ernfors Foundation and Novo Nordisk Foundation.


Impact of the COVID-19 Pandemic on the Clinical Learning Environment: Addressing Identified Gaps and Seizing Opportunities.
The clinical learning environment (CLE) encompasses the learner's personal characteristics and experiences, social relationships, organizational culture, and the institution's physical and virtual infrastructure. During the COVID-19 pandemic, all 4 of these parts of the CLE have undergone a massive and rapid disruption. Personal and social communications have been limited to virtual interactions or shifted to unfamiliar clinical spaces because of redeployment. Rapid changes to the organizational culture required prompt adaptations from learners and educators in their complex organizational systems yet caused increased confusion and anxiety among them. A traditional reliance on a physical infrastructure for classical educational practices in the CLE was challenged when all institutions had to undergo a major transition to a virtual learning environment. However, disruptions spurred exciting innovations in the CLE. An entire cohort of physicians and learners underwent swift adjustments in their personal and professional development and identity as they rose to meet the clinical and educational challenges they faced due to COVID-19. Social networks and collaborations were expanded beyond traditional institutional walls and previously held international boundaries within multiple specialties. Specific aspects of the organizational and educational culture, including epidemiology, public health, and medical ethics, were brought to the forefront in health professions education, while the physical learning environment underwent a rapid transition to a virtual learning space. As health professions education continues in the era of COVID-19 and into a new era, educators must take advantage of these dynamic systems to identify additional gaps and implement meaningful change. In this article, health professions educators and learners from multiple institutions and specialties discuss the gaps and weaknesses exposed, opportunities revealed, and strategies developed for optimizing the CLE in the post-COVID-19 world.


Ecological networks: delving into the architecture of biodiversity.
In recent years, the analysis of interaction networks has grown popular as a framework to explore ecological processes and the relationships between community structure and its functioning. The field has rapidly grown from its infancy to a vibrant youth, as reflected in the variety and quality of the discussions held at the first international symposium on Ecological Networks in Coimbra-Portugal (23-25 October 2013). The meeting gathered 170 scientists from 22 countries, who presented data from a broad geographical range, and covering all stages of network analyses, from sampling strategies to effective ways of communicating results, presenting new analytical tools, incorporation of temporal and spatial dynamics, new applications and visualization tools.(1) During the meeting it became evident that while many of the caveats diagnosed in early network studies are successfully being tackled, new challenges arise, attesting to the health of the discipline.


Paranasal sinusitis in burn patients following nasotracheal intubation.
Paranasal sinusitis is a complication of nasotracheal intubation. Of 99 nasally intubated adult patients who survived 48 hours after being burned, 22 who were intubated for more than 7 days underwent a computed tomographic scan of all paranasal sinuses, with timing dictated by the patient's clinical condition. Eight patients had computed tomographic and clinical findings consistent with sinusitis. Treatment consisted of removal of all nasal tubes, oral and topical nasal decongestants, and, when appropriate, culture-specific antibiotics. A subgroup of patients with preexisting sinus disease made up 50% of the patients with sinusitis; early conversion to an oral airway or a tracheostomy should be considered in such patients. Only one patient required surgical drainage of the sinuses. The frequency and morbidity of sinusitis in nasotracheally intubated burn patients does not justify the risk of routine conversion to an oral airway.


Single-cell imaging of human cancer xenografts using adult immunodeficient zebrafish.
Zebrafish are an ideal cell transplantation model. They are highly fecund, optically clear and an excellent platform for preclinical drug discovery studies. Traditionally, xenotransplantation has been carried out using larval zebrafish that have not yet developed adaptive immunity. Larval engraftment is a powerful short-term transplant platform amenable to high-throughput drug screening studies, yet animals eventually reject tumors and cannot be raised at 37 °C. To address these limitations, we have recently developed adult casper-strain prkdc-/-, il2rgα-/- immunocompromised zebrafish that robustly engraft human cancer cells for in excess of 28 d. Because the adult zebrafish can be administered drugs by oral gavage or i.p. injection, our model is suitable for achieving accurate, preclinical drug dosing. Our platform also allows facile visualization of drug effects in vivo at single-cell resolution over days. Here, we describe the procedures for xenograft cell transplantation into the prkdc-/-, il2rgα-/- model, including refined husbandry protocols for optimal growth and rearing of immunosuppressed zebrafish at 37 °C; optimized intraperitoneal and periocular muscle cell transplantation; and epifluorescence and confocal imaging approaches to visualize the effects of administering clinically relevant drug dosing at single-cell resolution in vivo. After identification of adult homozygous animals, this procedure takes 35 d to complete. 7 days are required to acclimate adult fish to 37 °C, and 28 d are required for engraftment studies. Our protocol provides a comprehensive guide for using immunocompromised zebrafish for xenograft cell transplantation and credentials the model as a new preclinical drug discovery platform.


Noisy waters can influence young-of-year lobsters' substrate choice and their antipredatory responses.
Offshore human activities lead to increasing amounts of underwater noise in coastal and shelf environments, which may affect commercially-important benthic invertebrate groups like the re-stocked Helgoland European lobster (Homarus gammarus) in the German Bight (North Sea). It is crucial to understand the impact tonal low-frequency noises, like maritime transport and offshore energy operations, may have on substrate choice and lobsters' behavior to assess potential benefits or bottlenecks of new hard-substrate artificial offshore environments that become available. In this study, we investigated the full factorial effect of a tonal low-frequency noise and predator presence on young-of-year (YOY) European lobsters' in a diurnal and nocturnal experiment. Rocks and European oyster shells (Ostrea edulis) were offered as substrate to YOY lobsters for 3 h. Video recordings (n = 134) allowed the identification of lobsters' initial substrate choice, diel activity and key behaviors (peeking, shelter construction, exploration and hiding). To ensure independence, YOY lobsters in the intermolt stage were randomly selected and assigned to the experimental tanks and used only once. We provide the first evidence that stressors alone, and in combination, constrain YOY lobsters' initial substrate choice towards rocks. During nighttime, the joint effect of exposure to a constant low-frequency noise and predator presence decreased antipredator behavior (i.e., hiding) and increased exploration behavior. Noise may thus interfere with YOY lobsters' attention and decision-making processes. This outcome pinpoints that added tonal low-frequency noise in the environment have the potential to influence the behavior of early-life stages of European lobsters under predator pressure and highlights the importance of including key benthic invertebrates' community relationships in anthropogenic noise risk assessments. Among others, effects of noise must be taken into consideration in plans involving the multi-use of any offshore area for decapods' stock enhancement, aquaculture, and temporary no-take zones.


Novel natural immunogenic peptides from Numb1 and Notch1 proteins for CD8+ cells in ovarian ascites.
Notch is a plasma membrane receptor involved in the control of cell fate specification and in the maintenance of the balance between proliferation and differentiation in many cell lineages. Disruption of Notch has been implicated in a variety of hematological and solid cancers. Numb is also expressed in many adult mammalian cells. Adult cells divide symmetrically, and Numb is symmetrically partitioned at mitosis. The Numb-mediated regulation of Notch is believed to play a causative role in naturally occurring breast cancers. Reduction of Numb levels in breast tumors is regulated by proteasomal degradation. We reasoned that if the disregulated negative control of Notch by Numb protein is the consequence of Numb proteasomal degradation, then degradation of Numb can generate peptides which are transported, presented by MHC-I molecules. Surprisingly we found few candidate naturally processed peptides from Notch1, Notch2, and Numb1. CD8+ T cells expressing TCRs which specifically recognized peptides Notch1 (2112-2120) and Numb1 (87-95) were presented in the ascites of ovarian cancer patients. Many of these cells were differentiated and expressed high levels of Perforin. The natural immunogenicity of Notch1 and particularly of Numb1 suggests a mechanism of immunosurveillance which is overcome during tumor progression. Immunotherapy with tumor antigens from Notch and Numb should be important for treatment of cancer patients.


Molecular mechanisms controlling sensitivity to toxic metal ions in yeast.
Contamination of the environment has made toxic metal ions a major health issue. The use of yeasts as model systems for the identification of molecular mechanisms that control sensitivity to these agents is particularly attractive because of the ease of genetic manipulation and the availability of the complete Saccharomyces cerevisiae genomic sequence. This paper reviews information on those genes and mechanisms that have been identified in both the budding yeast S. cerevisiae and the fission yeast Schizosaccharomyces pombe as being capable of modulating sensitivity to important toxic metals. The factors that influence sensitivity to toxic metal ions include cellular thiols (glutathione, phytochelatins, labile sulfide, and metallothioneins) and the products of genes directly and indirectly involved in the transport or sequestration of the metal ion. A complete understanding of the molecular basis of sensitivity to toxic metal ions in lower organisms is expected to provide useful insights in the metal ion detoxification pathways and diseases related to these pathways in humans.


Effect of neuraminidase treatment of cells and effect of soluble glycoproteins on type 3 reovirus attachment to murine L cells.
The effect of pretreatment of murine L cells with bacterial neuraminidases on type 3 reovirus attachment was examined. We observed that such treatments resulted in a 60 to 80% decrease of subsequent attachment of 35S-labeled type 3 reovirus in a time- and dose-dependent manner. This result was specific for removal of cell surface sialic acid residues since the specific neuraminidase inhibitor 2-deoxy-2,3-dehydro-n-acetyl neuraminic acid completely prevented the observed effect. Although the total amount of radiolabeled virus bound to neuraminidase-treated cells was greatly reduced, unlabeled reovirus competed only slightly less efficiently for the attachment of 35S-labeled reovirus to neuraminidase-treated versus mock-treated L cells, suggesting that the specificity of the virus interaction with cellular receptor sites was only slightly diminished. Saturation experiments with mock-treated cells or with cells treated with Vibrio cholerae or with V. cholerae plus Arthrobacter ureafaciens neuraminidases indicated that the number of specific cellular receptor sites for type 3 reovirus were reduced by about 47%. We determined that under the neuraminidase digestion conditions used in this experiment we were able to remove a maximum 75% of the total N-acetylneuraminic acid of L cells. Our results also demonstrated that glycoproteins bearing a large amount of sialic acid containing oligosaccharides as well as purified N-acetylneuraminic acid, N-glycolylneuraminic acid, and N-acetylneuraminyl lactose were inhibitors of attachment, while proteins containing no sialic acid or negligible amounts of sialic acid did not inhibit attachment. High concentrations of various monosaccharides and lactose had no effect on reovirus attachment, in agreement with the recent results of Armstrong and his collaborators (Armstrong et al., Virology, 138:37-48, 1984). These data are also supported by the observation that gangliosides are inhibitors of viral attachment (Armstrong et al., Virology, 138:37-48, 1984). Taken together, our results suggest that cell surface sialic acid-containing glycoconjugates are involved in type 3 reovirus binding to murine L cells.


Antimicrobial drug resistance among clinically relevant bacterial isolates in sub-Saharan Africa: a systematic review.
Little is known about the prevalence of antimicrobial resistance (AMR) amongst bacterial pathogens in sub-Saharan Africa (sSA), despite calls for continent-wide surveillance to inform empirical treatment guidelines. We searched PubMed and additional databases for susceptibility data of key pathogens for surveillance, published between 1990 and 2013. Extracted data were standardized to a prevalence of resistance in populations of isolates and reported by clinical syndrome, microorganism, relevant antimicrobial drugs and region. We identified 2005 publications, of which 190 were analysed. Studies predominantly originated from east sSA (61%), were hospital based (60%), were from an urban setting (73%) and reported on isolates from patients with a febrile illness (42%). Quality procedures for susceptibility testing were described in <50% of studies. Median prevalence (MP) of resistance to chloramphenicol in Enterobacteriaceae, isolated from patients with a febrile illness, ranged between 31.0% and 94.2%, whilst MP of resistance to third-generation cephalosporins ranged between 0.0% and 46.5%. MP of resistance to nalidixic acid in Salmonella enterica Typhi ranged between 15.4% and 43.2%. The limited number of studies providing prevalence data on AMR in Gram-positive pathogens or in pathogens isolated from patients with a respiratory tract infection, meningitis, urinary tract infection or hospital-acquired infection suggested high prevalence of resistance to chloramphenicol, trimethoprim/sulfamethoxazole and tetracycline and low prevalence to third-generation cephalosporins and fluoroquinolones. Our results indicate high prevalence of AMR in clinical bacterial isolates to antimicrobial drugs commonly used in sSA. Enhanced approaches for AMR surveillance are needed to support empirical therapy in sSA.


Evaluation of head and neck cancer education at European dental schools.
In Europe, approximately 150.000 patients are diagnosed with head and neck cancer annually. Dentists play an important role in prevention and detection at an early stage when survival rates are best. This study aims to evaluate content of head and neck cancer education curricula of European dental schools. A questionnaire, comprising 20 questions about content of curricula and teaching methods, was distributed to the deans of all 234 members of the Association for Dental Education in Europe. The response rate was 24%. All dental schools included head and neck cancer screening practices in their curricula, two-thirds had their students perform this screening on all patients routinely and education was mostly divided over various courses (65%). A variation in content of education in screening practices and counselling patients about various risk factors was reported. Alcohol and tobacco use were included in most curricula as risk factors for head and neck cancer (98%), gastro-oesophageal reflux was less frequently included (41%). The human papillomavirus (HPV) as a risk factor for oropharyngeal cancer was included in 94% of curricula and 87% also contained education about strategies to discuss prevention of HPV-related cancer. No association was found between curricula containing strategies about discussing HPV-related cancer and inclusion of the HPV vaccine in national immunisation programmes. Head and neck cancer teaching programmes show a considerable variation across European dental schools. Development of a unified teaching programme suitable for all European dental schools seems warranted.


Barriers and Drivers Regarding the Use of Mobile Health Apps Among Patients With Type 2 Diabetes Mellitus in the Netherlands: Explanatory Sequential Design Study.
Self-monitoring of blood glucose levels, food intake, and physical activity supports self-management of patients with type 2 diabetes mellitus (T2DM). There has been an increase in the development and availability of mobile health apps for T2DM. The aim of this study is to explore the actual use of mobile health apps for diabetes among patients with T2DM and the main barriers and drivers among app users and nonusers. An explanatory sequential design was applied, starting with a web-based questionnaire followed by semistructured in-depth interviews. Data were collected between July and December 2020. Questionnaire data from 103 respondents were analyzed using IBM SPSS Statistics (version 25.0). Descriptive statistics were performed for the actual use of apps and items of the Unified Theory of Acceptance and Use of Technology (UTAUT). The UTAUT includes 4 key constructs: performance expectancy (the belief that an app will help improve health performance), effort expectancy (level of ease associated with using an app), social influence (social support), and facilitating conditions (infrastructural support). Differences between users and nonusers were analyzed using chi-square tests for individual items. Independent 2-tailed t tests were performed to test for differences in mean scores per the UTAUT construct. In total, 16 respondents participated in the interviews (10 users and 6 nonusers of apps for T2DM). We performed content analysis using a deductive approach on all transcripts, guided by the UTAUT. Regarding actual use, 55.3% (57/103) were nonusers and 44.7% (46/103) were users of apps for T2DM. The main driver for the use of apps was the belief that using apps for managing diabetes would result in better personal health and well-being. The time and energy required to keep track of the data and understand the app were mentioned as barriers. Mean scores were significantly higher among users compared with nonusers of apps for T2DM for the constructs performance expectancy (4.06, SD 0.64 vs 3.29, SD 0.89; P<.001), effort expectancy (4.04, SD 0.62 vs 3.50, SD 0.82; P<.001), social influence (3.59, SD 0.55 vs 3.29, SD 0.54; P=.007), and facilitating conditions (4.22, SD 0.48 vs 3.65, SD 0.70; P<.001). On the basis of 16 in-depth interviews, it was recognized that health care professionals play an important role in supporting patients with T2DM in using apps. However, respondents noticed that their health care professionals were often not supportive of the use of apps for managing diabetes, did not show interest, or did not talk about apps. Reimbursement by insurance companies was mentioned as a missing facilitator. Empowering health care professionals' engagement is of utmost importance in supporting patients with T2DM in the use of apps. Insurance companies can play a role in facilitating the use of diabetes apps by ensuring reimbursement.


Microbial biosurfactants: Multifarious applications in sustainable agriculture.
Agriculture in the 21st century faces grave challenges to meet the unprecedented food demand of the burgeoning population as well as reduce the ecological footprint for achieving sustainable development goals. The extensive use of harsh synthetic surfactants in pesticides and the agrochemical industry has substantial adverse impacts on the soil and environment due to their toxic and non-biodegradable nature. Biosurfactants derived from plant, animal, and microbial sources can be an eco-friendly alternative to chemical surfactants. Microbes producing biosurfactants play a noteworthy role in biofilm formation, plant pathogen elimination, biodegradation, bioremediation, improving nutrient bioavailability, and can thrive well under stressful environments. Microbial biosurfactants are well suited for heavy metal and organic contaminants remediation in agricultural soil due to their low toxicity, high activity at fluctuating temperatures, biodegradability, and stability over a wide array of environmental conditions. This green technology will improve the agricultural soil quality by increasing the soil flushing efficiency, mobilization, and solubilization of nutrients by forming metal-biosurfactant complexes, and through the dissemination of complex nutrients. Such characteristics help it to play a pivotal role in environmental sustainability in the foreseeable future, which is required to increase the viability of biosurfactants for extensive commercial uses, making them accessible, affordable, and economically sustainable.


Donation after circulatory death and lung transplantation.
Lung transplantation is the most effective modality for the treatment of patients with end-stage lung diseases. Unfortunately, many people cannot benefit from this therapy due to insufficient donor availability. In this review and update article, we discuss donation after circulatory death (DCD), which is undoubtedly essential among the strategies developed to increase the donor pool. However, there are ethical and legislative considerations in the DCD process that are different from those of donation after brain death (DBD). Among others, the critical aspects of DCD are the concept of the end of life, cessation of futile treatments, and withdrawal of life-sustaining therapy. In addition, this review describes a rationale for using lungs from DCD donors and provides some important definitions, highlighting the key differences between DCD and DBD, including physiological aspects pertinent to each category. The unique ability of lungs to maintain cell viability without circulation, assuming that oxygen is supplied to the alveoli-an essential aspect of DCD-is also discussed. Furthermore, an updated review of the clinical experience with DCD for lung transplantation across international centers, recent advances in DCD, and some ethical dilemmas that deserve attention are also reported.


Differential expression of phospholipase D isozymes in the hippocampus following kainic acid-induced seizures.
To investigate the pathophysiological role of phospholipase D (PLD)-mediated signaling, changes in the expression of the PLD isozymes PLD1 and PLD2 were investigated in the rat kainic acid (KA) model of human temporal lobe epilepsy. Western blot analysis showed a significant increase in the expression of PLD1 and PLD2 in the postictal hippocampus. PLD1 immunoreactivity increased preferentially in the CA3 and CA1 regions, where pyramidal neurons are susceptible to temporal lobe epilepsy. Experiments employing double immunofluorescence revealed that the cells expressing PLD1 were GFAP-expressing reactive astrocytes. By contrast, PLD2 immunoreactivity increased strikingly in infrapyramidal, but not in suprapyramidal granule cells of the postictal dentate gyrus, fitting well with results of the PLD activity assay. Considering that PLD belongs to a key signaling pathway, this result suggests that changes in granule cell activity in the dentate gyrus after seizures occurs specifically between the supra- and infrapyramidal blades. In addition, enhanced immunoreactivity of PLD2 was observed in the reactive astrocytes of the CA1, CA3, and hilar subregions, but its temporal pattern is different from that of PLD1. Taken together, our results suggest that PLD1 and PLD2 exercise their unique pathophysiological functions in the rat hippocampus after KA-induced seizures.


Responsibilities and rights in the promotion of health: differing positions of the individual and the state.
Medicine is the practice of humanitarianism. Its purpose should be to help others with benevolence and love. One must not think of one's own interest but should save and help the people who were created by Heaven and Earth (Veatch R. M. A. Theory of Medical Ethics, New York: Basic Books, 1981) [1].


Upregulation of CD44 expression in the retina during the rds degeneration.
In adult mouse retinas the standard form of the cell surface adhesion/receptor molecule CD44 is localized to Müller cell apical microvilli. In the rds (retinal degeneration slow) mouse, however, CD44 immunolabel is increased and distributed throughout the retina by 3 months postnatal. At present, it is unclear if this labeling pattern is due to the increased expression of standard CD44, the expression of variant CD44 isoforms, or an unmasking of CD44 antigenic sites. To further characterize this response, we have studied the expression of CD44 mRNA and protein in rds retinas of different ages. RT-PCR analysis demonstrated one product which represented the message for standard CD44 in adult BALB/c mouse retina and in all ages of rds retinas studied. Upon Southern blotting, this major product was detected along with two minor bands of larger size in all samples. Northern blot analysis demonstrated a major transcript of approximately 4.0 kb and a minor one of 3.0 kb in all BALB/c and rds retinas. By 3 months postnatal in rds retinas, the expression of CD44 message was increased by at least two-fold. Western blot analysis demonstrated the presence of only the standard form of CD44 protein in all BALB/c and rds retinas. An increased amount of this standard CD44 protein was observed in 2, 3, and 6 month rds retinas. Thus, this study demonstrates that the inherited retinal degeneration exhibited by the rds mouse does not cause an altered expression of retinal CD44 isoforms, but does lead to an upregulation in the expression of mRNA and protein for standard CD44.


Intra-abdominal desmoplastic small round cell tumor.
Intra-abdominal desmoplastic small round cell tumor is a rare malignancy with a predilection for young males. Unique histological and immunocytochemical features distinguish the tumor from other members of the family of small round cell tumors of infancy and childhood. The aggressive nature of tumor spread, relative insensitivity to chemotherapy, and generally incomplete resectability result in a very poor prognosis. The authors report a case of a 39-year-old man with diffuse abdominal and pelvic involvement of intra-abdominal desmoplastic small round cell tumor treated with aggressive chemotherapy and surgery. Computed tomography (CT)-guided biopsy of an omental mass was performed. Histologically, discrete nests of uniform closely packed malignant cells were distributed in a background of focally desmoplastic stroma. Immunocytochemistry demonstrated positivity for epithelial, mesenchymal, and neural markers. On the basis of these unique histological and immunohistochemical characteristics, the diagnosis of desmoplastic small round cell tumor was made. The patient was treated with aggressive neoadjuvant chemotherapy consisting of a high-dose alkylator -based combination regimen, followed by surgery. The patient had a 10 to 15 percent regression in tumor mass in response to chemotherapy. Laparotomy revealed two large omental masses, another large mass adherent to the left colon and pelvic sidewall, and diaphragmatic, peritoneal and mesenteric studding with small nodules. Complete surgical resection was not possible. Intra-abdominal desmoplastic small round cell tumor remains an aggressive malignancy with an extremely poor prognosis. Although some response to chemotherapy may be possible, complete resection is rare, and surgical efforts are generally palliative.


Hydrogen sulfide alleviates myocardial fibrosis in mice with alcoholic cardiomyopathy by downregulating autophagy.
Myocardial fibrosis is one of the most important pathological features of alcoholic cardiomyopathy (ACM). Hydrogen sulfide (H2S) exerts protective effects in various types of cardiovascular disease, which has been demonstrated by many previous studies. However, there is a lack of adequate research on the effect of H2S on myocardial fibrosis in ACM. The present study aimed to investigate the etiopathogenic role of H2S in myocardial fibrosis induced by chronic alcohol intake. An ACM mouse model was induced by consumption of 4% ethanol solution in drinking water for 12 weeks. Sodium hydrosulfide (NaHS) was used as a donor to provide exogenous H2S. Twelve weeks later, mice were sacrificed to calculate the heart to body weight ratio. The degree of myocardial collagen deposition was evaluated by Masson's and Van Gieson's staining, the expression level of collagen Ⅰ was measured by immunohistochemistry and autophagosomes were observed by transmission electron microscopy. In addition, the expression levels of autophagy‑associated proteins and fibrosis-associated proteins were detected by western blotting, and the expression levels of miR-21 and miR-211 were detected by reverse transcription-quantitative polymerase chain reaction. The outcomes of the study revealed that chronic alcohol intake results in myocardial fibrosis, enhanced myocardial collagen deposition and increased expression levels of collagen I, autophagy, autophagy-associated proteins (Beclin 1, Atg3 and Atg7) and fibrosis-associated proteins (MMP8, MMP13, MMP14, MMP17 and TGF-β1), as well as miR-21 and miR-221. These results were markedly reversed following treatment with H2S. The present study confirmed that H2S relieves myocardial fibrosis in mice with ACM, and the underlying mechanism may involve the downregulation of autophagy and miR-21 and miR-211 expression levels.


Upper gastrointestinal tract polyps: what do we know about them?
This study aimed to evaluate upper gastrointestinal polyps detected during esophago- gastroduodenoscopy tests. We conducted a retrospective analysis on data regarding 55,987 upper gastrointestinal endoscopy tests performed at the endoscopy unit of Istanbul Education and Research Hospital between January 2006 and June 2012. A total of 66 upper gastrointestinal polyps from 59 patients were analyzed. The most common clinical symptom was dyspepsia, observed in 41 cases (69.5%). The localizations of the polyps were as follows: 29 in the antrum (43.9%), 15 in the corpus (22.7%), 11 in the cardia (16.7%), 3 in the fundus (4.54%), 3 in the second portion of the duodenum (4.54%), 2 in the bulbus (3.03%) and 3 in the lower end of the esophagus (4.54%). Histopathological types of polyps included hyperplastic polyps (44) (66.7%), faveolar hyperplasia (8) (12.1%), fundic gland polyps (4) (6.06%), squamous cell polyps (4) (6.06%), hamartomatous polyps (3) (4.54%), and pyloric gland adenoma (3) (4.54%). Histopathological analysis of the gastric mucosa showed chronic atrophic gastritis in 30 cases (50.84%), HP infection in 33 cases (55.9%) and intestinal metaplasia in 19 cases (32.20%). In 3 cases with multiple polyps, adenocarcinoma was detected in hyperplastic polyps. Among polypoid lesions of the upper gastrointestinal tract, the most common histological type is hyperplastic polyps. Generally, HP infection is associated with chronic atrophic gastritis and intestinal metaplasia. The incidence of adenocarcinoma tends to be higher in patients with multiple hyperplastic polyps.


Non-ST-Segment-Elevation Myocardial Infarction Among Patients With Chronic Kidney Disease: A Propensity Score-Matched Comparison of Percutaneous Coronary Intervention Versus Conservative Management.
Chronic kidney disease (CKD) remains an independent predictor of cardiovascular morbidity and mortality. CKD complicates referral for percutaneous coronary intervention (PCI) in non-ST-segment-elevation myocardial infarction (NSTEMI) patients because of the risk for acute kidney injury and the need for dialysis, with American College of Cardiology/American Heart Association guidelines underscoring the limited data on these patients. Using the National Inpatient Sample to analyze hospitalizations in the United States from 2004 to 2014, we sought to assess PCI utilization and in-hospital outcomes in NSTEMI admissions with CKD. NSTEMI admissions were identified by International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) code 410.7. CKD admissions were identified by ICD-9-CM code 585. Propensity score-matched cohorts of patients with NSTEMI were matched for age, sex, comorbidities, race, median household income, primary payer status, and hospital characteristics. Of 4 488 795 hospitalizations for NSTEMI, 31% underwent PCI. Overall, 89% of admissions had no CKD. In addition, 32% of NSTEMI admissions with no CKD and 23%, 14%, and 22% with CKD stages 3, 4, and 5 underwent PCI, respectively. Hospitalized NSTEMI patients with CKD stages 4 and 5 had 41% and 20% less likelihood, respectively, of undergoing PCI compared with those with no CKD. Among hospitalized NSTEMI patients with no CKD or CKD stage 3, 4, or 5, PCI-treated groups had 63%, 57%, 39%, and 59% lower likelihood, respectively, of all-cause, in-hospital mortality compared with propensity score-matched medically managed groups. PCI use decreased among hospitalized NSTEMI patients as CKD severity increased, and all-cause, in-hospital mortality was greater for NSTEMI patients admitted with more severe CKD regardless of treatment strategy.


Secondary organic aerosol formation via the isolation of individual reactive intermediates: role of alkoxy radical structure.
The study of the chemistry underlying secondary organic aerosol (SOA) formation is complicated by the large number of reaction pathways and oxidation generations available to a given precursor species. Here we simplify such complexity to that of a single alkoxy radical (RO), by forming SOA via the direct photolysis of alkyl nitrite (RONO) isomers. Chamber experiments were conducted with 11 C10 RONO isomers to determine how the position of the radical center and branching of the carbon skeleton influences SOA formation. SOA yields served as a probe of RO reactivity, with lower yields indicating that fragmentation reactions dominate and higher yields suggesting the predominance of RO isomerization. The largest yields were from straight-chain isomers, particularly those with radical centers located toward the terminus of the molecule. Trends in SOA yields can be explained in terms of two major effects: (1) the relative importance of isomerization and fragmentation reactions, which control the distribution of products, and (2) differences in volatility among the various isomeric products formed. Yields from branched isomers, which were low but variable, provide insight into the degree of fragmentation of the alkoxy radicals; in the case of the two β-substituted alkoxy radicals, fragmentation appears to occur to a greater extent than predicted by structure-activity relationships. Our results highlight how subtle differences in alkoxy radical structure can have major impacts on product yields and SOA formation.


Coronavirus Disease 2019 (COVID-19) and Venous Thromboembolism During Pregnancy and Postpartum.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased risk for macro- and micro-thrombi. Consensus guidelines recommend use of thromboprophylaxis in nonobstetric patients with SARS-CoV-2 infection admitted to the hospital. National-level studies evaluating venous thromboembolism (VTE) among pregnant and postpartum individuals with and without SARS-CoV-2 infection have not been completed. We performed a retrospective cohort study of individuals aged 18 years or older delivering at more than 20 weeks of gestation with data in the MarketScan Commercial Insurance Database from 2016 through 2020. Of 811,008 deliveries, SARS-CoV-2 infection during pregnancy or through 6 weeks postpartum was associated with increased risk for VTE compared with no infection (1.0% vs 0.5%, adjusted hazard ratio 2.62, 95% CI 1.60-4.29). Findings support further consideration of thromboprophylaxis in the obstetric population with SARS-CoV-2 infection.


Diphyllobothriosis--experimental study.
For the first time the agent of diphyllobothriosis Lake Baikal is the cestoda D. dendriticum establishted by T.P. Chizhova and P.G. Gofman-Kadoshnikov (1962). D. dendriticum reaches maturity in human intestine, but it is considered, that the relationships between the parasite and human are facultative property (Klebonovski 1985). The results of the investigation of the diet of sea-gull nestlings (control-uninfected and experimental-infected birds with cestoda groups) and stress influence (starvation) on the mass loss in experimentally and naturally infected ones with different duration conditions adaptation of experiments are discussed in this article.


Development of calcium phosphate-chitosan composites with improved removal capacity toward tetracycline antibiotic: Adsorption and electrokinetic properties.
Two eco-friendly and highly efficient adsorbents, namely brushite-chitosan (DCPD-CS), and monetite-chitosan (DCPA-CS) composites were synthesized via a simple and low-cost method and used for tetracycline (TTC) removal. The removal behavior of TTC onto the composite particles was studied considering various parameters, including contact time, pollutant concentration, and pH. The maximum TTC adsorption capacity was 138.56 and 112.48 mg/g for the DCPD-CS and DCPA-CS, respectively. Increasing the pH to 11 significantly enhanced the adsorption capacity to 223.84 mg/g for DCPD-CS and 205.92 mg/g for DCPA-CS. The antibiotic adsorption process was well-fitted by the pseudo-second-order kinetic and Langmuir isotherm models. Electrostatic attractions, complexation, and hydrogen bonding are the main mechanisms governing the TTC removal process. Desorption tests demonstrated that the (NH4)2HPO4 solution was the most effective desorbing agent. The developed composites were more efficient than DCPD and DCPA reference samples and could be used as valuable adsorbents of TTC from contaminated wastewater.


Surgery and Endometriosis.
Care of the endometriosis patient today can be complex and difficult. Once medical management has been exhausted and symptoms persist patients desire further treatment options. This chapter takes an evidence-based approach at discussion of patient surgcical options for treatment of endometriosis symptoms. Surgical techniques, success rates, patient satisfaction, and risks must be discussed and understood at depth before planning patient surgical intervention. This chapter provides reference to current surgical management options and symptom relief following those interventions.


Breast self-examination beliefs and practices, ethnicity, and health literacy: Implications for health education to reduce disparities.
This study aimed to quantitatively and qualitatively examine breast cancer screening practices, including breast self-examination (BSE), and health literacy among patients with chronic disease. A prospective, multi-method study conducted with a targeted purposive sample of 297 patients with diabetes and/or hypertension from four ethnic groups (Latino, Vietnamese, African American, White-American) at an urban community health center. A federally qualified health center in Western Massachusetts. In our four-year study, 297 participants completed cancer knowledge, beliefs, attitudes and screening utilization scales and measures of health literacy. In addition to survey data collection, we conducted in-depth interviews, focus groups, home visits, and chronic disease diaries (n=71). In focus groups, African American, Vietnamese and Latina participants offered interviewers an unprompted demonstration of BSE, reported regular BSE use at particular times of the month, and shared positive feelings about the screening method. In a sample where approximately 93% of women have had a mammogram, many also had performed BSE (85.2%). Women with adequate health literacy were more likely than those with inadequate health literacy to rely on it. Despite being positively inclined toward BSE, Vietnamese women, who had the lowest health literacy scores in our sample, were less likely to perform BSE regularly. BSE seemed to be an appealing self-care practice for many women in our study, but we conclude that proper BSE practices may not be reinforced equally across ethnic groups and among patients with low health literacy.


Catalyst-controlled Wacker-type oxidation: facile access to functionalized aldehydes.
The aldehyde-selective oxidation of alkenes bearing diverse oxygen groups in the allylic and homoallylic position was accomplished with a nitrite-modified Wacker oxidation. Readily available oxygenated alkenes were oxidized in up to 88% aldehyde yield and as high as 97% aldehyde selectivity. The aldehyde-selective oxidation enabled the rapid, enantioselective synthesis of an important pharmaceutical agent, atomoxetine. Finally, the influence of proximal functional groups on this anti-Markovnikov reaction was explored, providing important preliminary mechanistic insight.


Association of chromatin proteins high mobility group box (HMGB) 1 and HMGB2 with mitotic chromosomes.
High mobility group box (HMGB) 1 and 2 are two abundant nonhistone nuclear proteins that have been found in association with chromatin. Previous studies based on immunofluorescence analysis indicated that HMGB1 dissociates from chromosomes during mitosis. In the present work, HMGB1 and 2 subcellular localization was reinvestigated in living cells by using enhanced green fluorescent protein- and Discosome sp. red fluorescent protein-tagged proteins. Contrary to previous reports, HMGB1 and 2 were shown to be present under two forms in mitotic cells, i.e., free and associated with the condensed chromatin, which rapidly exchange. A detailed analysis of HMGB2 interaction with mitotic chromosomes indicated that two sites encompassing HMG-box A and B are responsible for binding. Importantly, this interaction was rapidly inactivated when cells were permeabilized or exposed to chemical fixatives that are widely used in immunodetection techniques. A comparable behavior was also observed for two proteins of the HMG-nucleosome binding (HMGN) group, namely, HMGN1 and HMGN2.


Exploring Major Flavonoid Phytochemicals from Nelumbo nucifera Gaertn. as Potential Skin Anti-Aging Agents: In Silico and In Vitro Evaluations.
Nelumbo nucifera Gaertn., an aquatic medicinal plant (Nelumbonaceae family), has a history of use in traditional medicine across various regions. Our previous study demonstrated the skin anti-aging potential of its stamen ethanolic extract by effectively inhibiting collagenase and tyrosinase enzymes. While the major constituents of this extract are well documented, there is a lack of research on the individual compounds' abilities to inhibit skin aging enzymes. Therefore, this study aimed to evaluate the anti-aging potential of the primary flavonoids found in N. nucifera using both in silico and in vitro approaches. Our initial step involved molecular docking to identify compounds with the potential to inhibit collagenase, elastase, and tyrosinase. Among the seven flavonoids studied, kaempferol-3-O-robinobioside (Kae-3-Rob) emerged as the most promising candidate, exhibiting the highest docking scores for three skin aging-related enzymes. Subsequent enzyme-based inhibition assays confirmed that Kae-3-Rob displayed robust inhibitory activity against collagenase (58.24 ± 8.27%), elastase (26.29 ± 7.16%), and tyrosinase (69.84 ± 6.07%). Furthermore, we conducted extensive 200-ns molecular dynamics (MD) simulations, revealing the stability of the complexes formed between Kae-3-Rob and each enzyme along the MD simulation time. MM/PBSA-based binding free energy calculations indicated the considerably stronger binding affinity of Kae-3-Rob for collagenase and tyrosinase compared to elastase, which was related to the greater percentage of hydrogen bond occupations. These computational findings were consistent with the relatively high inhibitory activity of Kae-3-Rob against collagenase and tyrosinase observed in our in vitro experiment. In conclusion, the results obtained from this comprehensive study suggest that Kae-3-Rob, a key flavonoid from N. nucifera, holds significant potential as a source of bioactive compounds for anti-aging cosmeceutical and other phytopharmaceutical application.


Increased binding of a hydrophobic, photolabile probe to Escherichia coli inversely correlates to membrane potential but not adenosine 5'-triphosphate levels.
We describe conditions for a quantitative determination of azidopyrene binding to Escherichia coli cells. In addition, we define conditions whereby irradiation of azidopyrene in the presence of cells leads to irreversible association of probe with cells. This is presumably due to the light-dependent generation of reactive nitrenes and subsequent incorporation of nitrenopyrene moieties into cellular components. These methods allowed us to determine that the amount of azidopyrene bound to cells was inversely correlated with the magnitude of the cellular membrane potential, but was not correlated with high or low adenosine 5-triphosphate levels per se. Cells bound more azidopyrene if the delta psi was low. Cell-bound azidopyrene was found to be entirely associated with the inner and outer membrane. We suggest that the decreased association of hydrophobic probes upon energization of whole cells reflects a rapid transition in structural properties of the cell envelope.


Effects of high-intensity training on muscle lactate transporters and postexercise recovery of muscle lactate and hydrogen ions in women.
The purpose of this study was to investigate the effects of high-intensity interval training (3 days/wk for 5 wk), provoking large changes in muscle lactate and pH, on changes in intracellular buffer capacity (betam(in vitro)), monocarboxylate transporters (MCTs), and the decrease in muscle lactate and hydrogen ions (H+) after exercise in women. Before and after training, biopsies of the vastus lateralis were obtained at rest and immediately after and 60 s after 45 s of exercise at 190% of maximal O2 uptake. Muscle samples were analyzed for ATP, phosphocreatine (PCr), lactate, and H+; MCT1 and MCT4 relative abundance and betam(in vitro) were also determined in resting muscle only. Training provoked a large decrease in postexercise muscle pH (pH 6.81). After training, there was a significant decrease in betam(in vitro) (-11%) and no significant change in relative abundance of MCT1 (96 +/- 12%) or MCT4 (120 +/- 21%). During the 60-s recovery after exercise, training was associated with no change in the decrease in muscle lactate, a significantly smaller decrease in muscle H+, and increased PCr resynthesis. These results suggest that increases in betam(in vitro) and MCT relative abundance are not linked to the degree of muscle lactate and H+ accumulation during training. Furthermore, training that is very intense may actually lead to decreases in betam(in vitro). The smaller postexercise decrease in muscle H+ after training is a further novel finding and suggests that training that results in a decrease in H+ accumulation and an increase in PCr resynthesis can actually reduce the decrease in muscle H+ during the recovery from supramaximal exercise.


The Effect of Exercise on the Skin Content of the Reduced Form of NAD and Its Response to Transient Ischemia and Reperfusion in Highly Trained Athletes.
Reduced nicotinamide adenine dinucleotide (NADH) is synthesized in the cellular nucleus, cytoplasm and mitochondria but oxidized into NAD+ almost exclusively in mitochondria. Activation of human skin by the 340 nm ultraviolet light triggers natural fluorescence at the light length of 460 nm, which intensity is proportional to the skin NADH content. This phenomenon is used by the Flow Mediated Skin Fluorescence (FMSF) which measures changes in the skin NADH content during transient ischemia and reperfusion. We examined the effects of exercise to exhaustion on the skin changes of NADH in response to 200 s forearm ischemia and reperfusion in 121 highly trained athletes (94 men and 27 women, long-distance running, triathlon, taekwondo, rowing, futsal, sprint running, fencing, and tennis). We found that exercise until exhaustion changes the skin content of NADH, modifies NADH turnover at rest, during ischemia and reperfusion in the most superficial living skin cells. Compared to the pre-exercise, there were significant increases in: mean fluorescence recorded during rest as the baseline value (B mean) (p < 0.001), the maximal fluorescence that increased above the baseline during controlled forearm ischemia (FImax) (p < 0.001, only in men), the minimal fluorescence after decreasing below the baseline during reperfusion (FRmin) (p < 0.001 men; p < 0.01 women) and the difference between B mean and FRmin (R min) (p < 0.01), and reductions in the difference between FImax and B mean (I max) (p < 0.001) and I max/IRampl ratio (CImax) (p < 0.001) after the incremental exercise test. There was no statistical difference between pre- and post-exercise the maximal range of the fluorescence change during ischemia and reperfusion (IRampl). In conclusion, exercise to exhaustion modifies the skin NADH content at rest, during ischemia and reperfusion as well as the magnitude of changes in the NADH caused by ischemia and reperfusion. Our findings suggest that metabolic changes in the skin NADH accompanying exercise extend beyond muscles and affect other cells and organs.


Parents' Understanding About Children's Bullying: Fall ConsumerStyles Survey, United States, 2017, 2018, and 2019.
The purpose of this study was to explore U.S. parents' and caregivers' understanding about children's bullying-what bullying is and how to address it. We analyzed 2017, 2018, and 2019 Fall ConsumerStyles online panel survey data from U.S. parents/caregivers of children ages 10 to 17 years (N = 1,516), including 20 items representing statements consistent or inconsistent with the bullying prevention evidence and best practices. Percentage of endorsement for each item and a summary measure of understanding about bullying were calculated. The association between low overall understanding about bullying and sociodemographic characteristics was explored. Most parents identified bullying as harmful (77%), repetitive (63%), and involving power imbalance (51%). At least half of parents answered 13 or more items (20 total) consistent with the bullying prevention evidence or best practices. Being male, non-Hispanic Black or Hispanic, having high school or less education, and small household size were associated with higher odds of low overall understanding about bullying. Awareness of parents' understanding about bullying and how to appropriately address it is vital for bullying prevention. Findings can inform the strategic development of bullying prevention health messages for parents.


High-density lipoprotein protects cardiomyocytes against necrosis induced by oxygen and glucose deprivation through SR-B1, PI3K, and AKT1 and 2.
The cardioprotective lipoprotein HDL (high-density lipoprotein) prevents myocardial infarction and cardiomyocyte death due to ischemia/reperfusion injury. The scavenger receptor class B, type 1 (SR-B1) is a high-affinity HDL receptor and has been shown to mediate HDL-dependent lipid transport as well as signaling in a variety of different cell types. The contribution of SR-B1 in cardiomyocytes to the protective effects of HDL on cardiomyocyte survival following ischemia has not yet been studied. Here, we use a model of simulated ischemia (oxygen and glucose deprivation, OGD) to assess the mechanistic involvement of SR-B1, PI3K (phosphatidylinositol-3-kinase), and AKT in HDL-mediated protection of cardiomyocytes from cell death. Neonatal mouse cardiomyocytes and immortalized human ventricular cardiomyocytes, subjected to OGD for 4 h, underwent substantial cell death due to necrosis but not necroptosis or apoptosis. Pretreatment of cells with HDL, but not low-density lipoprotein, protected them against OGD-induced necrosis. HDL-mediated protection was lost in cardiomyocytes from SR-B1-/- mice or when SR-B1 was knocked down in human immortalized ventricular cardiomyocytes. HDL treatment induced the phosphorylation of AKT in cardiomyocytes in an SR-B1-dependent manner. Finally, chemical inhibition of PI3K or AKT or silencing of either AKT1 or AKT2 gene expression abolished HDL-mediated protection against OGD-induced necrosis of cardiomyocytes. These results are the first to identify a role of SR-B1 in mediating the protective effects of HDL against necrosis in cardiomyocytes, and to identify AKT activation downstream of SR-B1 in cardiomyocytes.


Designing Online Courses: 12 Tips for Health Professions Educators.
This article was migrated. The article was marked as recommended. With the changes brought on by the public health concerns during the spring of 2020, face-to-face teaching was replaced by remote teaching in a rapid fashion. Learning management systems (LMSs) and video conferencing services were rapidly utilized to deliver online learning of previously in-person sessions. As the familiarity with remote teaching increases, designs of previously taught face-to-face courses will be revisited. Online teaching and learning provide great options for self-paced education in the dynamic environment of health professions education. Creative use of tools and collaborative web-based technology enables learner-centered pedagogy and the establishment of a community of learners. We offer practical tips for designing and implementing a generalized online course for health professions educators that appeal to diverse learners through meaningful use of different types of media.


[Effect of adaptation to high altitude on the state of electric cardiac stability and lipid peroxidation during catecholamine cardionecrosis in rats].
The change of electric cardiac stability parameters and LP in catecholamine cardio necrosis in rats simulated by prolonged injection of increasing doses of noradrenaline was studied in this work. It was established that noradrenaline injection in low-altitude (760 m) and high-altitude (3200 m) is accompanied by hypertrophy, microcirculation disturbances, ischemia and cardiomyocytes necrosis, ECS decrease, LP activation and decrease of enzymatic activity of antioxidant defense. ECS of animals adapted to high-altitude decreased less and their LP processes were more active with preservation of enzymatic activity of antioxidant defense.


Network Analysis of Common Genes and Transcriptional Factors between Celiac Disease and Inflammatory Bowel Diseases.
BACKGROUND Understanding the associations among different disorders remarkably improves their diagnosis and treatments. Celiac disease is the most complicated and prevalent form of immune-mediated diseases. On the other hand, inflammatory bowel diseases lead to inflammation of the intestine with an unknown cause. Although inflammatory bowel diseases have been often thought of as an autoimmune disorder, they can be triggered by whatever that can lead to the inflammation in the whole bowel. Henceforth, both aforementioned diseases are related to autoimmune attacks and cause a sort of inflammatory event, which exploring trade-off among them supposedly will lead to discovering important genes and, in turn, to the possible common therapeutic protocols. In the current study, we aimed to determine the correlation between the common genes in celiac disease and inflammatory bowel diseases. METHODS 314 and 851 genes correlated with celiac disease and inflammatory bowel diseases respectively extracted from DisGeNET were subjected to an in-silico data analysis framework to mine prognosticates genes and the associated pathways. RESULTS 149 shared genes between these diseases regulated by highlighted transcription factors NFKB1, IRF1, STAT1, HSF1, GATA3 were characterized as discriminating molecules, which by further screening were enriched in pathways mostly involved in apoptosis, T cell activation, and cytokine, chemokine, and interleukin signaling. CONCLUSION We observed that the identified common genes were associated with a wide range of pathogenic mechanisms underlying these diseases.


Thyrotoxicosis in northern Nigeria: a rare disease.
Four hundred and thirteen patients had surgery for large to giant goitres between January 1971 and December 1985. Twenty-three (5.7%) of this number had thyrotoxicosis; there were 19 females and 4 males. Thirteen patients presented with nodular goitre; 3 of them had exophthalmos and mild infiltrative dermopathy associated with thyroid nodules--the Marine Lenhart syndrome.


Decision Making in Patients With Metastatic Spine. The Role of Minimally Invasive Treatment Modalities.
Spine metastases affect more than 70% of terminal cancer patients that eventually suffer from severe pain and neurological symptoms. Nevertheless, in the overwhelming majority of the cases, a spinal metastasis represents just one location of a diffuse systemic disease. Therefore, the best practice for treatment of spinal metastases depends on many different aspects of an oncological disease, including the assessment of neurological status, pain, location, and dissemination of the disease as well as the ability to predict the risk of disease progression with neurological worsening, benefits and risks associated to treatment and, eventually, expected survival. To address this need for a framework and algorithm that takes all aspects of care into consideration, we reviewed available evidence on the multidisciplinary management of spinal metastases. According to the latest evidence, the use of stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) for spinal metastatic disease is rapidly increasing. Indeed, aggressive surgical resection may provide the best results in terms of local control, but carries a significant rate of post-surgical morbidity whose incidence and severity appears to be correlated to the extent of resection. The multidisciplinary management represents, according to current evidence, the best option for the treatment of spinal metastases. Noteworthy, according to the recent literature evidence, cases that once required radical surgical resection followed by low-dose conventional radiotherapy, can now be more effectively treated by minimally invasive spinal surgery (MISS) followed by spine SRS with decreased morbidity, improved local control, and more durable pain control. This combination allows also extending this standard of care to patients that would be too sick for an aggressive surgical treatment.


Hepatocellular carcinoma: an Asian perspective.
Hepatocellular carcinoma (HCC) is one of the most frequently occurring malignancies in Asia. The incidence exceeds 30 cases/100,000/year in the east Asian region. Worldwide, it accounts for almost 1 million deaths/year. The high incidence in Asia is due to the high prevalence of chronic viral hepatitis, mainly chronic hepatitis B. With the introduction of universal vaccination for hepatitis B in some Asian countries in the mid 1980s, some of these countries are experiencing a decline in the incidence of HCC. This probably underscores the point that HCC caused by hepatitis B is a malignancy preventable by vaccine. Due to the relative paucity of symptoms in the early stages and the rapid doubling time of the tumor, most HCCs are discovered late in advanced stages at presentation. Most Asian countries have adopted a screening program for patients at risk. Earlier and smaller HCCs are detected through such programs but these programs have yet to demonstrate improved patient survival. Physicians managing patients with HCC are faced with two main challenges, the malignancy itself and the underlying liver disease. The extent of the tumor and the existing liver function limits the therapeutic choices available. Hepatic resection remains the treatment of choice. However, the majority of patients present with nonresectable tumors. Transarterial chemoembolization, percutaneous ethanol injection and radiofrequency ablation are the other treatment modalities. In patients with small tumors (<5 cm) and poor liver function, liver transplant offers a viable treatment alternative. In summary, the risk factor for HCC in Asia is predominantly chronic hepatitis B. Universal vaccination against hepatitis B is likely to reduce the incidence. The prognosis and outcome of treatment remains poor with a 5-year survival of 35% for patients treated surgically and less than 10% for nonresectable tumors. Current management is aimed at earlier detection and more effective treatment of early HCC. In future, the challenge will be managing HCC in the premalignant stage.


Lifespan of mountain ranges scaled by feedbacks between landsliding and erosion by rivers.
An important challenge in geomorphology is the reconciliation of the high fluvial incision rates observed in tectonically active mountain ranges with the long-term preservation of significant mountain-range relief in ancient, tectonically inactive orogenic belts. River bedrock erosion and sediment transport are widely recognized to be the principal controls on the lifespan of mountain ranges. But the factors controlling the rate of erosion and the reasons why they seem to vary significantly as a function of tectonic activity remain controversial. Here we use computational simulations to show that the key to understanding variations in the rate of erosion between tectonically active and inactive mountain ranges may relate to a bidirectional coupling between bedrock river incision and landslides. Whereas fluvial incision steepens surrounding hillslopes and increases landslide frequency, landsliding affects fluvial erosion rates in two fundamentally distinct ways. On the one hand, large landslides overwhelm the river transport capacity and cause upstream build up of sediment that protects the river bed from further erosion. On the other hand, in delivering abrasive agents to the streams, landslides help accelerate fluvial erosion. Our models illustrate how this coupling has fundamentally different implications for rates of fluvial incision in active and inactive mountain ranges. The coupling therefore provides a plausible physical explanation for the preservation of significant mountain-range relief in old orogenic belts, up to several hundred million years after tectonic activity has effectively ceased.


The Biodiversity of the Genus Dictyota: Phytochemical and Pharmacological Natural Products Prospectives.
Although a broad variety of classes of bioactive compounds have already been isolated from seaweeds of the genus Dictyota, most different species are still chemically and biologically unexplored. Dictyota species are well-known brown seaweeds belonging to the Dictyotaceae (Phaeophyta). The phytochemical composition within the genus Dictyota has recently received considerable interest, and a vast array of components, including diterpenes, sesquiterepenes, sterols, amino acids, as well as saturated and polyunsaturated fatty acids, have been characterized. The contribution of these valued metabolites to the biological potential, which includes anti-proliferative, anti-microbial, antiviral, antioxidant, anti-inflammatory, and anti-hyperpigmentation activities, of the genus Dictyota has also been explored. Therefore, this is the most comprehensive review, focusing on the published literature relevant to the chemically and pharmacologically diverse biopharmaceuticals isolated from different species of the genus Dictyota during the period from 1976 to now.


Surgical management of malignant bone tumours.
Limb-salvage surgery has proved adequate in the management of malignant bone tumours. The goal of radical resection is to achieve local control with an appropriate surgical margin. Sixty-five cases of bone tumours have been managed by radical resection and suitable reconstruction by autologous fibular strut grafting. Single fibular grafting was attempted in the upper extremity and dual fibular grafting in the lower extremity. None had obvious evidence of secondary metastases at the time of surgery. out of 65 cases, 39 were sarcomatous lesions. Biplane Angiography had proved extremely useful in the exact delineation and appropriate resection of such lesions. Twenty two patients had complications - eight had local recurrence, three had deep infection needing amputation and eleven had multiple secondaries and died. It is suggested that in an Oncologically sound limb, salvage procedure with biological reconstruction should be attempted.


[10 years of innovation in the treatment of latent tuberculosis infection: a comparison between standard and short course therapies in directly observed therapy].
The main aim of the study is to compare the acceptance, adherence, tolerance and safety of short course therapies in comparison to a standard 9 month treatment for latent tuberculosis infection (LTBI) in directly observed therapy (DOT) and contrast this with previous results from a standard therapy in patient self-administered treatment. Retrospective longitudinal study carried out at a medium sized prison. Period of inclusion covers 10 years, from January 2000 to December 2009. The Centers for Disease Control and Prevention (CDC) inclusion and exclusion criteria were used, as well as the ones included in the Program for Tuberculosis Prevention and Control in the Prison Environment. 4 LTBI therapies according to the preference of the patient and possible interactions with other treatments were utilised. Therapy I consisted of isoniazid (H) in doses of 300 mg/day for 9 months (9H), therapy II with rifampicin for 2 months, twice a week, (2R2Z2) therapy III with rifampicin and isoniazid for 3 months (3RH) and therapy IV with rifampicin for four months (4R). Treatment was administered under strict DOT conditions by nursing staff. 902 patients were included, of which 810 accepted the treatment (89.90%), distributed as follows: 400 in the 9H therapy, and 410 with short course therapies (316 in the 2R2Z2, 82 in the 3RH therapy and 12 in the 4R therapy). 92 patients (10.20%) did not accept LTBI therapy, 271 patients (67.75%) concluded the LTBI treatment with 9H, and 314 (76.60%) with short courses. 232 patients (73.42%) concluded the 2R2Z2, 85.40% with the 3RH 70 therapy and 12 (100%) with the 4R treatment. 129 patients (32.25%) did not complete the LTBI 9H therapy (63 due to voluntary withdrawal, 35 due to adverse reactions, 26 for release or transfer, 2 for unknown reasons, 1 due to tuberculosis in a HIV-patient and 1 due to suicide). 96 patients (23.41%) did not conclude the short course therapies (36 due to voluntary withdrawal, 54 due to adverse reactions, 1 due to release or transfer, 3 for unknown reasons, 1 due to a psychotic episode, and 1 due to hepatitis of unknown aetiology). Significant differences could be discerned in the LTBI therapy conclusion rates when comparing the standard 9H and short course therapies. A greater, statistically significant, probability is observed with the short course therapies: p: 0.006; Odds Ration: 1.56 (LC95%: 1.14-2.12). This difference is a result of the 9H therapy presenting a greater number of voluntary withdrawals for no apparent reason (p: 0.002; OR: 2.03 [1.30-3.15]) and a greater number of withdrawals as a result of transfers to another prison or release (p<0.0001; OR 30.22 [4.07-224.29]), with no significant differences being found in withdrawals for adverse reactions between the 9H therapy and the short course treatments as a whole. The 2R2Z2 therapy shows a higher probability of withdrawals for adverse reactions (p: 0.006; OR: 1.87 [(1.21-2.88]) than the other therapies. Greater acceptance of initiating therapy was observed in all the DOT therapies. The 3RH, 2R2Z2 and 4R short course therapies favoured better adherence, with significantly lower ratios of withdrawal than the 9H therapy for the treatment of latent tuberculosis infection. Tolerance and safety of the short course therapies was very similar to the standard 9H treatment, with a significantly higher percentage of adverse reactions in the 2R2Z2 therapy in comparison to others. Our data backs up the safety and adherence of a short course 3RH therapy in DOT for treating latent tuberculosis infection and its preferential use in the prison environment in comparison to isoniazid due to the greater number of patients concluding treatment. The administration of LBTI therapy in DOT achieves a high percentage of acceptance and conclusion of treatments in prison, significantly improving on the previous results in a cross-sectional study of the prison environment and others obtained at our centre in self-administered treatment.


Regulation of IgE antibody production by serum molecules. III. Induction of suppressive activity by allogeneic lymphoid cell interactions and suppression of IgE synthesis by the allogeneic effect.
Antibody responses of the IgE class are, like other immunoglobulin classes, regulated by a finely-tuned network of complex cellular and molecular interactions (1). Previous studies conducted in our laboratory (2, 3) have provided new insights into the differences in control mechanisms that result in individuals manifesting either the high (allergic) or low (nonallergic) IgE responder phenotype. These experiments have shown that certain manipulations (i.e. low dose X-irradiation) convert normally low responder mice to high IgE responders, apparently by diminishing a suppressor T-cell mechanism which normally dampens, rather selectively, IgE antibody production in such individuals. Similar findings have been made by Watanabe et al. (4). Recently, we have been studying the types of manipulations that could reverse the high IgE responsive state back to a low one. These studies (2, 3, 5, 6) have demonstrated that the high IgE responses induced in low responder mice can be substantially diminished, and even abolished, by passively transfusing serum or ascetic fluid from donor mice previously inoculated with mycobacterial-containing complete Freund's adjuvant (CFA). Because the suppressive activity of CFA-immune serum or ascitic fluid is so highly selective for IgE antibody production, we have recently termed these serum substances suppressive factors of allergy (SFA) (2, 3). The present study was undertaken to determine whether alternative means, particularly those that avoid administration of CFA, could be devised for the induction of SFA. Herein, we report the effectiveness of allogeneic lymphoid cell interactions in inducing SFA, both in vivo and in vitro, as well as the potent suppressive effects of an in vivo allogeneic effect on irradiation enhanced IgE antibody production in low responder mice.


From the Cyclone Idai disaster to the COVID-19 pandemic: An account of inadvertent social capital enhancement in Eastern Chimanimani, Zimbabwe.
Zimbabwe suffered a devastating meteorological disaster when Cyclone Idai affected the southeast part of the country in March 2019. Barely a year after the cyclonic event, the coronavirus disease 2019 (COVID-19) pandemic emerged, leading to the declaration of a nationwide lockdown that paralysed socio-economic systems. This article examines how social capital was autonomously cultivated and eventually utilised by the Cyclone Idai disaster survivors in Eastern Chimanimani to face the fresh socio-economic challenges of the COVID-19 pandemic. In this article, a qualitative method embedded in a case study design was used. Data was collected using 30 purposively selected key respondents who interacted with victim communities from March to July 2020. A thematic content analysis approach was applied to obtain opinion patterns and subsequent inferences. The study results revealed a lack of immediate external disaster intervention during the Cyclone Idai disaster in Chimanimani. Accordingly, a strong sense of collective action developed between victim communities, thus enabling them to perform hasty operations meant to salvage lives and property. The enhanced social capital helped the Cyclone Idai victims to face the new COVID-19 lockdown challenges. This article recommends pro-active and well-coordinated government and private sector disaster response strategies supporting local area initiatives to minimise loss of lives and property during disaster situations.


Impact of covalent functionalization by diazonium chemistry on the electronic properties of graphene on SiC.
Plenty of strategies focused on covalent interaction have been developed to functionalize graphene's surface in order to employ it in a wide range of applications. Among them, the use of radical species including nitrene, carbene and aryl diazonium salts is regarded as a promising strategy to establish the covalent functionalization of graphene. In this work, we highlight the effect of diazonium chemistry on the electronic properties of graphene on SiC. On the basis of X-ray and synchrotron-based photoemission experiments, we were able to prove that 3,4,5-trimethoxybenzenediazonium (TMeOD) units, reduced and chemisorbed onto graphene using electrochemistry, preserve the electronic structure of the Dirac cone, through inducing a slightly additional n-type doping of graphene, as revealed by a downshift of the Dirac cone probed by angle-resolved photoemission experiments.


Multidrug Resistance-1 C3435T Polymorphism and Carbamazepine Plasma Level in Indonesian Temporal Lobe Epilepsy Patients.
Temporal lobe epilepsy (TLE) has the highest probability of becoming resistant. One of the causes was Polymorphism in multidrug resistant-1 (MDR1) C3435T. In Dr. Cipto Mangunkusumo Hospital, potential drug-resistant epilepsy prevalence was 84.51%; 66.6% of them used carbamazepine (CBZ) as antiseizure medication. This comparative cross-sectional study aimed to investigate MDR1 C3435T polymorphism and CBZ plasma level (plCBZ) in Indonesian TLE patients. TLE patient was selected consecutively; divided into drug-responsive (DRV) and drugresistant (DRE) groups. Healthy subjects were included as a control for the gene polymorphism comparison. MDR1 was identified using the restriction fragment length polymorphism PCR technique; C allele at 159 and 57bp while T allele at 216bp. High-performance liquid chromatography was used to determine plCBZ. There were 86 subjects; 61 in the study group and 25 controls. The genotype distribution between them was 0.58 vs 0.42, x2=0.54, p=0.000. In the study group, CBZ within therapeutic doses (dCBZ) had outreached the therapeutic plCBZ and found similar in all genotypes. DRE criteria were found in 37 subjects. Distribution of C and T in DRV was 0.63 vs 0.37, x2=10.4; and DRE 0.55 vs 0.45 x2=6.17 (p=0.019). In Tukey's multiple comparison post hoc test, CT in DRV had significantly lower dCBZ (330,36 ± 174,91 mg) and plCBZ (7.15 ± 2.64 mcg/mL) compared to all genotypes in DRE. Whereas mean dCBZ was around 800mg and plCBZ outreached the toxic level; TT was the highest. The genotype MDR1 distribution was similar in the normal population and DRE. Therapeutic plCBZ was achieved using the low dose. CT genotype responds to lower dCBZ, while TT genotype outreached the highest toxic plCBZ.


The Importance of Monitoring and Factors That May Influence Leg Length Difference in Developmental Dysplasia of the Hip.
In unilateral Developmental Dysplasia of the Hip (DDH), avascular necrosis (AVN), femoral or pelvic osteotomy, and residual dysplasia causing subluxation of the proximal femur may influence Leg Length Discrepancy (LLD). This can lead to gait compensation, pelvic obliquity, and spinal curvature. The aim of this study is to determine the prevalence of LLD, establish which limb segment contributes to the discrepancy, describe how AVN influences LLD, and ascertain variables that may influence the need for LLD corrective procedures. This study assessed long-leg radiographs at skeletal maturity. Radiographs were assessed for the articulo-trochanteric distance (ATD) and femoral and tibial length. AVN was classified according to Kalamchi-MacEwen. 109 patients were included. The affected/DDH leg was longer in 72/109 (66%) patients. The length difference was mainly in the subtrochanteric segment of the femur. AVN negatively influenced leg length. Older (≥three years) patients with multiple procedures were more likely to have AVN. LLD interventions were performed in 30 (27.5%) patients. AVN grade or type of DDH surgery did not influence the odds of needing a procedure to correct LLD. Procedures to correct LLD were performed irrespective of previous DDH surgery or AVN grades. In most patients, the affected/DDH leg was longer, mainly in the subtrochanteric segment of the femur, largely influenced by femoral osteotomy in patients with multiple operative procedures for DDH. We recommend careful monitoring of LLD in DDH.


Hypoxic loss of consciousness in air diving: two cases of mixtures made hypoxic by oxidation of the scuba diving cylinder.
Without an adequate supply of oxygen from the scuba apparatus, humans would not be able to dive. The air normally contained in a scuba tank is dry and free of toxic gases. The presence of liquid in the tank can cause corrosion and change the composition of the gas mixture. Various chemical reactions consume oxygen, making the mixture hypoxic. We report two cases of internal corrosion of a scuba cylinder rendering the respired gas profoundly hypoxic and causing immediate hypoxic loss of consciousness in divers.


Visual and auditory evoked responses in patients with Parkinson's disease.
Visual evoked responses were obtained in 47 Parkinsonian patients and 26 age-matched controls. The stimulation to binocular and uniocular latency of the major positive peak was longer in the Parkinsonian patients and its amplitude was smaller than in the control subjects. There was a large interocular difference suggesting that at least part of the delay occurs at prechiasmatic level. The latency and amplitude varied markedly following ingestion of levodopa as Sinemet. Auditory evoked potentials were obtained in 16 Parkinsonian patients and 11 age-matched controls. The latency of the NV wave was prolonged in the former although the amplitude was the same, suggesting that the abnormality may be a widespread one.


Selenium and psoriasis.
Psoriasis is a chronic, immune-mediated skin disease characterized by production of reactive oxygen species due to the activation of tumor necrosis factor alpha (TNF-α), which is thought to be an important factor in inducing and maintaining psoriatic lesions. As an external factor, ultraviolet B (UVB) radiation stimulates TNF-α production and secretion by human keratinocytes in vitro and can also reach the upper dermis and suppress endothelial cells in vitro. The selenium level in psoriatic patients has been found to be lower than expected, but studies on its role in the pathogenesis of the disease are scarce. Selenium can influence immune response by changing the expression of cytokines and their receptors or by making immune cells more resistant to oxidative stress. It was reported that selenium supplementation had inhibitory effects on TNF-α levels in patients with psoriasis, but the details are not completely elucidated. Selenium compounds are also known to prevent the in vitro release of UVB-induced proinflammatory cytokines by inhibition of mRNA in human keratinocytes. In the present review, the protective role of selenium in oxidative stress, lesions, and immune system regulation in patients with psoriasis is summarized.


Determination of trace elements in goat and ovine milk from Calabria (Italy) by ICP-AES.
There are many sources of contamination to which milk could be exposed: grazing animals can ingest contaminants present in nature, such as lead in soil, or that have been deposited on grass, resulting from industrial emissions. Another possible route of contamination is represented by feed for animals, which may contain heavy and essential metals. The potential of high-resolution inductively coupled plasma spectrometry was evaluated to quantify reliably various toxic and essential elements (Fe, Zn, Pb, Cr, Ni, Cu, As, Se, Cd) in 47 samples of goat and ovine milk from various farms in Calabria (southern Italy). The results showed that concentrations of cadmium were below the limit of detection. Lead levels were below the maximum limits as set by the EC in almost all samples tested. The highest values were those of Zn followed by Fe, Cu and Se.


No evidence of overweight in long-term survivors of childhood cancer after glucocorticoid treatment.
Glucocorticoids can lead to weight gain during cancer treatment, but to the authors' knowledge, little is known regarding their long-term effects in childhood cancer survivors (CCS). As part of the Swiss Childhood Cancer Survivor Study, the authors sent a questionnaire to CCS aged <21 years at diagnosis who were residing in Switzerland, had survived ≥5 years, and were aged 15 to 45 years at the time of the survey. Cumulative doses of glucocorticoids were assessed from medical records and study protocols and body mass index was calculated from self-reported height and weight at the time of the survey. The authors compared the prevalence of overweight between CCS, their siblings, and the general population (Swiss Health Survey [SHS]) and investigated the association between overweight and treatment-related risk factors using multivariable logistic regression. The study included 1936 CCS, 546 siblings, and 9591 SHS participants. The median age of the CCS at the time of the survey was 24 years (interquartile range, 20-31 years) and the median time since diagnosis was 17 years (interquartile range, 12-22 years). At the time of the survey, approximately 26% of CCS were overweight, a percentage that was comparable to that among siblings (24%) and the SHS participants (25%). The prevalence of overweight was 24% in CCS treated with glucocorticoids only (686 CCS), 37% in those treated with cranial radiotherapy (CRT) (127 CCS), and 49% in those who received treatment with both glucocorticoids and CRT (101 CCS) (P < .001). The authors found no evidence of a dose-response relationship between cumulative glucocorticoid doses and overweight and no evidence that CRT modified the effect of the cumulative glucocorticoid dose on overweight. The results of the current study suggest that glucocorticoids used for the treatment of childhood cancer are not associated with long-term risk of overweight.


Cellular uptake of nanoparticles as determined by particle properties, experimental conditions, and cell type.
The increased application of nanoparticles (NPs) is increasing the risk of their release into the environment. Although many toxicity studies have been conducted, the environmental risk is difficult to estimate, because uptake mechanisms are often not determined in toxicity studies. In the present study, the authors review dominant uptake mechanisms of NPs in cells, as well as the effect of NP properties, experimental conditions, and cell type on NP uptake. Knowledge of NP uptake is crucial for risk assessment and is essential to predict the behavior of NPs based on their physical-chemical properties. Important uptake mechanisms for eukaryotic cells are macropinocytosis, receptor-mediated endocytosis, and phagocytosis in specialized mammalian cells. The studies reviewed demonstrate that uptake into nonphagocytic cells depends strongly on NP size, with an uptake optimum at an NP diameter of approximately 50 nm. Increasing surface charges, either positive or negative, have been shown to increase particle uptake in comparison with uncharged NPs. Another important factor is the degree of (homo-) aggregation. Results regarding shape have been ambiguous. Difficulties in the production of NPs, with 1 property changed at a time, call for a full characterization of NP properties. Only then will it be possible to draw conclusions as to which property affected the uptake.


Development of peltate glandular trichomes of peppermint.
Cryofixation and conventional chemical fixation methods were employed to examine the ultrastructure of developing peltate glandular trichomes of peppermint (Mentha x piperita). Our results are discussed in relation to monoterpene production and the mechanism of essential oil secretion. Peltate glands arise as epidermal protuberances (initials) that divide asymmetrically to produce a vacuolate basal cell, a stalk cell, and a cytoplasmically dense apical cell. Further divisions of the apical cell produce a peltate trichome with one basal cell, one stalk cell, and eight glandular (secretory) disc cells. Presecretory gland cells resemble meristematic cells because they contain proplastids, small vacuoles, and large nuclei. The secretory phase coincides with the separation and filling of the sub-cuticular oil storage space, the maturation of glandular disc cell leucoplasts in which monoterpene biosynthesis is known to be initiated, and the formation of extensive smooth endoplasmic reticulum at which hydroxylation steps of the monoterpene biosynthetic pathway occur. The smooth endoplasmic reticulum of the secretory cells appears to form associations with both the leucoplasts and the plasma membrane bordering the sub-cuticular oil storage cavity, often contains densely staining material, and may be involved with the transport of the monoterpene-rich secretion product. Associated changes in the ultrastructure of the secretory stage stalk cell are also described, as is the ultrastructure of the fragile post-secretory gland for which cryofixation methods are particularly well suited for the preservation of organizational integrity.