Does the COVID-19 Pandemic Change Consumers' Food Consumption and Willingness-to-Pay? The Case of China.
Since COVID-19 was first detected in China in 2019, governments around the world have imposed strict measures to curb the spread of the coronavirus, which substantially impacted people's life. Consumers' food consumption behavior has also changed accordingly with reduced grocery shopping frequency, replaced in-person grocery shopping with online shopping, and increased valuation on food. In this paper, we aim to investigate the change in Chinese consumers' food consumption and their willingness to pay (WTP) for vegetables and meat, using a dataset with 1206 online samples collected between February and March 2020. Consumers' WTP for vegetables and meat is estimated using a double-bounded dichotomous contingent valuation design, and factors affecting their WTPs are also investigated. Results show that consumers have a higher WTP for these food products during the pandemic, and their WTP is positively affected by their anticipated duration of the COVID-19, their online shopping shares, their direct exposure to infected patients, their gender, and their income. These results imply that the food industry shall try to develop online market channels as consumers are willing to share the costs, while lower-income consumers may not be able to meet their food needs with prices increased beyond their WTP and thus may call for the government's support.


Vibration displacement immunization model for measuring the free spectral range by means of a laser self-mixing velocimeter.
In this paper, a vibration-displacement immunization model is proposed to measure the free spectral range of a resonant cavity by using a laser self-mixing velocimeter. The validity of this method is demonstrated by the experimental results, which can effectively get rid of low measurement accuracy related to the self-mixing vibration system due to the vibratory displacement. According to the periodic waveform separation characteristic of the self-mixing velocity signal, the free spectral range of a multilongitudinal mode diode laser is calculated to be 88.24 GHz. Moreover, the influences of different target velocities and signal sampling frequencies on the free spectral range have been analyzed in detail from the theoretical analysis. In the case of high signal sampling rate and low velocity, from which the undistorted velocity signal waveform at the integral order external cavity mode keeps stable, it is possible to obtain relatively accurate measured results.


[Characteristics of tuberculosis epidemiology in Moscow and improvement measures].
The trends in tuberculosis morbidity for the recent 30 years and factors that caused tuberculosis incidence to rise by 13.5% in 1992 are analyzed. Infiltrative-disseminated, disseminated and fibrous-cavernous tuberculosis were diagnosed in 58.7%, 11.7% and 1.8% of cases, respectively. Destructive lesion was found in 50% of the patients. Tuberculosis mortality reached in 1992 4.6 per 100,000. Measures to control tuberculosis spread in Moscow are suggested.


The most effective strategy for recruiting a pregnancy cohort: a tale of two cities.
Pregnant women were recruited into the Alberta Pregnancy Outcomes and Nutrition (APrON) study in two cities in Alberta, Calgary and Edmonton. In Calgary, a larger proportion of women obtain obstetrical care from family physicians than from obstetricians; otherwise the cities have similar characteristics. Despite similarities of the cities, the recruitment success was very different. The purpose of this paper is to describe recruitment strategies, determine which were most successful and discuss reasons for the different success rates between the two cities. Recruitment methods in both cities involved approaching pregnant women (< 27 weeks gestation) through the waiting rooms of physician offices, distributing posters and pamphlets, word of mouth, media, and the Internet. Between May 2009 and November 2010, 1,200 participants were recruited, 86% (1,028/1,200) from Calgary and 14% (172/1,200) from Edmonton, two cities with similar demographics. The most effective strategy overall involved face-to-face recruitment through clinics in physician and ultrasound offices with access to a large volume of women in early pregnancy. This method was most economical when clinic staff received an honorarium to discuss the study with patients and forward contact information to the research team. Recruiting a pregnancy cohort face-to-face through physician offices was the most effective method in both cities and a new critically important finding is that employing this method is only feasible in large volume maternity clinics. The proportion of family physicians providing antenatal and post-natal care may impact recruitment success and should be studied further.


Capsaicin activates heat loss and heat production simultaneously and independently in rats.
Subcutaneous administration of capsaicin (5 mg/kg) immediately increased the temperature of the tail skin (Tsk) for 2 h in urethan-anesthetized rats, suggesting an increase in heat loss. O2 consumption, an index of heat production, also immediately increased after the capsaicin injection, and this increase lasted for >10 h. Colonic temperature (Tco) decreased within 1 h after the injection, and this decrease was followed by a long-lasting hyperthermic period. Adrenal demedullation largely attenuated the capsaicin-induced increase in O2 consumption, and sympathetic denervation of the interscapular brown adipose tissue partly attenuated the increase in O2 consumption. However, capsaicin-induced heat loss was normal in these rats. In rats with cutaneous vasodilation maximized by warming and administration of hexamethonium, capsaicin did not further increase Tsk but normally induced heat production, and Tco gradually rose without a hypothermic period. Thus capsaicin simultaneously increased heat loss and heat production, and inhibition of one response did not affect the other. These findings suggest that capsaicin simultaneously activates independent networks for heat loss and heat production.


Individualized antibiotic therapy in patients with ventilator-associated pneumonia.
The optimal duration of the treatment of ventilator-associated pneumonia (VAP) is still the subject of debate. While 1 week treatment has been reported as possibly sufficient, patients generally receive antibiotic therapy for 10 to 14 days. The purpose of our study was to investigate whether length of treatment in patients with VAP can be reduced with an individualized therapeutic strategy. The study was performed prospectively with patients diagnosed with VAP in our hospital's intensive care units between 1 January and 31 December 2015. Duration of antibiotic therapy was determined with 5 day clinical evaluation according to previously established criteria. Patients were divided into two groups depending on length of treatment, short (7-10 days) and long treatment (>10 days). Nineteen patients received 7 to 10 day antibiotic therapy, and 30 received >10 day antibiotic therapy. Demographic and clinical characteristics, Glasgow Coma Scale score, CPIS and the PaO2/FiO2 ratio at the time of diagnosis of VAP were statistically similar between the two groups (P>0.05). A second VAP attack occurred post-treatment in three patients receiving short-term treatment and in four receiving long-term treatment (P=0.561). The numbers of antibiotic-free days were 15.6±6.2 in the short-term treatment group and 8.3±7.5 in the long-term group (P<0.0001). One of the patients receiving short-term treatment died within 28 days after treatment, and four of the patients receiving long-term treatment (P=0.348) did so. The most commonly observed micro-organisms in both groups were Acinetobacterbaumannii and Pseudomonasaeruginosa. Short-term treatment can be administered in cases with early clinical and laboratory response started on VAP treatment by considering individual characteristics and monitoring fever, CPIS, the PaO2/FiO2 ratio, C-reactive protein and procalcitonin values.


Prevention of Prescription Opioid Misuse and Projected Overdose Deaths in the United States.
Deaths due to opioid overdose have tripled in the last decade. Efforts to curb this trend have focused on restricting the prescription opioid supply; however, the near-term effects of such efforts are unknown. To project effects of interventions to lower prescription opioid misuse on opioid overdose deaths from 2016 to 2025. This system dynamics (mathematical) model of the US opioid epidemic projected outcomes of simulated individuals who engage in nonmedical prescription or illicit opioid use from 2016 to 2025. The analysis was performed in 2018 by retrospectively calibrating the model from 2002 to 2015 data from the National Survey on Drug Use and Health and the Centers for Disease Control and Prevention. Comparison of interventions that would lower the incidence of prescription opioid misuse from 2016 to 2025 based on historical trends (a 7.5% reduction per year) and 50% faster than historical trends (an 11.3% reduction per year), vs a circumstance in which the incidence of misuse remained constant after 2015. Opioid overdose deaths from prescription and illicit opioids from 2016 to 2025 under each intervention. Under the status quo, the annual number of opioid overdose deaths is projected to increase from 33 100 in 2015 to 81 700 (95% uncertainty interval [UI], 63 600-101 700) in 2025 (a 147% increase from 2015). From 2016 to 2025, 700 400 (95% UI, 590 200-817 100) individuals in the United States are projected to die from opioid overdose, with 80% of the deaths attributable to illicit opioids. The number of individuals using illicit opioids is projected to increase by 61%-from 0.93 million (95% UI, 0.83-1.03 million) in 2015 to 1.50 million (95% UI, 0.98-2.22 million) by 2025. Across all interventions tested, further lowering the incidence of prescription opioid misuse from 2015 levels is projected to decrease overdose deaths by only 3.0% to 5.3%. This study's findings suggest that interventions targeting prescription opioid misuse such as prescription monitoring programs may have a modest effect, at best, on the number of opioid overdose deaths in the near future. Additional policy interventions are urgently needed to change the course of the epidemic.


Update on acute flaccid myelitis: recognition, reporting, aetiology and outcomes.
Acute flaccid myelitis, defined by acute flaccid limb weakness in the setting of grey matter lesions of the spinal cord, became increasingly recognised in 2014 following outbreaks in Colorado and California, temporally associated with an outbreak of enterovirus D68 respiratory disease. Since then, there have been biennial increases in late summer/early fall. A viral infectious aetiology, most likely enteroviral, is strongly suspected, but a definitive connection has yet to be established. Patients typically present with asymmetric weakness, maximal proximally, in the setting of a febrile illness. MRI demonstrates T2/FLAIR abnormalities in the central grey matter of the spinal cord, and cerebrospinal fluid typically shows a lymphocytic pleocytosis with variable elevation in protein. The weakness may be progressive over several days and involve respiratory muscles, making early recognition and close monitoring essential. Other complications in the acute period may include autonomic instability and bowel/bladder involvement. There is no clear recommended treatment at this time, although intravenous immunoglobulin, steroids and plasma exchange have been used. Intensive therapies and rehab services have shown benefit in maximising function, and surgical interventions may be considered in cases without optimal response to therapies. Close attention should also be paid to psychosocial factors. Prognosis is generally guarded, and additional factors that predict final outcome, including host factors and treatment effects, have yet to be elucidated. Multicentre collaborative efforts will be required to provide answers about this rare but serious disorder.


Cytokines in candidiasis and aspergillosis.
Both innate and T helper (Th) immunity play a central role in fungal infections. A bi-directional influence exists between the two compartments of the immune system, mainly occurring through cytokine production. On the one hand, protective Th1 or nonprotective Th2 cells mediate resistance or susceptibility to disseminated and localized fungal infections by secreting cytokines with activating or deactivating signals for effector phagocytic cells. On the other hand, cells of the innate immune system regulate the development of antifungal T helper responses by producing directive cytokines, such as interleukin (IL)-12 and IL-10. In experimental models of Candida albicans and Aspergillus fumigatus infections, the administration or neutralization of selective cytokines and the use of cytokine-deficient mice have revealed the existence of a hierarchical pattern of cytokine mediated regulation of antifungal Th cell development and effector function. A finely regulated balance of directive cytokines, rather than the relative absence of opposing cytokines, appears to be required for optimal development and maintenance of protective Th1 reactivity to fungi. Thus, it is conceivable that some cytokines may have beneficial or deleterious effects on infection, depending on the dose and timing of endogenous production or exogenous administration. A better understanding of the different, sometimes unexpected, roles of cytokines is required for their use in prophylaxis and therapy of fungal infections, either alone or in combination with antifungal agents.


Functional traits explain ecosystem function through opposing mechanisms.
The ability to explain why multispecies assemblages produce greater biomass compared to monocultures, has been a central goal in the quest to understand biodiversity effects on ecosystem function. Species contributions to ecosystem function can be driven by two processes: niche complementarity and a selection effect that is influenced by fitness (competitive) differences, and both can be approximated with measures of species' traits. It has been hypothesised that fitness differences are associated with few, singular traits while complementarity requires multidimensional trait measures. Here, using experimental data from plant assemblages, I show that the selection effect was strongest when trait dissimilarity was low, while complementarity was greatest with high trait dissimilarity. Selection effects were best explained by a single trait, plant height. Complementarity was correlated with dissimilarity across multiple traits, representing above and below ground processes. By identifying the relevant traits linked to ecosystem function, we obtain the ability to predict combinations of species that will maximise ecosystem function.


Cardiac Stroke Volume Index Is Associated With Early Neurological Improvement in Acute Ischemic Stroke Patients.
Early neurological improvement as assessed with the NIH stroke scale (NIHSS) at 24 h has been associated with improved long-term functional outcomes following acute ischemic stroke (AIS). Cardiac dysfunction is often present in AIS, but its association with outcomes is incompletely defined. We performed a pilot study to evaluate the association between non-invasively measured cardiac parameters and 24-h neurological improvement in prospectively enrolled patients with suspected AIS who presented within 12 h of symptom-onset and had an initial systolic blood pressure>140 mm Hg. Patients receiving thrombolytic therapy or mechanical thrombectomy were excluded. Non-invasive pulse contour analysis was used to measure mean arterial blood pressure (MAP), cardiac stroke volume index (cSVI), cardiac output (CO) and cardiac index (CI). Transcranial Doppler recorded mean middle cerebral artery flow velocity (MFV). We defined a decrease of 4 NIHSS points or NIHSS ≤ 1 at 24-h as neurological improvement. Of 75 suspected, 38 had confirmed AIS and did not receive reperfusion therapy. Of these, 7/38 (18.4%) had neurological improvement over 24 h. MAP was greater in those without improvement (108, IQR 96-123 mm Hg) vs. those with (89, IQR 73-104 mm Hg). cSVI, CO, and MFV were similar between those without and with improvement: 37.4 (IQR 30.9-47.7) vs. 44.7 (IQR 42.3-55.3) ml/m2; 5.2 (IQR 4.2-6.6) vs. 5.3 (IQR 4.7-6.7) mL/min; and 39.9 (IQR 32.1-45.7) vs. 34.4 (IQR 27.1-49.2) cm/s, respectively. Multivariate analysis found MAP and cSVI as predictors for improvement (OR 0.93, 95%CI 0.85-0.98 and 1.14, 95%CI 1.03-1.31). In this pilot study, cSVI and MAP were associated with 24-h neurological improvement in AIS.


Adaptive coded-aperture imaging with subpixel superresolution.
We describe an adaptive coded-aperture imager operating in the midwave IR. This consists of a coded-aperture mask, a set of optics, and a 4k×4k focal plane array (FPA). This system can produce images with a resolution better than the detector pixel limit by combining multiple frames of data recorded with different coding. This superresolution capability has been demonstrated both in the laboratory and with targets placed outside, the highest resolution being one-half of the FPA pixel pitch.


Gating kinetics of Shaker K+ channels are differentially modified by general anesthetics.
The ShakerB K+ channel was used as a model voltage-gated channel to probe the interaction of volatile general anesthetics with gating mechanisms. The effects of three anesthetics, chloroform (CHCl3), isoflurane, and halothane, were studied using recombinant native and mutant Shaker channels expressed in Xenopus oocytes. Gating currents and macroscopic ionic currents were recorded with the cut-open oocyte voltage-clamp technique. The effects of CHCl3 and isoflurane on gating kinetics of noninactivating mutants were opposite, whereas halothane had no effect. The effects on ionic currents were also agent dependent: CHCl3 and halothane produced a reduction of the macroscopic conductance, whereas isoflurane increased it. The results indicate that the gating machinery of the channel is mostly insensitive to the anesthetics during activation until near the open state. The effects on the conductance are mainly due to changes in the transitions in and out of the open state. The data give support to direct protein-anesthetic interactions. The magnitude and nature of the effects invite reconsideration of Shaker-like K+ channels as important sites of action of general anesthetics.


Testing different thresholds for risky episodic drinking--what's so special about five drinks?
Studies of episodic drinking typically use a measure based on the frequency of drinking five or more standard drinks (a definition which itself varies based on the standard units being used). While this threshold clearly defines drinking behaviour with a range of risks and negative consequences, there has been limited research outside of US college-based studies to determine the appropriateness of this definition. This study examines fifteen different risky-drinking thresholds to assess which definitions of risky drinking best predict negative outcomes. This paper presents an analysis of a national survey sample of 19,757 drinkers. The appropriateness of each threshold is assessed using basic risk-curves, specificity and sensitivity analyses and the performance of each threshold definition in multivariate logistic regression models. Risky drinking was defined in fifteen ways (based on frequency and volume) and tested against a series of self-reported negative outcomes and risky behaviours. The study finds that the most appropriate risky drinking threshold for these data varies based on the mode of analysis and on the type of outcome being considered. Across all approaches used, risky drinking thresholds of seven or fewer drinks performed better than higher thresholds. While individual level risks peak at higher levels of consumption, these findings support the continuing use of relatively low thresholds for defining risky-drinking, as risk across the total population is highest at these levels.


Part and whole practice: chunking and online control in the acquisition of a serial motor task.
A four-component aiming movement was used to examine the relative effectiveness of part and whole practice. Following a pretest, participants were assigned to one of three practice groups. Participants in a "Whole" group practiced the four components together as a unit. A "No Overlap" group practiced the first two and last two components of the task, alternating every fifth trial. An "Overlap" group practiced the transition between the second and third components on every trial by alternating practice of the first three and last three components every five trials. Participants in all groups improved significantly from pretest to immediate posttest and maintained their performance over a 24-hr delay. Contrary to the "chunking hypothesis," participants in the No Overlap group improved as much as those in the other two groups. Kinematic data indicated that participants in all three groups learned to use response-produced feedback earlier in the individual movement trajectories. Moreover, participants appeared to acquire a general ability to make transitions between movement components rather than specific transitions. The results suggest that segmented or segmented "overlap" practice regimes may benefit learning movement sequences of short duration.


A miniature transducer for recording intestinal motility in unrestrained chronic rats.
An extraluminal strain gage force transducer has been developed for recording gastrointestinal motility in small animals such as rats. Two commercial strain gages are bonded and wires attached to form half a Wheatstone bridge. The device is placed between silicone sheeting and prepared for implantation. As many as six implanted transducers can record simultaneously contractions and tone variations of circular or longitudinal gastrointestinal muscles. The transducers have been implanted in more than 20 rats, with some units lasting up to 4 mo. Furthermore, good relationships exist between intraluminal pressure waves registered by a small intraluminal balloon and gut contractions registered by the transducer. The transducers are a useful and accurate tool for rodent gut motility studies.


Retrograde amnesia produced by several treatments: evidence for a common neurobiological mechanism.
This experiment examined the effects on memory of various amnestic treatments in animals earlier treated with the alpha-adrenergic antagonist phenoxybenzamine (PBZ). Thirty minutes before being trained in a one-trial inhibitory (passive) avoidance task, animals received an injection of PBZ or saline. Immediately after training, each animal received one of the following amnestic treatments: stimulation of the frontal cortex or amygdala, pentylenetetrazol, diethyldithiocarbamate, or cycloheximide. In control animals, each treatment produced retrograde amnesia. However, PBZ-treated animals did not develop amnesia. These findings suggest that there may be a common neurobiological mechanism underlying the amnesias produced by many treatments.


In vivo genetic manipulation of cortical progenitors in gyrencephalic carnivores using in utero electroporation.
Brain structures such as the outer subventricular zone (OSVZ) and the inner fiber layer (IFL) in the developing cerebral cortex are especially prominent in higher mammals. However, the molecular mechanisms underlying the formation of the OSVZ are still largely unknown, mainly because genetic manipulations that can be applied to the OSVZ in higher mammals had been poorly available. Here we developed and validated a rapid and efficient genetic manipulation technique for germinal zones including the OSVZ using in utero electroporation in developing gyrencephalic carnivore ferrets. We also determined the optimal conditions for using in utero electroporation to express transgenes in germinal zones. Using our electroporation procedure, the morphology of GFP-positive cells in the OSVZ was clearly visible even without immunostaining, and multiple genes were efficiently co-expressed in the same cells. Furthermore, we uncovered that fibers, which seemed to correspond to those in the IFL of monkeys, also existed in ferrets, and were derived from newly generated cortical neurons. Our technique promises to be a powerful tool for investigating the fundamental mechanisms underlying the formation and abnormalities of the cerebral cortex in higher mammals.


The technology of accelerometry-based activity monitors: current and future.
This paper reviews accelerometry-based activity monitors, including single-site first-generation devices, emerging technologies, and analytical approaches to predict energy expenditure, with suggestions for further research and development. The physics and measurement principles of the accelerometer are described, including the sensor properties, data collections, filtering, and integration analyses. The paper also compares these properties in several commonly used single-site accelerometers. The emerging accelerometry technologies introduced include the multisensor arrays and the combination of accelerometers with physiological sensors. The outputs of accelerometers are compared with criterion measures of energy expenditure (indirect calorimeters and double-labeled water) to develop mathematical models (linear, nonlinear, and variability approaches). The technologies of the sensor and data processing directly influence the results of the outcome measurement (activity counts and energy expenditure predictions). Multisite assessment and combining accelerometers with physiological measures may offer additional advantages. Nonlinear approaches to predict energy expenditure using accelerometer outputs from multiple sites and orientation can enhance accuracy. The development of portable accelerometers has made objective assessments of physical activity possible. Future technological improvements will include examining raw acceleration signals and developing advanced models for accurate energy expenditure predictions.


Quality Improvement Approach to Reducing Admission Hypothermia Among Preterm and Term Infants.
Newborns, particularly premature newborns, are susceptible to hypothermia when transitioning from birth to admission to the NICU, potentially leading to increased mortality and morbidity. Despite attention to this issue, our rate of admission hypothermia was 39.8%. We aimed to reduce the rate of admission hypothermia for all inborn infants admitted to our institution to <10%. We undertook a quality improvement effort that spanned from 2013 through 2019 in our level IV NICU. Current state analysis involved investigating patient risk factors for hypothermia and staff understanding of hypothermia prevention. Improvement cycles included auditing processes, an in-hospital relocation of our NICU, expanded use of chemical heat mattresses and polyethylene bags, and staff education. Improvement was evaluated by using Shewhart control charts. We demonstrated a reduction in admission hypothermia from 39.8% to 9.9%, which was temporally related to educational efforts and expanded use of chemical heat mattresses and polyethylene bags. There was not an increase in admission hyperthermia over this time period. We found that our group at highest risk of admission hypothermia was not our most premature cohort but those infants born between 33 and 36 6/7 weeks' gestation and those infants prenatally diagnosed with congenital anomalies. Expanded use of polyethylene bags and chemical heat mattresses can improve thermoregulation particularly when combined with staff education. Although premature infants have been the focus of many hypothermia prevention efforts, our data suggest that older infants, and those infants born with congenital anomalies, require additional attention.


High Rate of Infection by Only Oncogenic Human Papillomavirus in Amerindians.
Human papillomavirus (HPV), an etiological agent of cervical cancer (CC), has infected humans since ancient times. Amerindians are the furthest migrants out of Africa, and they reached the Americas more than 14,000 years ago. Some groups still remain isolated, and some migrate to towns, forming a gradient spanning urbanization. We hypothesized that, by virtue of their history, lifestyle, and isolation from the global society, remote Amerindian women have lower HPV diversity than do urban women (Amerindian or mestizo). Here we determined the diversity of the 25 most relevant cervical HPV types in 82 Amerindians spanning urbanization (low, medium, and high, consistent with the exposure to urban lifestyles of the town of Puerto Ayacucho in the Venezuelan Amazonas State), and in 29 urban mestizos from the town. Cervical, anal, oral, and introitus samples were taken, and HPVs were typed using reverse DNA hybridization. A total of 23 HPV types were detected, including 11 oncogenic or high-risk types, most associated with CC. Cervical HPV prevalence was 75%, with no differences by group, but Amerindians from low and medium urbanization level had significantly lower HPV diversity than mestizos did. In Amerindians, but not in mestizos, infections by only high-risk HPVs were higher than coinfections or by exclusively low-risk HPVs. Cervical abnormalities only were observed in Amerindians (9/82), consistent with their high HPV infection. The lower cervical HPV diversity in more isolated Amerindians is consistent with their lower exposure to the global pool, and transculturation to urban lifestyles could have implications on HPV ecology, infection, and virulence.IMPORTANCE The role of HPV type distribution on the disparity of cervical cancer (CC) incidence between human populations remains unknown. The incidence of CC in the Amazonas State of Venezuela is higher than the national average. In this study, we determined the diversity of known HPV types (the viral agent of CC) in Amerindian and mestizo women living in the Venezuelan Amazonas State. Understanding the ecological diversity of HPV in populations undergoing lifestyle transformations has important implication on public health measures for CC prevention.


Teratoma-associated anti-NMDAR encephalitis: Two cases report and literature review.
This study aimed to discuss the pathogenesis, clinical manifestation, diagnosis, and treatment of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. The diagnosis and treatment of 2 cases with teratoma-associated anti-NMDAR encephalitis were summarized and the clinical data of patients reported by domestic and international studies were reviewed in this study. The 2 cases were both adolescent females who showed mental abnormalities as their main clinical manifestation. The patients were positive for anti-NMDAR antibody in their serum and cerebrospinal fluid, and gynecologic ultrasound detected ovarian teratoma. After diagnosis, the patients underwent teratoma resection, followed by pulse therapy of hormones and gamma globulin. Chemotherapy was performed to prevent tumor recurrence, and patients were in a stable condition. Teratoma-associated anti-NMDAR encephalitis is commonly seen in young women. The clinical manifestation of this disease is nonspecific, and the patients mainly have fever, psychosis, and seizure. Tumor resection and immune therapy are effective treatment strategies, and standardized chemotherapy should also be performed to prevent recurrence.


The Pediatric AIDS Corps: responding to the African HIV/AIDS health professional resource crisis.
Health professional capacity for delivery of HIV/AIDS care and treatment is severely constrained across sub-Saharan Africa. African health professional expertise in pediatrics is in particularly short supply. Here we describe a Pediatric AIDS Corps program that was designed to place pediatricians and other physicians in Africa on a long-term basis to expand existing health professional capacity for pediatric and family HIV/AIDS care and treatment. In the first 2 years of this program, 76 physicians were placed in 5 African countries that have been hit hard by HIV/AIDS. Enrollment of HIV-infected children in care more than quadrupled over a 24-month period, to 26 590. We believe that this pilot program can serve as a model for larger-scale efforts to immediately expand access for African children and families to life-saving HIV/AIDS care and treatment.


Review of concrete biodeterioration in relation to nuclear waste.
Storage of radioactive waste in concrete structures is a means of containing wastes and related radionuclides generated from nuclear operations in many countries. Previous efforts related to microbial impacts on concrete structures that are used to contain radioactive waste showed that microbial activity can play a significant role in the process of concrete degradation and ultimately structural deterioration. This literature review examines the research in this field and is focused on specific parameters that are applicable to modeling and prediction of the fate of concrete structures used to store or dispose of radioactive waste. Rates of concrete biodegradation vary with the environmental conditions, illustrating a need to understand the bioavailability of key compounds involved in microbial activity. Specific parameters require pH and osmotic pressure to be within a certain range to allow for microbial growth as well as the availability and abundance of energy sources such as components involved in sulfur, iron and nitrogen oxidation. Carbon flow and availability are also factors to consider in predicting concrete biodegradation. The microbial contribution to degradation of the concrete structures containing radioactive waste is a constant possibility. The rate and degree of concrete biodegradation is dependent on numerous physical, chemical and biological parameters. Parameters to focus on for modeling activities and possible options for mitigation that would minimize concrete biodegradation are discussed and include key conditions that drive microbial activity on concrete surfaces.


Erving Goffman's asylums and institutional culture in the mid-twentieth-century United States.
Sociologist Erving Goffman based his seminal work Asylums (1961) on a year of field research at St. Elizabeths Hospital in Washington, DC. Goffman described the mental hospital as a "total institution," in which regimentation dominated every aspect of daily life and patients were denied even the most basic means of self-expression; rather than promote recovery, such conditions produced the sorts of disordered behavior for which men and women were ostensibly admitted. A closer look at the changes transforming St. Elizabeths around the time of Goffman's research reveals a far richer portrait of institutional culture. Group therapy, psychodrama, art and dance therapy, patient newspapers, and patient self-government-each of which debuted at the hospital in the 1940s and 1950s-provided novel opportunities for men and women to make themselves heard and to take their fate into their own hands. While these initiatives did not reach all of the patients at St. Elizabeths, surviving documentation suggests that those who participated found their involvement rewarding and empowering. Goffman explicitly set out to describe "the social world of the hospital inmate." His failure to appreciate fully the capacities of his subjects, however, appears to have led him to underestimate the importance of these developments.


New directions in prostaglandin research and their possible implications for immunologic and nonimmunologic inflammation.
New information on prostaglandins and related structures derived from arachidonic acid is accumulating rapidly. Of particular interest is evidence for the existence of labile, highly biologically active, nonprostanoate derivatives. A role for the classic prostaglandins in immunologic inflammation is already strongly suspected, and it seems likely that the newly recognized arachidonic acid metabolites may prove to be even more important.


Phytochemical, antioxidant and antimicrobial properties of Litsea angulata extracts.
Background:Litsea angulata is a plant species belonging to Lauraceae family that is distributed throughout Indonesia, Malaysia, and New Guinea. The seeds have been traditionally used by local people in Kalimantan, Indonesia for the treatment of boils; however, there is no information about the potency of its branch, bark and leaves yet. This study aimed to determine the antioxidant, antimicrobial activity as well as the phytochemical constituent of Litsea angulata branch, bark, and leaves. Methods: Extraction was performed by successive maceration method using n-hexane, ethyl acetate, and ethanol solvent. Antioxidant activity was evaluated by DPPH radical scavenging assay. The antimicrobial activity using the 96 well-plate microdilution broth method against Staphylococcus aureus and Streptococcus mutans. Results: Based on the phytochemical analysis, it showed that extract of L. angulata contains alkaloids, flavonoids, tannins, terpenoids, and coumarin. The results showed that all extracts of plant samples displayed the ability to inhibit DPPH free radical formation and all tested microorganisms. Conclusions:L. angulata contains secondary metabolites such as alkaloids, flavonoids, tannins, terpenoids, carotenoids, and coumarin. The antioxidant activity on different plant extracts was a range as very strong to weak capacity. All extracts in this study could inhibit the growth of S. aureus and S. mutans.


Recent Advances in the Development of Antidepressants Targeting the Purinergic P2X7 Receptor.
The purinergic P2X7 receptor (P2X7R) is an adenosine triphosphate (ATP)- gated cation channel protein. Although extracellular ATP (eATP) is maintained at the nanomolar concentration range under normal conditions, it is elevated to micromolar levels in response to cell stress or damage, resulting in activation of P2X7R in the brain. The binding of eATP to P2X7R in glial cells in the brain activates the NLRP3 inflammasome and releases pro-inflammatory cytokines, such as IL-1β, IL-6, IL-18, and TNFα. Depression has been demonstrated to be strongly associated with neuroinflammation activated by P2X7R. Therefore, P2X7R is an attractive therapeutic target for depression. Multinational pharmaceutical companies, including AstraZeneca, GlaxoSmithKline, Janssen, Lundbeck, and Pfizer, have developed CNS-penetrating P2RX7 antagonists. Several of these have been evaluated in clinical trials. This review summarizes the recent development of P2X7R antagonists as novel antidepressant agents in terms of structural optimization, as well as in vitro/in vivo evaluation and physicochemical properties of representative compounds.


Low-Molecular-Weight Fish Collagen Peptide (Valine-Glycine-Proline-Hydroxyproline-Glycine-Proline-Alanine-Glycine) Prevents Osteoarthritis Symptoms in Chondrocytes and Monoiodoacetate-Injected Rats.
The objective of this study was to investigate the effect of low-molecular-weight fish collagen (valine-glycine-proline-hydroxyproline-glycine-proline-alanine-glycine; LMWCP) on H2O2- or LPS-treated primary chondrocytes and monoiodoacetate (MIA)-induced osteoarthritis rat models. Our findings indicated that LMWCP treatment exhibited protective effects by preventing chondrocyte death and reducing matrix degradation in both H2O2-treated primary chondrocytes and cartilage tissue from MIA-induced osteoarthritis rats. This was achieved by increasing the levels of aggrecan, collagen type I, collagen type II, TIMP-1, and TIMP-3, while simultaneously decreasing catabolic factors such as phosphorylation of Smad, MMP-3, and MMP-13. Additionally, LMWCP treatment effectively suppressed the activation of inflammation and apoptosis pathways in both LPS-treated primary chondrocytes and cartilage tissue from MIA-induced osteoarthritis rats. These results suggest that LMWCP supplementation ameliorates the progression of osteoarthritis through its direct impact on inflammation and apoptosis in chondrocytes.


[Causes of sudden death during sports activities in Spain].
Sudden death during sports activities has a profound impact on relatives, society, and athletes. Medical screening programs usually fail to prevent sudden death. We report the characteristics of a series of sudden deaths that occurred during sports in Spain. We reviewed cases of sudden death that occurred during sports activities from 1995 to 2001 in the registries of the Institute of Toxicology of Madrid, Spain (Ministry of Justice). The series included 61 cases ranging in age from 11 to 65 years (average 31.9 14.2), 59 males and 2 females. The sports most frequently involved were cycling (21), football (13), and gymnastics (5). The causes of death were atheromatous coronary disease: 25 (40.9%) (23 over 30 years); arrhythmogenic cardiomyopathy: 10 (16.3%) (7 under 30 years); hypertrophic cardiomyopathy: 4 (6.5%); idiopathic left ventricular hypertrophy: 3 (4.9%); postmyocarditis myocardial fibrosis: 2 (3.2%); dilated cardiomyopathy: 1 (1.6%); congenital anomalies in the origin of the coronary arteries: 2 (3.2%); aortic valve disease: 2 (3.2%); and others: 2 (3.2%). In 10 cases (16.3%) (all under 30), the cause of death was undetermined. In 16 cases (26.2%) there was a known pathological antecedent. The disease responsible for death had been diagnosed in only three cases. Arrhythmogenic cardiomyopathy and severe left ventricular hypertrophy were the most common causes of sports-related death in persons under the age of 30. In 30% the cause of death was undetermined. Atheromatous coronary disease was prevalent over the age of 30 years and associated with cycling. Medical screening programs actually in use fail to detect a significant proportion of athletes at risk for sudden death.


A longitudinal study on symptom duration and 60-day clinical course in non-hospitalised COVID-19 cases in Berlin, Germany, March to May, 2020.
BackgroundDetailed information on symptom duration and temporal course of patients with mild COVID-19 was scarce at the beginning of the COVID-19 pandemic.AimWe aimed to determine the longitudinal course of clinical symptoms in non-hospitalised COVID-19 patients in Berlin, Germany.MethodsBetween March and May 2020, 102 confirmed COVID-19 cases in home isolation notified in Berlin, Germany, were sampled using total population sampling. Data on 25 symptoms were collected during telephone consultations (a maximum of four consultations) with each patient. We collected information on prevalence and duration of symptoms for each day of the first 2 weeks after symptom onset and for day 30 and 60 after symptom onset.ResultsMedian age was 35 years (range 18-74), 57% (58/102) were female, and 37% (38/102) reported having comorbidities. During the first 2 weeks, most common symptoms were malaise (94%, 92/98), headache (71%, 70/98), and rhinitis (69%, 68/98). Malaise was present for a median of 11 days (IQR 7-14 days) with 35% (34/98) of cases still reporting malaise on day 14. Headache and muscle pain mostly occurred during the first week, whereas dysosmia and dysgeusia mostly occurred during the second week. Symptoms persisted in 41% (39/95) and 20% (18/88) of patients on day 30 and 60, respectively.ConclusionOur study shows that a significant proportion of non-hospitalised COVID-19 cases endured symptoms for at least 2 months. Further research is needed to assess the frequency of long-term adverse health effects in non-hospitalised COVID-19 patients.


Tracking graphene by fluorescence imaging: a tool for detecting multiple populations of graphene in solution.
Most methods used for the characterization of graphene produced by liquid phase exfoliation require the deposition of the liquid sample on a substrate and subsequent drying. Because of this or other post-synthetic treatments, the reliability of the data in describing the actual features of the graphene particles in the pristine solution becomes questionable. Hence there is a need for new methods that permit the study of graphene directly in solution. Fluorescence imaging is at present the most convenient and sensitive method to visualize nanosized objects in solution. Here we report the development of a new method for visualizing and tracking exfoliated graphene directly in solution using a conventional set-up for fluorescence microscopy. We functionalized a fluorescent surfactant typically used for exfoliating graphite in aqueous phase (Pluronic P123) with two different fluorophores, in order to make graphene detectable by fluorescence microscopy. The photophysical interactions between the fluorescent surfactant and graphene were investigated at the bulk level. Finally, fluorescence microscopy allowed us to track the carbon particles produced and to identify two different populations of particles with sizes of 265 ± 25 and 1100 ± 200 nm respectively. The correlation of these results with TEM and DLS data is discussed.


Prognostic Nomogram for Overall Survival in Patients with Diffuse Large B-Cell Lymphoma.
This study aimed to develop a prognostic nomogram in diffuse large B-cell lymphoma (DLBCL) and compare it with traditional prognostic systems. We included 1,070 consecutive and nonselected patients with DLBCL in the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, between 2006 and 2012. A nomogram based on the Cox proportional hazards model was developed. The entire group were divided into the primary (n = 748) and validation (n = 322) cohorts. The 5-year overall survival (OS) rate was 64.1% for the entire group. Based on a multivariate analysis of the primary cohort, seven independent prognostic factors including age, Ann Arbor stage, Eastern Cooperative Oncology Group performance status score, lactate dehydrogenase, β2-microglobulin, CD5 expression, and Ki-67 index were identified and entered the nomogram. The calibration curve showed the optimal agreement between nomogram prediction and actual observation. In addition, the concordance index (C-index) of the nomogram for OS prediction was 0.77 (95% confidence interval [CI], 0.73-0.81) in the primary cohort and 0.76 (95% CI, 0.70-0.81) in the validation, superior to that of the international prognostic index (IPI), revised IPI (R-IPI), and National Comprehensive Cancer Network (NCCN)-IPI (range, 0.69-0.74, p<.0001). Moreover, in patients receiving rituximab plus CHOP (R-CHOP) or R-CHOP-like regimens, compared with IPI (C-index, 0.73; 95% CI, 0.69-0.77), R-IPI (C-index, 0.70; 95% CI, 0.66-0.74), or NCCN-IPI (C-index, 0.71; 95% CI, 0.66-0.75), the DLBCL-specific nomogram showed a better discrimination capability (p < .0001). The proposed nomogram provided an accurate estimate of survival of patients with DLBCL, especially for those receiving R-CHOP or R-CHOP-like regimens, allowing clinicians to optimized treatment plan based on individualized risk prediction. A diffuse large B-cell lymphoma (DLBCL)-specific prognostic nomogram was developed based on Chinese patients with DLBCL. As a tertiary hospital, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences is the number 1 ranked cancer center in China, with more than 800,000 outpatients in 2018. Patients included in this study were nonselected and came from 29 different provinces, municipalities, and autonomous regions in China. Thus, the data is believed to be representative to an extent.


The chlamydia care cascade of young people attending Australian general practices; a descriptive study to assess gaps in care.
Most chlamydia infections in Australia are diagnosed in general practice. The care cascade concept (testing, treatment and re-testing) can be utilised to explore the management of chlamydia infections. We explored the chlamydia care cascade among young people attending general practices in Australia. We analysed de-identified electronic medical record data for 16-29-year-old individuals attending 70 Australian general practices between January 2018 and December 2020. Five outcomes: (1) chlamydia testing, (2) positivity, (3) treatment, (4) re-testing and (5) re-infection were summarised as annual counts and proportions per calendar year. Logistic regression was used to investigate the association of age, gender and clinic location with each outcome. During the study period, a total of 220909 clinical episodes involving 137358 16-29-year-olds were recorded. Of these episodes, 10.45% (n =23077, 95% CI 8.73-12.46) involved a chlamydia test. Of 1632 chlamydia cases, 88.79% (n =1449, 95% CI 86.37-90.82) had appropriate antibiotics recorded as defined in Australian sexually transmitted infection management guidelines. Of 183 chlamydia cases that did not have appropriate antibiotics recorded, 46.45% (n =85) had re-attended the clinic within 90days of diagnosis. Among 1068 chlamydia cases that had appropriate antibiotic recorded in 2018 and 2019, 22.57% (n =241, 95% CI 20.15-25.18) were re-tested within 6weeks to 4months of their diagnosis. One-third of episodes of chlamydia cases that did not have a re-test recorded (n =281) had re-attended the clinics within 4months of diagnosis. Our study provides insight into chlamydia management by analysing general practice medical records, indicating substantial gaps in testing and re-testing for 16-29-year-olds. These data can also be used to explore the impact of future interventions to optimise chlamydia management.


Comparisons of virulence of influenza virus recombinants in ferrets in relation to their behaviour in man and their genetic constitution.
Two parent viruses, A/Finland/4/74(H3N2) and A/Okuda/57(H2N2), virulent and attenuated respectively for man, showed similar differences of virulence in ferrets as judged by estimations of 50% minimal infectious doses (MID50), the level and persistence of nasal infection, the height and duration of pyrexia and the level of lung infection. In ferrets, two recombinant clones, WRL 94(H3N2) and WRL 105(H3N2), were almost as virulent as A/Finland and indistinguishable from one another, a result which agreed well with genetic analysis (Hay et al. 1977); the RNA pieces of these recombinants appeared identical and largely derived from the virulent parent (A/Finland). The results in ferrets did not agree with tests on clone WRL 94 in small numbers of human volunteers but they were not inconsistent with those on clone WRL 105 in larger numbers. It is possible therefore that careful tests in ferrets may yield more accurate information on the virulence of strains than limited tests in human volunteers. A rapid test for virulence in ferrets is described. It could be used to screen many additional recombinants thereby yielding information on the genetical basis of virulence and indicating possible vaccine strains for more thorough testing in ferrets and in man.


Fallopia japonica, a Natural Modulator, Can Overcome Multidrug Resistance in Cancer Cells.
Resistance of cancer cells to chemotherapy is controlled by the decrease of intracellular drug accumulation, increase of detoxification, and diminished propensity of cancer cells to undergo apoptosis. ATP-binding cassette (ABC) membrane transporters with intracellular metabolic enzymes contribute to the complex and unresolved phenomenon of multidrug resistance (MDR). Natural products as alternative medicine have great potential to discover new MDR inhibitors with diverse modes of action. In this study, we characterized several extracts of traditional Chinese medicine (TCM) plants (N = 16) for their interaction with ABC transporters, cytochrome P3A4 (CYP3A4), and glutathione-S-transferase (GST) activities and their cytotoxic effect on different cancer cell lines. Fallopia japonica (FJ) (Polygonaceae) shows potent inhibitory effect on CYP3A4 P-glycoprotein activity about 1.8-fold when compared to verapamil as positive control. FJ shows significant inhibitory effect (39.81%) compared with the known inhibitor ketoconazole and 100 μg/mL inhibited GST activity to 14 μmol/min/mL. FJ shows moderate cytotoxicity in human Caco-2, HepG-2, and HeLa cell lines; IC50 values were 630.98, 198.80, and 317.37 µg/mL, respectively. LC-ESI-MS were used to identify and quantify the most abundant compounds, emodin, polydatin, and resveratrol, in the most active extract of FJ. Here, we present the prospect of using Fallopia japonica as natural products to modulate the function of ABC drug transporters. We are conducting future study to evaluate the ability of the major active secondary metabolites of Fallopia japonica to modulate MDR and their impact in case of failure of chemotherapy.


Predictors of Mortality by Sex and Race in Heart Failure With Preserved Ejection Fraction: ARIC Community Surveillance Study.
Background Heart failure with preserved ejection fraction (HFpEF) accounts for half of heart failure hospitalizations, with limited data on predictors of mortality by sex and race. We evaluated for differences in predictors of all-cause mortality by sex and race among hospitalized patients with HFpEF in the ARIC (Atherosclerosis Risk in Communities) Community Surveillance Study. Methods and Results Adjudicated HFpEF hospitalization events from 2005 to 2013 were analyzed from the ARIC Community Surveillance Study, comprising 4 US communities. Comparisons between clinical characteristics and mortality at 1 year were made by sex and race. Of 4335 adjudicated acute decompensated heart failure cases, 1892 cases (weighted n=8987) were categorized as HFpEF. Men had an increased risk of 1-year mortality compared with women in adjusted analysis (hazard ratio [HR], 1.27; 95% CI, 1.06-1.52 [P=0.01]). Black participants had lower mortality compared with White participants in unadjusted and adjusted analyses (HR, 0.79; 95% CI, 0.64-0.97 [P=0.02]). Age, heart rate, worsening renal function, and low hemoglobin were associated with increased mortality in all subgroups. Higher body mass index was associated with improved survival in men, with borderline interaction by sex. Higher blood pressure was associated with improved survival among all groups, with significant interaction by race. Conclusions In a diverse HFpEF population, men had worse survival compared with women, and Black participants had improved survival compared with White participants. Age, heart rate, and worsening renal function were associated with increased mortality across all subgroups; high blood pressure was associated with decreased mortality with interaction by race. These insights into sex- and race-based differences in predictors of mortality may help strategize targeted management of HFpEF.


A Difficult Differential Diagnosis of Acute Cholecystitis in a Patient With Steroid-induced Diabetes.
An impairment of gallbladder motility due to autonomic neuropathy may cause cholestasis and result in gallbladder stone formation. Diabetes is one of risk factors for acute cholecystitis. Diabetes and steroid use are associated with the susceptibility to bacterial infections, we are apt to diagnose steroid-induced diabetic patients manifesting symptoms of cholecystitis as having acute bacterial infective cholecystitis. Here, we report a very rare steroid-induced diabetic patient complicated with gallbladder torsion-induced necrotizing cholecystitis due to a floating gallbladder. Cholecystitis; Diabetes; Floating gallbladder; Torsion.


Venous aneurysms: MR diagnosis with the "layered gadolinium" sign.
Our goal was to present MR findings in venous aneurysms and introduce the "layered gadolinium" sign as an ancillary diagnostic finding. Gadolinium-enhanced MR images of three patients with retroperitoneal venous aneurysms were retrospectively reviewed. Prior to MRI, venous aneurysm had been suspected clinically in only one patient. Surgical correlation was available in one patient. A phantom was constructed and imaged to investigate the cause of the layered gadolinium sign. A gradation of signal intensity, the layered gadolinium sign, was observed in three patients with venous aneurysms on postcontrast T1-weighted images. The anterior portion of the aneurysms demonstrated high signal intensity separated by a sharp interface from the low signal intensity posterior region. Unenhanced time-of-flight MR venography, color Doppler, and duplex sonography failed to demonstrate flow in the patient with surgical proof. The layered gadolinium sign may be helpful in the diagnosis of venous aneurysm and in differentiating these masses from solid neoplasms.


Encapsulation in Cell Therapy: Methodologies, Materials, and Clinical Applications.
The clinical application of cells and the development of new delivery systems have allowed significant advances in the field of cell therapy and encapsulation in recent years. The ability to combine cells and biocompatible matrices in the encapsulation of cells providing long-term delivery has provides new therapeutic alternatives in the development of new therapies. A structured search of bibliographic databases was carried out to determine the entire methodology related to cell encapsulation with clinical application. Cell encapsulation provides increased retention time in the target tissue improving its therapeutic efficacy. This technology involves the development of a physical barrier (natural or synthetic matrix surrounded by a semipermeable membrane) to isolate and protect cells from the host's immune system maintaining the microenvironment of embedded cells, their viability and their capacity of differentiation, improving their function in vivo, and reducing side effects associated with the use of immunosuppressive therapy. The purpose of this review is to discuss the different technologies of cell encapsulation and the different materials utilized from both, natural and synthetic origin, and provide an overview of current therapeutic applications of cell encapsulation, as well as, the perspectives for their clinical application including as a novelty the current application in clinical trials.


Picomolar gradients of progesterone select functional human sperm even in subfertile samples.
More than 1 million infertility treatments are practiced around the world per year, but only 30% of the couples succeed in taking a baby home. Reproductive technology depends in part on sperm quality, which influences not only fertilization but also embryo development and implantation. In order to provide a better quality sperm subpopulation, innovative sperm selection techniques based on physiological sperm features are needed. Spermatozoa at an optimum state may be selected by following an increasing concentration gradient of picomolar progesterone, a steroid secreted by the cumulus cells at the time of ovulation. In this study we developed a method to recruit spermatozoa at the best functional state, based on sperm guidance toward progesterone. The sperm selection assay (SSA) consists of a device with two wells connected by a tube. One well was filled with the sperm suspension and the other with picomolar progesterone, which diffused inside the connecting tube as a gradient. The sperm quality after the SSA was analyzed in normal and subfertile semen samples. Several sperm parameters indicative of sperm physiological state were determined before and after the SSA: capacitation, DNA integrity and oxidative stress. After the SSA, the mean level of capacitated spermatozoa increased three times in normal and in subfertile samples. The level of sperm with intact DNA was significantly increased, while sperm oxidative stress was decreased after sperm selection. Interestingly, the exposure to a progesterone gradient stimulated the completion of capacitation in some spermatozoa that could not do it by themselves. Thus, the SSA supplies a sperm population enriched with spermatozoa at an optimum physiological state that may improve the assisted reproductive technology outcome.


Dynapenic Obesity and Prevalence of Type 2 Diabetes in Middle-Aged Japanese Men.
The independent and combined associations of muscle strength and obesity on the prevalence of type 2 diabetes in Japanese men remain unclear. Hand grip strength was cross-sectionally evaluated between 2011 and 2013 to assess muscle strength in 5039 male workers aged 40 to 64 years. Weight and height were measured, and overweight/obesity was defined as a body mass index ≥25 kg/m(2). The prevalence of type 2 diabetes, defined as fasting plasma glucose ≥126 mg/dL and/or hemoglobin A1c ≥6.5% and/or self-reported physician-diagnosed diabetes, was evaluated. Odds ratios (OR) and 95% confidence intervals (95% CI) for the prevalence of type 2 diabetes were obtained using a logistic regression model. In total, 611 participants had type 2 diabetes, and 1763 participants were overweight/obese. After adjustment for covariates, we found an inverse association between muscle strength and the prevalence of type 2 diabetes (P for trend <0.01). In addition, when the analyses were stratified by obesity status, the multivariable-adjusted OR per 2-standard-deviation increase in muscle strength was 0.64 (95% CI, 0.49-0.83) in the overweight/obese group, compared to a weaker relationship in the normal-weight group (OR 0.79 per 2-standard-deviation increase; 95% CI, 0.60-1.06). Dynapenia, an age-related decrease in muscle strength, is associated with increased prevalence of type 2 diabetes, and this relationship is stronger in overweight/obese middle-aged Japanese men than in normal-weight men.


Peripheral but crucial: a hydrophobic pocket (Tyr(706), Leu(337), and Met(336)) for potent and selective inhibition of neuronal nitric oxide synthase.
Selective inhibition of the neuronal isoform of nitric oxide synthase (nNOS) over endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) has become a promising strategy for the discovery of new therapeutic agents for neurodegenerative diseases. However, because of the high sequence homology of different isozymes in the substrate binding pocket, developing inhibitors with both potency and excellent isoform selectivity remains a challenging problem. Herein, we report the evaluation of a recently discovered peripheral hydrophobic pocket (Tyr(706), Leu(337), and Met(336)) that opens up upon inhibitor binding and its potential in designing potent and selective nNOS inhibitors using three compounds, 2a, 2b, and 3. Crystal structure results show that inhibitors 2a and 3 adopted the same binding mode as lead compound 1. We also found that hydrophobic interactions between the 4-methyl group of the aminopyridine ring of these compounds with the side chain of Met(336), as well as the π-π stacking interaction between the pyridinyl motif and the side chain of Tyr(706) are important for the high potency and selectivity of these nNOS inhibitors.


Signaling by the angiotensin-converting enzyme.
Inhibition of the angiotensin-converting enzyme (ACE) protects against the progression of several cardiovascular diseases. Because of its dual role in regulating angiotensin II and bradykinin levels, the positive clinical effects of ACE inhibitors were thought to be the consequence of concomitant reductions in the production of angiotensin II and the degradation of bradykinin. Recent evidence suggests that some of the beneficial effects of ACE inhibitors on cardiovascular function and homeostasis can be attributed to novel mechanisms. These include the accumulation of the ACE substrate N-acetyl-seryl-aspartyl-lysyl-proline, which blocks collagen deposition in the injured heart, as well as the activation of an ACE signaling cascade that involves the activation of the kinase CK2 and the c-Jun N-terminal kinase in endothelial cells and leads to changes in gene expression. Moreover, at least one other ACE homologue (ACE2) is proposed to counteract the detrimental effects associated with the activation of the classical renin-angiotensin system. These data reveal hitherto unexpected levels of internal regulation of the renin-angiotensin system.


CAMKK2 regulates mitochondrial function by controlling succinate dehydrogenase expression, post-translational modification, megacomplex assembly, and activity in a cell-type-specific manner.
The calcium (Ca2+)/calmodulin (CAM)-activated kinase kinase 2 (CAMKK2)-signaling regulates several physiological processes, for example, glucose metabolism and energy homeostasis, underlying the pathogenesis of metabolic diseases. CAMKK2 exerts its biological function through several downstream kinases, therefore, it is expected that depending on the cell-type-specific kinome profile, the metabolic effects of CAMKK2 and its underlying mechanism may differ. Identification of the cell-type-specific differences in CAMKK2-mediated glucose metabolism will lead to unravelling the organ/tissue-specific role of CAMKK2 in energy metabolism. Therefore, the objective of this study was to understand the cell-type-specific regulation of glucose metabolism, specifically, respiration under CAMKK2 deleted conditions in transformed human embryonic kidney-derived HEK293 and hepatoma-derived HepG2 cells. Cellular respiration was measured in terms of oxygen consumption rate (OCR). OCR and succinate dehydrogenase (SDH) enzyme activity were measured following the addition of substrates. In addition, transcription and proteomic and analyses of the electron transport system (ETS)-associated proteins, including mitochondrial SDH protein complex (complex-II: CII) subunits, specifically SDH subunit B (SDHB), were performed using standard molecular biology techniques. The metabolic effect of the altered SDHB protein content in the mitochondria was further evaluated by cell-type-specific knockdown or overexpression of SDHB. CAMKK2 deletion suppressed cellular respiration in both cell types, shifting metabolic phenotype to aerobic glycolysis causing the Warburg effect. However, isolated mitochondria exhibited a cell-type-specific enhancement or dampening of the respiratory kinetics under CAMKK2 deletion conditions. This was mediated in part by the cell-type-specific effect of CAMKK2 loss-of-function on transcription, translation, post-translational modification (PTM), and megacomplex assembly of nuclear-encoded mitochondrial SDH enzyme complex subunits, specifically SDHB. The cell-type-specific increase or decrease in SDHs protein levels, specifically SDHB, under CAMKK2 deletion condition resulted in an increased or decreased enzymatic activity and CII-mediated respiration. This metabolic phenotype was reversed by cell-type-specific knockdown or overexpression of SDHB in respective CAMKK2 deleted cell types. CAMKK2 loss-of-function also affected the overall assembly of mitochondrial supercomplex involving ETS-associated proteins in a cell-type-specific manner, which correlated with differences in mitochondrial bioenergetics. This study provided novel insight into CAMKK2-mediated cell-type-specific differential regulation of mitochondrial function, facilitated by the differential expression, PTMs, and assembly of SDHs into megacomplex structures. Video Abstract.


[Violence and accidents among older and younger adults: evidence from the Surveillance System for Violence and Accidents (VIVA), Brazil].
Data from the Brazilian Surveillance System for Violence and Accidents (VIVA) in 2009 were used to examine socio-demographic characteristics, outcomes, and types of accidents and violence treated at 74 sentinel emergency services in 23 Brazilian State capitals and the Federal District. The analysis included 25,201 individuals aged > 20 years (10.1% > 60 years); 89.3% were victims of accidents and 11.9% victims of violence. Hospitalization was the outcome in 11.1% of cases. Compared to the general population, there were more men and non-white individuals among victims of accidents, and especially among victims of violence. As compared to younger adults (20-59 years), accidents and violence against elderly victims showed less association with alcohol, a higher proportion of domestic incidents, more falls and pedestrian accidents, and aggression by family members. Policies for the prevention of accidents and violence should consider the characteristics of these events in the older population.


Can genetic variability for nitrogen metabolism in the developing ear of maize be exploited to improve yield?
Quantitative trait loci (QTLs) for the main steps of nitrogen (N) metabolism in the developing ear of maize (Zea mays L.) and their co-localization with QTLs for kernel yield and putative candidate genes were searched in order to identify chromosomal regions putatively involved in the determination of yield. During the grain-filling period, the changes in physiological traits were monitored in the cob and in the developing kernels, representative of carbon and N metabolism in the developing ear. The correlations between these physiological traits and traits related to yield were examined and localized with the corresponding QTLs on a genetic map. Glycine and serine metabolism in developing kernels and the cognate genes appeared to be of major importance for kernel production. The importance of kernel glutamine synthesis in the determination of yield was also confirmed. The genetic and physiological bases of N metabolism in the developing ear can be studied in an integrated manner by means of a quantitative genetic approach using molecular markers and genomics, and combining agronomic, physiological and correlation studies. Such an approach leads to the identification of possible new regulatory metabolic and developmental networks specific to the ear that may be of major importance for maize productivity.


DiOC6 staining reveals organelle structure and dynamics in living yeast cells.
When present at low concentrations, the fluorescent lipophilic dye, DiOC6, stains mitochondria in living yeast cells [Pringle et al.: Methods in Cell Biol. 31:357-435, 1989; Weisman et al.: Proc. Natl. Acad. Sci. U.S.A. 87:1076-1080, 1990]. However, we found that the nuclear envelope and endoplasmic reticulum were specifically stained if the dye concentration was increased or if certain respiratory-deficient yeast strains were examined. The quality of nuclear envelope staining with DiOC6 was sufficiently sensitive to reveal alterations in the nuclear envelope known as karmellae. These membranes were previously apparent only by electron microscopy. At the high dye concentrations required to stain the nuclear envelope, wild-type cells could no longer grow on non-fermentable carbon sources. In spite of this effect on mitochondrial function, the presence of high dye concentration did not adversely affect cell viability or general growth characteristics when strains were grown under standard conditions on glucose. Consequently, time-lapse confocal microscopy was used to examine organelle dynamics in living yeast cells stained with DiOC6. These in vivo observations correlated very well with previous electron microscopic studies, including analyses of mitochondria, karmellae, and mitosis. For example, cycles of mitochondrial fusion and division, as well as the changes in nuclear shape and position that occur during mitosis, were readily imaged in time-lapse studies of living DiOC6-stained cells. This technique also revealed new aspects of nuclear disposition and interactions with other organelles. For example, the nucleus and vacuole appeared to form a structurally coupled unit that could undergo coordinated movements. Furthermore, unlike the general view that nuclear movements occur only in association with division, the nucleus/vacuole underwent dramatic migrations around the cell periphery as cells exited from stationary phase. In addition to the large migrations or rotations of the nucleus/vacuole, DiOC6 staining also revealed more subtle dynamics, including the forces of the spindle on the nuclear envelope during mitosis. This technique should have broad application in analyses of yeast cell structure and function.


Phonological working memory and central executive function differ in children with typical development and dyslexia.
The primary purpose of this study was to compare the working memory performance of monolingual English-speaking second- grade children with dyslexia (N = 82) to second-grade children with typical development (N = 167). Prior to making group comparisons, it is important to demonstrate invariance between working memory models in both groups or between-group comparisons would not be valid. Thus, we completed invariance testing using a model of working memory that had been validated for children with typical development (Gray et al., 2017) to see if it was valid for children with dyslexia. We tested three types of invariance: configural (does the model test the same constructs?), metric (are the factor loadings equivalent?), and scalar (are the item intercepts the same?). Group comparisons favoured the children with typical development across all three working memory factors. However, differences in the Focus-of-Attention/Visuospatial factor could be explained by group differences in non-verbal intelligence and language skills. In contrast, differences in the Phonological and Central Executive working memory factors remained, even after accounting for non-verbal intelligence and language. Results highlight the need for researchers and educators to attend not only to the phonological aspects of working memory in children with dyslexia, but also to central executive function.


Virtual reality for autism communication and education, with lessons for medical training simulators.
This study is adapting Virtual Reality (VR) technologies to teach children with autism new coping skills that may then be generalized in their everyday lives. It helps to understand that children with autism are challenged by a sensory overload and by aversions to a variety of auditory, visual, and tactile stimuli. In addition, their ability to attenuate and/or ignore these stimuli differs from that of the "typical" child. Therefore, our goals were to: 1. assess the potential of each of the children (both with and without verbal skills) for sustained interaction with task environments, 2. to identify which visual, auditory, and kinetic VR components would be attractive to our test group, 3. to identify each child's ability to attenuate and/or ignore a variety of distractors, and 4. to build new "pivotal behaviors" [2] for learning. These pivotal behaviors include: improvement of time-on-task, meaningful and consistent interaction with the real world, and screening out extraneous environmental stimuli. Our findings to date have been very encouraging, and we will continue to investigate the role of VR as a tool for generalized learning and the modification of pivotal behaviors. This ongoing study also provides technology transfer of communications applications from government, universities and businesses out into telemedicine and elementary schools.


Evolving spiking neural networks for audiovisual information processing.
This paper presents a new modular and integrative sensory information system inspired by the way the brain performs information processing, in particular, pattern recognition. Spiking neural networks are used to model human-like visual and auditory pathways. This bimodal system is trained to perform the specific task of person authentication. The two unimodal systems are individually tuned and trained to recognize faces and speech signals from spoken utterances, respectively. New learning procedures are designed to operate in an online evolvable and adaptive way. Several ways of modelling sensory integration using spiking neural network architectures are suggested and evaluated in computer experiments.


Exhibiting Good Health: Public Health Exhibitions in London, 1948-71.
This article examines the changing nature of public health services and their relationship with the public in post-war Britain by an analysis of the exhibitions mounted by Medical Officers of Health (MOsH) in London. Focusing on the period 1948-71, the article explores a time when public health practice, and the problems it faced, were in flux. A decline in infectious disease and an increase in chronic conditions linked to lifestyle required a new role for public health services. Exhibitions were one of several methods that MOsH used to inform the public about dangers to their health, but also to persuade them to change their behaviour. The exhibition, though, offers a unique insight into the relationship between public health authorities and the public, as exhibitions brought MOsH into direct contact with people. It is suggested that in the MOsH exhibitions we can find signs of a new relationship between public health practitioners and the public. Whilst elements of the pre-war, often moralistic ideology of public health services could still be detected, there is also evidence of a more nuanced, responsive dynamic between practitioners and the people. By the end of the 1960s, 'the public' was increasingly being thought of as a collection of 'publics', including individuals, target groups and vocal respondents.


Electrical stimulation and wound healing.
Living tissues possess direct current surface electropotentials that regulate, at least in part, the healing process. Following tissue damage, a current of injury is generated that is thought to trigger biological repair. In addition, exogenous electrical stimuli have been shown to enhance the healing of wounds in both human subjects and animal models. Intractable ulcers have demonstrated accelerated healing and skin wounds have resurfaced faster and with better tensile properties following exposure to electrical currents. This article examines the bioelectric properties of living systems and reviews the existing literature on electrical stimulation and wound healing.


Biomedical question answering using semantic relations.
The proliferation of the scientific literature in the field of biomedicine makes it difficult to keep abreast of current knowledge, even for domain experts. While general Web search engines and specialized information retrieval (IR) systems have made important strides in recent decades, the problem of accurate knowledge extraction from the biomedical literature is far from solved. Classical IR systems usually return a list of documents that have to be read by the user to extract relevant information. This tedious and time-consuming work can be lessened with automatic Question Answering (QA) systems, which aim to provide users with direct and precise answers to their questions. In this work we propose a novel methodology for QA based on semantic relations extracted from the biomedical literature. We extracted semantic relations with the SemRep natural language processing system from 122,421,765 sentences, which came from 21,014,382 MEDLINE citations (i.e., the complete MEDLINE distribution up to the end of 2012). A total of 58,879,300 semantic relation instances were extracted and organized in a relational database. The QA process is implemented as a search in this database, which is accessed through a Web-based application, called SemBT (available at http://sembt.mf.uni-lj.si ). We conducted an extensive evaluation of the proposed methodology in order to estimate the accuracy of extracting a particular semantic relation from a particular sentence. Evaluation was performed by 80 domain experts. In total 7,510 semantic relation instances belonging to 2,675 distinct relations were evaluated 12,083 times. The instances were evaluated as correct 8,228 times (68%). In this work we propose an innovative methodology for biomedical QA. The system is implemented as a Web-based application that is able to provide precise answers to a wide range of questions. A typical question is answered within a few seconds. The tool has some extensions that make it especially useful for interpretation of DNA microarray results.


Fine-scale spatial genetic structure across the species range reflects recent colonization of high elevation habitats in silver fir (Abies alba Mill.).
Variation in genetic diversity across species ranges has long been recognized as highly informative for assessing populations' resilience and adaptive potential. The spatial distribution of genetic diversity within populations, referred to as fine-scale spatial genetic structure (FSGS), also carries information about recent demographic changes, yet it has rarely been connected to range scale processes. We studied eight silver fir (Abies alba Mill.) population pairs (sites), growing at high and low elevations, representative of the main genetic lineages of the species. A total of 1,368 adult trees and 540 seedlings were genotyped using 137 and 116 single nucleotide polymorphisms (SNPs), respectively. Sites revealed a clear east-west isolation-by-distance pattern consistent with the post-glacial colonization history of the species. Genetic differentiation among sites (FCT = 0.148) was an order of magnitude greater than between elevations within sites (FSC = 0.031), nevertheless high elevation populations consistently exhibited a stronger FSGS. Structural equation modelling revealed that elevation and, to a lesser extent, post-glacial colonization history, but not climatic and habitat variables, were the best predictors of FSGS across populations. These results suggest that high elevation habitats have been colonized more recently across the species range. Additionally, paternity analysis revealed a high reproductive skew among adults and a stronger FSGS in seedlings than in adults, suggesting that FSGS may conserve the signature of demographic changes for several generations. Our results emphasize that spatial patterns of genetic diversity within populations provide information about demographic history complementary to non-spatial statistics, and could be used for genetic diversity monitoring, especially in forest trees.


Cloning and characterization of the structural gene for the class 2 protein of Neisseria meningitidis.
The class 2 protein of Neisseria meningitidis is the major outer membrane protein and a porin. A lambda gt11 bank of meningococcal chromosomal DNA was screened with monoclonal antibodies against gonococcal protein IB that cross-react with meningococcal class 2 protein. Three independent immunoreactive clones were isolated. DNA sequence analysis indicated that these clones included regions encoding the N-terminal portion of the class 2 protein. An oligonucleotide of 21 bases that was complementary to this sequence was synthesized and used as a probe for a second screening of the lambda gt11 bank. One of the positive clones isolated contained the complete gene, including the ribosome binding site, but lacked the promoter region. On the basis of the DNA sequence, a protein of 360 amino acids was predicted. Comparison of the predicted protein sequence with that of gonococcal protein I showed little homology in six regions constituting 29% of the total amino acids, while the remainder of the coding frame showed 81% homology of amino acid residues. The DNA homology in the immediate 5' and 3' noncoding sequences was very striking. Following the putative transcription terminator, the 3' DNA sequence contained a complex pattern of direct and inverted repeats having some similarity to the 3' sequence of the gonococcal protein IB gene and very close homology to a sequence located in the pilS1 region (R. Haas and T. F. Meyer, Cell 44:107, 1986), an area of the gonococcal genome containing silent pilin genes.


Predicting Postoperative Sagittal Plane Alignment of the Foot Using Intraoperative Simulated Weightbearing Lateral Imaging During Flatfoot Reconstructive Surgery: A Short-Term Retrospective Analysis.
The sagittal plane relationship of the hindfoot and midfoot joints is a primary determinant of proper alignment in flatfoot reconstructive surgery as assessed both clinically and on postoperative weightbearing (WB) lateral radiographs. The traditional approach to intraoperative radiographic imaging allows for accurate assessment of fixation placement but only a crude evaluation of final sagittal plane alignment. Surgeons employ various methods in an attempt to load the foot during lateral imaging. Skepticism exists regarding the ability of simulated WB fluoroscopy to predict the final outcome, and evidence is lacking to support this practice. A retrospective investigation was performed assessing the correlation of Meary's angle, calcaneal inclination angle, and calcaneal-1st metatarsal angle as demonstrated on intraoperative simulated WB lateral foot imaging to 10- week postoperative full WB lateral radiographs. A consistent simulated WB imaging protocol was used with 46 consecutive cases of flatfoot reconstruction in this analysis of secular trends. The average change in Meary's angle between intraoperative simulated WB and postoperative full WB was -1.09° with 89% of cases within ±5°. The average change in calcaneal-1st metatarsal angle between intraoperative simulated WB and full WB was -2.61° with 85% of cases within ±5°. The average change in calcaneal inclination angle between intraoperative simulated WB and full WB was -2.62° with 88% of cases within ±5°. These findings confirm the clinical utility of intraoperative simulated WB lateral imaging as a useful tool in predicting the postoperative sagittal plane alignment of the midfoot and rearfoot in patients undergoing flatfoot reconstructive surgery.


Childhood predictors of adult adiposity: findings from a longitudinal study.
The increasing prevalence of overweight and obesity has become a key challenge for New Zealand. The purpose of the present study was to examine childhood risk factors for adult adiposity in a longitudinal birth cohort. Data were gathered from the Christchurch Health and Development Study (CHDS), a birth cohort of 1,265 children born in Christchurch in 1977. Associations were examined between socio-demographic background, perinatal factors, infant and child characteristics, family functioning/child maltreatment and adiposity at ages 30 and 35 years. Adiposity was assessed using body mass index scores. At ages 30 and 35, approximately one-third of cohort members were overweight and one-fifth were obese. Generalised estimating equation models showed that statistically significant (p<.05) predictors of later adiposity and overweight/obesity were: male gender, being born into a single-parent family, having parents with larger body size, higher early infant growth, limited or no breastfeeding, lower levels of cognitive ability and exposure to severe sexual abuse. Overweight and obesity was associated with social and family background, biological endowment, cognitive ability and childhood adversity factors. These findings may assist in the development of structured adiposity intervention programmes in conjunction with established community organisations specialising in child and family health.


A model for genome size evolution.
We present a model for genome size evolution that takes into account both local mutations such as small insertions and small deletions, and large chromosomal rearrangements such as duplications and large deletions. We introduce the possibility of undergoing several mutations within one generation. The model, albeit minimalist, reveals a non-trivial spontaneous dynamics of genome size: in the absence of selection, an arbitrary large part of genomes remains beneath a finite size, even for a duplication rate 2.6-fold higher than the rate of large deletions, and even if there is also a systematic bias toward small insertions compared to small deletions. Specifically, we show that the condition of existence of an asymptotic stationary distribution for genome size non-trivially depends on the rates and mean sizes of the different mutation types. We also give upper bounds for the median and other quantiles of the genome size distribution, and argue that these bounds cannot be overcome by selection. Taken together, our results show that the spontaneous dynamics of genome size naturally prevents it from growing infinitely, even in cases where intuition would suggest an infinite growth. Using quantitative numerical examples, we show that, in practice, a shrinkage bias appears very quickly in genomes undergoing mutation accumulation, even though DNA gains and losses appear to be perfectly symmetrical at first sight. We discuss this spontaneous dynamics in the light of the other evolutionary forces proposed in the literature and argue that it provides them a stability-related size limit below which they can act.


Interventions to address cancer-related financial toxicity: Recommendations from the field.
Addressing financial toxicity among cancer patients is a complex process that requires a multifaceted approach, particularly for rural patients who may face additional cost-related barriers to care. In this study, we examined interventions being implemented by financial navigation staff at various cancer centers that help address financial toxicity experienced by oncology patients. We conducted semistructured interviews with a convenience sample of financial navigation staff across 29 cancer centers in both rural and urban areas in 7 states. Interviews were audio-recorded and transcribed. Descriptive coding and thematic analysis techniques were used to analyze the data. Thirty-five participants were interviewed, the majority of whom worked in cancer centers located in rural counties. Participants identified the use of screening tools, patient education, and access to tailored financial assistance resources as best practices. Immediate resource needs included additional financial navigation staff, including lay navigators and community health workers, to promote linkages to local resources. Suggested clinical areas for intervention included proactive and early implementation of financial assessments and discussions between providers and patients, along with training and access to regularly updated resources for those in financial navigator/counselor roles. Participants also discussed the need for policy-level interventions to reform health systems (including employment protections) and health insurance programs. Implementing proactive methods to screen for and address financial needs of patients is essential to improving cancer-related outcomes. Additional programs and research are needed to help establish systematic and standardized methods to enhance financial navigation services, especially for underserved rural communities.


Antibacterial and antifouling polymer brushes incorporating antimicrobial peptide.
Surface-initiated atom transfer radical polymerization (ATRP) has been used to prepare antifouling copolymer brushes based on 2-(2-methoxyethoxy)ethyl methacrylate (MEO(2)MA) and hydroxyl-terminated oligo(ethylene glycol) methacrylate (HOEGMA). The amount of hydroxyl reactive groups incorporated into the brushes was varied by changing the composition of the monomer mixture. These coatings were subsequently functionalized by a natural antibacterial peptide, magainin I, via an oriented chemical grafting on hydroxyl groups, which maintains the activity of the peptide. The antibacterial activity of the functionalized brushes was successfully tested against two different strains of gram-positive bacteria.


Sacran Hydrogel Film Containing Keratinocyte Growth Factor Accelerates Wound Healing by Stimulating Fibroblast Migration and Re-epithelization.
Regenerative therapy with keratinocyte growth factor (KGF) is a novel therapeutic approach for treatment of chronic wounds. However, KGF cannot be used directly to the wound site due to its physicochemical instability. In previous study, sacran, a natural megamolecular polysaccharide, showed potential properties as a biomaterial for hydrogel film in wound healing. In this study, we fabricated sacran hydrogel film containing KGF (Sac/KGF-HF) and evaluated the effects of Sac/KGF-HF on fibroblasts migration and re-epithelialization process. We successfully prepared a homogenous and -amorphous Sac/KGF-HF by a casting method. In addition, Sac/KGF-HF had a high swelling ratio and flexibility. Sac/KGF-HF promoted a migration process of NIH3T3 cells and improved wound healing ability in mice with a percentage of wound closure reaching 90.4% at 9 d. Interestingly, the addition of KGF in Sac-HF considerably increased the number of epithelial cells compared to control, which is important in the re-epithelialization process. It could be concluded that KGF in Sac-HF has the potential for promoting Sac-HF abilities in wound healing process.


Prevalence, Risk Factors, and Genetic Characterization of Extended-Spectrum Beta-Lactamase Escherichia coli Isolated From Healthy Pregnant Women in Madagascar.
Antimicrobial resistance is a major public health concern worldwide affecting humans, animals and the environment. However, data is lacking especially in developing countries. Thus, the World Health Organization developed a One-Health surveillance project called Tricycle focusing on the prevalence of ESBL-producing Escherichia coli in humans, animals, and the environment. Here we present the first results of the human community component of Tricycle in Madagascar. From July 2018 to April 2019, rectal swabs from 492 pregnant women from Antananarivo, Mahajanga, Ambatondrazaka, and Toamasina were tested for ESBL-E. coli carriage. Demographic, sociological and environmental risk factors were investigated, and E. coli isolates were characterized (antibiotic susceptibility, resistance and virulence genes, plasmids, and genomic diversity). ESBL-E. coli prevalence carriage in pregnant women was 34% varying from 12% (Toamasina) to 65% (Ambatondrazaka). The main risk factor associated with ESBL-E. coli carriage was the rainy season (OR = 2.9, 95% CI 1.3-5.6, p = 0.009). Whole genome sequencing was performed on 168 isolates from 144 participants. bla CTX-M-15 was the most frequent ESBL gene (86%). One isolate was resistant to carbapenems and carried the bla NDM-5 gene. Most isolates belonged to commensalism associated phylogenetic groups A, B1, and C (90%) and marginally to extra-intestinal virulence associated phylogenetic groups B2, D and F (10%). Multi locus sequence typing showed 67 different sequence types gathered in 17 clonal complexes (STc), the most frequent being STc10/phylogroup A (35%), followed distantly by the emerging STc155/phylogroup B1 (7%), STc38/phylogroup D (4%) and STc131/phylogroup B2 (3%). While a wide diversity of clones has been observed, SNP analysis revealed several genetically close isolates (n = 34/168) which suggests human-to-human transmissions. IncY plasmids were found with an unusual prevalence (23%), all carrying a bla CTX-M-15. Most of them (85%) showed substantial homology (≥85%) suggesting a dissemination of IncY ESBL plasmids in Madagascar. This large-scale study reveals a high prevalence of ESBL-E. coli among pregnant women in four cities in Madagascar associated with warmth and rainfall. It shows the great diversity of E. coli disseminating throughout the country but also transmission of specific clones and spread of plasmids. This highlights the urgent need of public-health interventions to control antibiotic resistance in the country.


Intrafamilial person-to-person spread of bacillary dysentery due to Shigella dysenteriae in southwestern Saudi Arabia.
To identify the factors that influence transmission of bacillary dysentry (BD) within families during a propagated outbreak of bacillary dysentery. A retrospective cohort study. Eighteen neighbouring villages in rural Gizan, southwestern Saudi Arabia. Two hundred and thirty three cases of BD were identified among seventy nine families. Secondary cases of BD occurred in 57 of 79 families with a primary case of BD. The secondary attack rate per cent (AR%) within families ranged between 7.7% and 80%. Age of primary cases did not correlate with degree of secondary AR% in exposed families (p > 0.04; p > 0.05); however, within households, the age of the first secondary cases (median = two years) was usually less than the age of the primary case (median = six years). Children under five years of age constituted 43% of secondary cases. The median interval between successive cases within a house ranged from three and seven days. Two hundred and twenty cases (94.4%) gave history of close contact within another case of BD. Cases of BD were exposed to close relatives with BD (79.1%), neighbours (11.4%), and friends (9.5%). Risk factors influencing the spread of BD within families included two rooms or fewer per house (OR = 4.3, 9.5% CI 1.3-14.3), family size of five or more (p = 0.012, two-tailed Fisher's exact test), and presence of more than two persons per room (OR = 11.2, 95% CI 3.1-42.4). Person-to-person secondary transmission can amplify the spread of bacillary dysentery within households and neighbouring villages. Crowding was a risk factor that amplified transmission of BD within families.


Bronchiolitis obliterans organizing pneumonia.
Bronchiolitis obliterans organizing pneumonia (BOOP) is a diffuse infiltrative pulmonary disorder that has an insidious onset. The patient often presents with flu-like symptoms and radiological findings showing bilateral patchy infiltrates. Histological features show fibromyxoid connective tissue plugs that are evenly spaced in small distal airways and alveolar spaces. Treatment for BOOP is corticosteroid therapy. Critical care nurses must be cognizant of BOOP as a differential diagnosis for patients for whom antibiotic therapy has not resolved symptoms.