Mechanisms of Exercise Limitation and Prevalence of Pulmonary Hypertension in Pulmonary Langerhans Cell Histiocytosis.
Pulmonary Langerhans cell histiocytosis (PLCH) determines reduced exercise capacity. The speculated mechanisms of exercise impairment in PLCH are ventilatory and cardiocirculatory limitations, including pulmonary hypertension (PH). What are the mechanisms of exercise limitation, the exercise capacity, and the prevalence of dynamic hyperinflation (DH) and PH in PLCH? In a cross-sectional study, patients with PLCH underwent an incremental treadmill cardiopulmonary exercise test with an evaluation of DH, pulmonary function tests, and transthoracic echocardiography. Those patients with lung diffusing capacity for carbon monoxide (Dlco) < 40% predicted and/or transthoracic echocardiogram with tricuspid regurgitation velocity > 2.5 m/s and/or with indirect PH signs underwent right heart catheterization. Thirty-five patients were included (68% women; mean age, 47 ± 11 years). Ventilatory and cardiocirculatory limitations, impairment suggestive of PH, and impaired gas exchange occurred in 88%, 67%, 29%, and 88% of patients, respectively. The limitation was multifactorial in 71%, exercise capacity was reduced in 71%, and DH occurred in 68% of patients. FEV1 and Dlco were 64 ± 22% predicted and 56 ± 21% predicted. Reduction in Dlco, an obstructive pattern, and air trapping occurred in 80%, 77%, and 37% of patients. FEV1 and Dlco were good predictors of exercise capacity. The prevalence of PH was 41%, predominantly with a precapillary pattern, and mean pulmonary artery pressure correlated best with FEV1 and tricuspid regurgitation velocity. PH is frequent and exercise impairment is common and multifactorial in PLCH. The most prevalent mechanisms are ventilatory, cardiocirculatory, and suggestive of PH limitations. ClinicalTrials.gov; No.: NCT02665546; URL: www.clinicaltrials.gov.


Disruption of mitochondrial respiration inhibits volume-regulated anion channels and provokes neuronal cell swelling.
Hypoxia and inhibitors of mitochondrial respiration impair the regulatory volume decrease (RVD) of cerebellar granule neurons after hypotonic swelling. RVD is linked to the opening of volume-regulated anion channels (VRACs). VRACs are outwardly rectifying, inactivate slowly during maintained depolarization, and are permeable to the cellular organic osmolyte taurine. Channel activation requires nonhydrolytic ATP binding and is not modulated by intracellular ADP. VRAC opening is reversibly depressed by hypoxia and by mitochondrial inhibitors such as oligomycin, rotenone, and antimycin A. These results demonstrate that neuronal VRAC activation and swelling are both tightly linked to cellular energy. Moreover, the findings reported in this work may have a particular significance for inherited mitochondrial human diseases, such as mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), which cause brain swelling and edema.


Potential impact of global warming on deciduous oak dieback caused by ambrosia fungus Raffaelea sp. carried by ambrosia beetle Platypus quercivorus (Coleoptera: Platypodidae) in Japan.
Deciduous oak dieback in Japan has been known since the 1930s, but in the last ten years epidemics have intensified and spread to the island's western coastal areas. The symbiotic ambrosia fungus Raffaelea sp. is the causal agent of oak dieback, and is vectored by Platypus quercivorus (Murayama). This is the first example of an ambrosia beetle fungus that kills vigorous trees. Mortality of Quercus crispula was approximately 40% but much lower for associated species of Fagaceae, even though each species had a similar number of beetle attacks. It is likely that other oaks resistant to the fungus evolved under a stable relationship between the tree, fungus and beetle during a long evolutionary process. Quercus crispula was probably not part of this coevolution. This hypothesis was supported by the fact that P. quercivorus showed the least preference for Q. crispula yet exhibited highest reproductive success in this species. Therefore, P. quercivorus could spread more rapidly in stands with a high composition of Q. crispula. The present oak dieback epidemic in Japan probably resulted from the warmer climate that occurred from the late 1980s which made possible the fateful encounter of P. quercivorus with Q. cripsula by allowing the beetle to extend its distribution to more northerly latitudes and higher altitudes. Future global warming will possibly accelerate the overlapping of the distributions of P. quercivorus and Q. crispula with the result that oak dieback in Q. crispula will become more prevalent in Japan.


[Outcomes after Gastrojejunostomy for Unresectable Gastric Cancer(Including Two Cases of Conversion Surgery) - A Retrospective Study].
Gastrojejunostomy as palliative surgery has been thought to contribute towards resumption of food intake and improvement of the patient's quality of life. This study aimed to examine the effect of gastrojejunostomy for unresectable gastric cancer on mortality and postoperative course. We retrospectively examined the records of 34 patients who underwent gastrojejunostomy for unresectable gastric cancer in our hospital from April 2008 to November 2015. Characteristics of the patients and operations, postoperative courses, and overall survival were assessed. The Kaplan-Meier method and loglank test were used for the survival analysis. The median overall survival was 310 days(95%CI: 136-485), and 1 year overall survival rate was 45%(95%CI: 27.5-61.1)in 34 patients who underwent gastrojejunostomy. Liver metastasis was associated with a lower survival rate, and chemotherapy after gastrojejunostomy was associated with a significantly higher survival rate. Two of 34 patients(5.9%)underwent conversion surgery after effective chemotherapy. Gastrojejunostomy for unresectable gastric cancer may have the potential to contribute towards not only an improvement in the patient's quality of life with regard to the resumption of food intake, but also prolongation of the overall survival with chemotherapy and conversion surgery.


Neuroenhancement among German university students: motives, expectations, and relationship with psychoactive lifestyle drugs.
Recent research has indicated that neuroenhancement (NE), the use of legal or illegal drugs by healthy individuals to improve their cognitive performance, is widely practiced among students in both the United States and Germany. The primary objective of this study was to identify the motives for and beliefs regarding the benefits and risks of practicing NE among a sample of German university students and graduates. The secondary objective was to determine the relationship between the use of neuroenhancers and the use of several common psychoactive lifestyle drugs. A web-based survey was used to interview students and postgraduates. Of the 1,324 participants, 93 reported having practiced NE for the primary motives of improving concentration (55%) and increasing vigilance (49%). Participants who reported having practiced NE were more likely to assess NE as more beneficial and less harmful compared to participants who reported not having practiced NE. The former also reported greater use of all lifestyle drugs except alcohol compared to the latter. The primary motives for practicing NE are associated with management of a high level of stress and a large academic workload. As such, decreasing the prevalence of NE among students requires implementation of strategies targeting stress reduction and workload management.


Direct amide synthesis from either alcohols or aldehydes with amines: activity of Ru(II) hydride and Ru(0) complexes.
An in situ generated catalyst from readily available RuH(2)(PPh(3))(4), an N-heterocyclic carbene (NHC) precursor, NaH, and acetonitrile was developed. The catalyst showed high activity for the amide synthesis directly from either alcohols or aldehydes with amines. When a mixture of an alcohol and an aldehyde was reacted with an amine, both of the corresponding amides were obtained with good yields. Homogeneous Ru(0) complexes such as (eta(4)-1,5-cyclooctadiene)(eta(6)-1,3,5-cyclooctatriene)ruthenium [Ru(cod)(cot)] and Ru(3)(CO)(12) were also active in the amidation of an alcohol or an aldehyde with the help of an in situ generated NHC ligand.


Superinfected and Ruptured Occipital Meningocele: Case Report.
Meningocele is a rare congenital malformation of the central nervous system resulting from a herniation of the meninges containing cerebrospinal fluid through a bony defect in the skull. It is part of neural tube closure anomalies. The overall incidence of meningocele is 0.8 to 3 per 10 000 live births; it varies based on geographical location and race, with a predominance of occipital localization. Among diagnostic methods, computed tomography (CT) and magnetic resonance imaging (MRI) remain crucial examinations. Prenatal diagnosis of this malformation primarily relies on ultrasound and screening through maternal serum alpha-fetoprotein (AFP) levels. They typically manifest very early at birth with a highly suggestive radioclinical presentation. Surgical treatment usually allows for a definitive cure. Superinfection and rupture of the meningocele are exceptional, resulting from delayed diagnosis and management. In several developed countries, prevention through genetic counseling and the intake of folic acid during the periconceptional period, along with accurate prenatal diagnosis and the legalization of therapeutic abortion, has led to a decrease in the prevalence of meningoceles. In less developed countries, where there is a delay in diagnosis in exceptional cases, superinfection and rupture may occur. We present the case of an 8-month-old infant with a complicated occipital meningocele with superinfection and rupture.


Epidemiology and early identification of autism: research challenges and opportunities.
Recent studies suggest that the prevalence of autism spectrum disorders may be as high as 60 per 10000, considerably greater than the long-accepted figure of 5 per 10 000 for classic autism. Increased recognition, the broadening of the diagnostic concept and methodological differences across studies may account for most or all of the apparent increase in prevalence, although this cannot be quantified. In addition to the implications for families and services, these conceptual changes will affect the scientific study of autism. At present, case definition is reliant on the behavioural and developmental picture alone. Because the behavioural phenotype of autism and the broader autism spectrum disorders includes individuals with different ultimate aetiologies, even when biological or genetic markers are found they will not be present in all individuals with the phenotype. The fact that autism is not a unitary 'disorder' presents a significant challenge to genetic, biological, neurological and psychological research. Progress has recently been made in the earlier identification of autism both through screening programmes and by increased understanding and enhanced surveillance. This offers an opportunity to better understand the early developmental course of autism and may provide additional clues to the underlying pathology.


Metal Bioaccumulation by Estuarine Food Webs in New England, USA.
Evaluating the degree of metal exposure and bioaccumulation in estuarine organisms is important for understanding the fate of metals in estuarine food webs. We investigated the bioaccumulation of Hg, methylmercury (MeHg), Cd, Se, Pb, and As in common intertidal organisms across a watershed urbanization gradient of coastal marsh sites in New England to relate metal exposure and bioaccumulation in fauna to both chemical and ecological factors. In sediments, we measured metal and metalloid concentrations, total organic carbon (TOC) and SEM-AVS (Simultaneously extracted metal-acid volatile sulfides). In five different functional feeding groups of biota, we measured metal concentrations and delta 15N and delta 13C signatures. Concentrations of Hg and Se in biota for all sites were always greater than sediment concentrations whereas Pb in biota was always lower. There were positive relationships between biota Hg concentrations and sediment concentrations, and between biota MeHg concentrations and both pelagic feeding mode and trophic level. Bioavailability of all metals measured as SEM-AVS or Benthic-Sediment Accumulation Factor was lower in more contaminated sites, likely due to biogeochemical factors related to higher levels of sulfides and organic carbon in the sediments. Our study demonstrates that for most metals and metalloids, bioaccumulation is metal specific and not directly related to sediment concentrations or measures of bioavailability such as AVS-SEM.


Evidence-based process for decision-making in the analysis of legal demands for medicines in Brazil.
Legal actions have been playing a significant role as an alternative pathway to access to medicines in Brazil. These lawsuits demand medicines used in Primary Health Care as well as medicines that are still in clinical research and have not been market approved by the Brazilian National Agency for Sanitary Surveillance (ANVISA). The goal was to analyze medicines demanded through lawsuits brought to the judicial district which includes the city of Rio de Janeiro, Brazil, from July/2007 to June/2008. The medicines in 281 lawsuits were examined for their respective indications, classified according to their presence in publicly-funded lists, market approval by ANVISA, compliance with national clinical guidelines, existence of alternative therapies in lists and support of indication by scientific evidence. Six different categories were described, which are deemed useful to managers and the Judiciary in decision-making. The support of evidence is of utmost importance for medicines that are not included in public funding lists and also for those with no available therapeutic alternatives.


Differences in Healthcare Expenditures, Visits, and Prescriptions by Race for Common Benign Urologic Conditions.
To identify differences in healthcare expenditures and utilization by race in patients treated for common benign urologic conditions. A retrospective secondary data analysis was conducted of patients with common benign urologic conditions using 2016-2018 Medical Expenditure Panel Survey data. Benign conditions included urolithiasis, cystitis, erectile dysfunction (ED), pelvic organ prolapse (POP), urinary incontinence (UI), and benign prostatic hyperplasia (BPH). Generalized linear models were used to evaluate the relationship between total healthcare expenditures and utilization and race for each condition. Adjusted analyses accounted for age, sex, number of chronic conditions, poverty status, self-reported health status, marital status, highest degree of educational attainment, and insurance status. The weighted analysis sample consisted of 27,110,416 patients, of whom 80.9% were Non-Hispanic white, 6.9% Non-Hispanic black, and 12.2% other minority races. After adjustment, total healthcare expenditures were significantly lower for Non-Hispanic blacks (incidence rate ratio [IRR] = 0.19, 95% confidence interval [CI]: 0.06-0.61) and other minority races (IRR = 0.30, 95% CI: 0.10-0.88) compared to Non-Hispanic whites treated for ED. Similarly, compared to Non-Hispanic whites, healthcare expenditures were significantly lower for Non-Hispanic blacks treated for UI (IRR = 0.56, 95% CI: 0.35-0.90). Healthcare expenditures are significantly lower for Non-Hispanic black patients treated for ED and UI in the US Future research is needed to determine if these differences represent an inequality in the delivery of urologic care for patients with these conditions.


Enterococcal endocarditis presenting as an isolated aortic valve aneurysm: case report and review of literature.
A 53-year-old man who presented with an embolic stroke was found to have new mild to moderate aortic valve regurgitation on transthoracic echocardiography. Subsequent transesophageal echocardiography revealed an isolated aortic valve aneurysm, without evidence of valve vegetations. Four of 4 blood cultures grew Enterococcus faecalis. This unique case represents the first report of an aortic valve aneurysm associated with enterococcal endocarditis. An important teaching point is the need to investigate for endocarditis in patients with valve aneurysms of unknown etiology, even in the absence of valve vegetations on transesophageal echocardiography.


Cyclic changes in the vaginal epithelium of normal rhesus macaques.
Studies in nonhuman primates indicate that changes in the thickness and integrity of the vaginal epithelium affect the transmission rates of HIV-1, but few studies have examined the normal variations that may occur in the vagina of normal macaques as a result of aging or changes in the menstrual cycle. This study was conducted to determine if differences occur in the thickness of the vaginal mucosa with age or menses. Vaginal mucosal thickness was compared in 46 rhesus macaques grouped as juvenile (1-3 years old), mature cycling (3-21 years old), and geriatric (> 21 years old). Epithelia of mature cycling macaques were also compared at different stages of the menstrual cycle. Older females (> 21 years) had the thinnest and least keratinized epithelium of all groups, followed by the youngest females (< 3 years). The vaginal epithelium was also thinner in cycling macaques during menses compared to the follicular stage. In addition, young, geriatric, or cycling macaques during menses had minimal keratinization. We hypothesize that normal physiologic changes in the vaginal epithelium of women occur with age and menses, which may affect a woman's susceptibility to HIV-1 transmission and other sexually transmitted diseases. Also, age and menstrual cycle should be considered when designing vaginal transmission experiments in rhesus macaques.


Changes in mouse corneal epithelial innervation with age.
We defined the quantitative changes in corneal epithelial nerve fibers during mouse development. Corneal whole mounts from 36 mice were immunostained with a specific anti-β-III tubulin antibody to label nerve fibers. Epithelial nerve fibers in the whole cornea were scanned and imaged using deconvolution microscopy. Subbasal nerve fiber and nerve terminal densities were calculated based on the length of nerve fibers located in each 1 mm² area of the corneal surface. The epithelial nerve terminals and corneal surface areas increased at different rates; therefore, the variations in corneal epithelial nerve terminal density and number were asynchronous. The maximum epithelial nerve terminal density was reached at postnatal day 24, which remained constant until postnatal month 2 and then decreased significantly. However, the epithelial nerve terminal number increased significantly until postnatal month 2 and then subsequently decreased significantly. In contrast to the epithelial nerve terminal, the subbasal nerve fiber density and number increased significantly until postnatal month 2 and then decreased. Since the subbasal nerve vortex was formed at postnatal day 24, its location, morphological appearance, and directionality did not display any further changes with age. The changes in the corneal epithelial nerve fibers can be divided into two stages after birth (day 1 to 2 months and 2-15 months). During the first stage, the corneal epithelial nerve fiber density increased significantly with increasing corneal surface area. During the second stage, the density presented a significant downward trend.


Phase II study of carboxyamidotriazole in patients with advanced renal cell carcinoma refractory to immunotherapy: E4896, an Eastern Cooperative Oncology Group Study.
The current study evaluated the response rate and 6-month time to disease progression of the antiangiogenesis agent carboxyamidotriazole (CAI) in patients with metastatic renal cell carcinoma (RCC). Fifty-seven patients with histologically confirmed metastatic RCC that progressed after biologic therapy (interferon or interleukin-2) were enrolled. Four patients were ineligible. CAI was administered orally as a 28-day cycle. Response and time to disease progression were evaluated. Fifteen of 53 eligible patients received > 5 cycles, but 13 patients eventually discontinued treatment because of progressive disease. The majority of toxicities were Grade 1. However, Grade 3/4 toxicities did occur, the majority of which were gastrointestinal in nature. One of 47 patients evaluable achieved a partial response (1.9%) lasting 172 days. Six of 53 patients were alive and disease progression free at 6 months from the start of treatment (11.3%). The median overall survival was 12.5 months. The survival periods in the low-risk, intermediate-risk, and poor-risk groups were 16.2 months, 20.9 months, and 5.8 months, respectively. Patients in trials of second-line therapy appear to have a better prognosis than previously considered, in part because they are eligible for another clinical trial. CAI was found to have little to no effect on the natural history of progressive RCC.


Systematic review of level 1 evidence for laparoscopic pediatric surgery: do our procedures comply with the requirements of evidence-based medicine?
Laparoscopic techniques have evolved quickly in recent years and are regarded as standard procedures in pediatric surgery today. However, most studies comparing laparoscopic operations with the corresponding open procedure do not reach a high level of evidence according to the criteria of the Oxford Centre for Evidence-Based Medicine. For evidence Level 1a, a meta-analysis (MA) of different randomized controlled trials (RCTs) is required. For evidence Level 1b, at least one RCT is required. The aim of our study was to evaluate the availability of Level 1 studies comparing laparoscopic procedures with the corresponding open operation in pediatric surgery. Systematic review of clinical Level 1 studies using PubMed. All MA and RCT were identified and individually reviewed. Only studies comparing pediatric laparoscopic procedures with the corresponding open operation were included. RCTs included in MA were only individually analyzed if they focused on additional endpoints. Endpoints of the study were advantages and disadvantages of laparoscopy compared with the open operation. A total of 20 manuscripts met the inclusion criteria (9 MA and 11 RCT). Studies providing evidence Level 1a were identified for five types of laparoscopic procedures (laparoscopic appendectomy, inguinal hernia repair, orchidopexy, pyloromyotomy, and varicocelectomy). Studies providing evidence Level 1b were identified for two types of laparoscopic procedures (fundoplication and pyeloplasty). The advantages of laparoscopy were less wound infections, ileus and postoperative pain (appendectomy), less retching (fundoplication), lower incidence of metachronous inguinal hernia, shorter hospital stay (appendectomy, orchiopexy, and pyeloplasty), and shorter time to full feeds (pyloromyotomy). Studies providing evidence Level 1 are only available for seven laparoscopic procedures in pediatric surgery. Effort has to be made to extend the existing Level 1 evidence and to gain high level evidence for further laparoscopic procedures.


Toxicological and cytophysiological aspects of lanthanides action.
Lanthanides, also called rare-earth elements, are an interesting group of 15 chemically active, mainly trivalent, f-electronic, silvery-white metals. In fact, lanthanides are not as rare as the name implies, except for promethium, a radioactive artificial element not found in nature. The mean concentrations of lanthanides in the earth's crust are comparable to those of life-important elements like iodine, cobalt and selenium. Many lanthanide compounds show particular magnetic, catalytic and optic properties, and that is why their technical applications are so extensive. Numerous industrial sources enable lanthanides to penetrate into the human body and therefore detailed toxicological studies of these metals are necessary. In the liver, gadolinium selectively inhibits secretion by Kupffer cells and it decreases cytochrome P450 activity in hepatocytes, thereby protecting liver cells against toxic products of xenobiotic biotransformation. Praseodymium ion (Pr3+) produces the same protective effect in liver tissue cultures. Cytophysiological effects of lanthanides appear to result from the similarity of their cationic radii to the size of Ca2+ ions. Trivalent lanthanide ions, especially La3+ and Gd3+, block different calcium channels in human and animal cells. Lanthanides can affect numerous enzymes: Dy3+ and La3+ block Ca2+-ATPase and Mg2+-ATPase, while Eu3+ and Tb3+ inhibit calcineurin. In neurons, lanthanide ions regulate the transport and release of synaptic transmitters and block some membrane receptors, e.g. GABA and glutamate receptors. It is likely that lanthanides significantly and uniquely affect biochemical pathways, thus altering physiological processes in the tissues of humans and animals.


Region-Level Functional and Effective Network Analysis of Human Brain During Cognitive Task Engagement.
Mental disorders are a major source of disability, with few effective treatments. It has recently been argued that these diseases might be effectively treated by focusing on decision-making, and specifically remediating decision-making deficits that act as "ingredients" in these disorders. Prior work showed that direct electrical brain stimulation can enhance human cognitive control, and consequently decision-making. This raises a challenge of detecting cognitive control lapses directly from electrical brain activity. Here, we demonstrate approaches to overcome that challenge. We propose a novel method, referred to as maximal variance node merging (MVNM), that merges nodes within a brain region to construct informative inter-region brain networks. We employ this method to estimate functional (correlational) and effective (causal) networks using local field potentials (LFP) during a cognitive behavioral task. The effective networks computed using convergent cross mapping differentiate task engagement from background neural activity with 85% median classification accuracy. We also derive task engagement networks (TENs): networks that constitute the most discriminative inter-region connections. Subsequent graph analysis illustrates the crucial role of the dorsolateral prefrontal cortex (dlPFC) in task engagement, consistent with a widely accepted model for cognition. We also show that task engagement is linked to prefrontal cortex theta (4-8 Hz) oscillations. We, therefore, identify objective biomarkers associated with task engagement. These approaches may generalize to other cognitive functions, forming the basis of a network-based approach to detecting and rectifying decision deficits.


Transoesophageal echocardiography during coronary artery bypass procedures: impact on surgical planning.
Intraoperative transesophageal echocardiography (iTEE) is widely accepted and routinely used during heart valve surgery. However, the impact of iTEE among patients undergoing coronary artery bypass grafting (CABG) is less well documented. In this study, we aim to define the impact of iTEE in patients undergoing myocardial revascularization for severe coronary artery disease. We analyzed clinical data and preoperative and intraoperative echocardiograms of all adults who underwent on pump coronary bypass and iTEE between January 2008 and December 2008. 521 patients (mean age 69±14 years) were studied. New prebypass findings were obtained in 82 (15.7%) patients: in 62 (11.9%) of these patients, this information changed the surgical plan. New postbypass findings were obtained in 8 patients (1.5%) and the surgical plan was altered in 4 patients (0.7%). Overall new findings were obtained in 90 patients (17.2%) and the surgical plan was altered in 66 patients (12.6%). These data support the routine use of iTEE among patients undergoing surgical myocardial revascularization.


Management of Male Infertility with Coexisting Sexual Dysfunction: A Consensus Statement and Clinical Recommendations from the Asia-Pacific Society of Sexual Medicine (APSSM) and the Asian Society of Men's Health and Aging (ASMHA).
Male infertility (MI) and male sexual dysfunction (MSD) can often coexist together due to various interplay factors such as psychosexual, sociocultural and relationship dynamics. The presence of each form of MSD can adversely impact male reproduction and treatment strategies will need to be individualized based on patients' factors, local expertise, and geographical socioeconomic status. The Asia Pacific Society of Sexual Medicine (APSSM) and the Asian Society of Men's Health and Aging (ASMHA) aim to provide a consensus statement and practical set of clinical recommendations based on current evidence to guide clinicians in the management of MI and MSD within the Asia-Pacific (AP) region. A comprehensive, narrative review of the literature was performed to identify the various forms of MSD and their association with MI. MEDLINE and EMBASE databases were searched for the following English language articles under the following terms: "low libido", "erectile dysfunction", "ejaculatory dysfunction", "premature ejaculation", "retrograde ejaculation", "delayed ejaculation", "anejaculation", and "orgasmic dysfunction" between January 2001 to June 2022 with emphasis on published guidelines endorsed by various organizations. This APSSM consensus committee panel evaluated and provided evidence-based recommendations on MI and clinically relevant MSD areas using a modified Delphi method by the panel and specific emphasis on locoregional socio-economic-cultural issues relevant to the AP region. While variations exist in treatment strategies for managing MI and MSD due to geographical expertise, locoregional resources, and sociocultural factors, the panel agreed that comprehensive fertility evaluation with a multidisciplinary management approach to each MSD domain is recommended. It is important to address individual MI issues with an emphasis on improving spermatogenesis and facilitating reproductive avenues while at the same time, managing various MSD conditions with evidence-based treatments. All therapeutic options should be discussed and implemented based on the patient's individual needs, beliefs and preferences while incorporating locoregional expertise and available resources.


Molecular variability of house finch Mycoplasma gallisepticum isolates as revealed by sequencing and restriction fragment length polymorphism analysis of the pvpA gene.
Mycoplasma gallisepticum, a major pathogen of chickens and turkeys, has caused significant declines in house finch (Carpodacus mexicanus) populations in the eastern United States since it was first observed in this species in 1994. There is evidence that M. gallisepticum infection is now endemic among eastern house finches, although disease prevalence has declined, suggesting an evolving host-parasite relationship. Studies based on randomly amplified polymorphic DNA (RAPD) have documented the presence of a single, unique RAPD profile in house finch M. gallisepticum isolates, suggesting a single point source of origin, which agrees with the known epidemiologic observations. In the present study, we evaluated the molecular variability of 55 house finch isolates as well as 11 chicken and turkey isolates including reference strains of M. gallisepticum. Molecular variability was evaluated by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis and nucleotide sequencing of the pvpA gene, which encodes for the putative cytadhesin protein PvpA. Three different RFLP groups and 16 genotypes were evident from the 55 house finch isolates evaluated. Sequence analysis of pvpA gene PCR products showed that although most house finch M. gallisepticum isolates clustered more closely to each other, others clustered more closely to either turkey or chicken field isolates. These findings suggest that house finch isolates are more polymorphic than previously recognized by RAPD studies. This feature may allow us to learn more about the molecular evolution and epidemiology of this emerging disease host-parasite relationship.


Assessment of coastal pollution through bioassay and transplantation of intertidal clams.
In the present study, a survey of Mahim creek and Bay area was undertaken that indicated absence of fauna, particularly molluscs from the area, which was a repository in the past. During bioassay experiments of Mahim creek water, the clams G. divaricatum and C. antiquata could not open their valves in 100% creek water and died within 12 hrs of exposure. The 96 hrs LC50 values of Mahim creek water for G. divaricatum and C. antiquata were found to be 20% and 40% respectively during summer and 38% and 57% respectively during rainy season. When two sets of the clams were transplanted at Mahim creek, they died within 12 hrs. These experiments suggest the extreme level of pollution in the area. This level of pollution is responsible for transforming the area into barren locality in terms of fauna, specially the rich molluscan diversity. However, Gorai creek was found to be comparatively very less polluted and it still serves as breeding and nursery ground for various fishes and prawn species. Hence it must be protected and conserved.


South African paediatric food-based dietary guidelines.
South African efforts to address both under- and overnutrition , and other nutrition-related public health issues, utilizing food-based dietary guidelines (FBDGs) as an educational tool, are introduced. However, the focus is placed on the development of paediatric FBDGs for infants and young children, from birth up to the age of 7 years, and how these were made compatible with scientific and local public health evidence on the one hand, and existing South African FBDGs for children over the age of 7 years, adolescents and adults, on the other. Members of the Working Group and other stakeholders are gratefully acknowledged.


Effects of central sympathetic inhibition on heart rate variability during steady-state exercise in healthy humans.
The profound reduction in heart rate variability (HRV) that occurs during exercise is thought to be, at least in part, the result of sympathetic nervous system activation. Moxonidine is a centrally acting anti-sympathetic drug, which suppresses sympathetic nervous system outflow by stimulation of central imidazoline receptors located in the rostral ventro-lateral medulla. This study was designed to investigate the combined effects of central sympathetic inhibition with moxonidine and steady-dynamic exercise on HRV. Ten normal males participated in a double-blind cross-over study, taking either placebo or 0.4 mg of moxonidine. The subjects were studied at rest and during steady-state exercise. HRV was measured considering both time and frequency domain parameters. As a non-linear measure, the Poincaré scatter-plot was measured and analysed quantitatively. Ventilation and gas exchange were also measured during exercise. In addition, plasma catecholamines were measured at rest and during exercise. The only parameter changed, at rest, by moxonidine was the blood pressure which was reduced. During exercise, moxonidine reduced plasma noradrenaline (NA), compared with the placebo (P<0.01). The only change observed in HRV during exercise was a significant reduction of the continuous long-term standard deviation (SD2) of the Poincaré scatter-plot of the R-R interval (P<0.05). However, the potential and prognostic significance of this result needs to be further assessed.


Localization and characterization of X chromosome inversion breakpoints separating Drosophila mojavensis and Drosophila arizonae.
Ectopic exchange between transposable elements or other repetitive sequences along a chromosome can produce chromosomal inversions. As a result, genome sequence studies typically find sequence similarity between corresponding inversion breakpoint regions. Here, we identify and investigate the breakpoint regions of the X chromosome inversion distinguishing Drosophila mojavensis and Drosophila arizonae. We localize one inversion breakpoint to 13.7 kb and localize the other to a 1-Mb interval. Using this localization and assuming microsynteny between Drosophila melanogaster and D. arizonae, we pinpoint likely positions of the inversion breakpoints to windows of less than 3000 bp. These breakpoints define the size of the inversion to approximately 11 Mb. However, in contrast to many other studies, we fail to find significant sequence similarity between the 2 breakpoint regions. The localization of these inversion breakpoints will facilitate future genetic and molecular evolutionary studies in this species group, an emerging model system for ecological genetics.


OCT angiography documented reperfusion of translocated autologous full thickness RPE-choroid graft for complicated neovascular age-related macular degeneration.
PurposeThe purpose of this study is to investigate the reperfusion of translocated retinal pigment epithelium (RPE)-choroid graft in the treatment of patients with neovascular age-related macular degeneration (nAMD), using OCT angiography (OCTA), a novel non-invasive, high-resolution imaging modality.Patients and methodsEighteen eyes of 18 consecutive patients suffering from complicated nAMD underwent RPE-choroid patch graft translocation surgery using a peripheral retinotomy and flap-over technique. We analyzed functional and anatomical outcome using visual acuity, Spectral Domain OCT and OCTA.ResultsWith a mean follow-up of 11 months, out of 18 patients, 15 gained vision, 1 remained stable, and 2 lost vision. Overall, the visual acuity improved with a mean of 30 letters. Perfusion of the graft tissue was confirmed in all patients. Two patients developed signs of a recurrent neovascular membrane during follow-up. No cases of proliferative vitreoretinopathy occurred in this series.ConclusionsOCTA images show signs of perfusion in all grafts. Encouraging functional results and low risk of severe complications suggest that RPE-choroid graft translocation is a valid option in patients with complicated nAMD.


Palladium-Catalyzed Cross-Coupling of N-Sulfonylaziridines and Alkenylboronic Acids: Stereospecific Synthesis of Homoallylic Amines with Di- and Trisubstituted Alkenes.
A palladium-catalyzed cross-coupling of 2-alkylaziridines with alkenylboronic acids to give homoallylamines is presented. The reaction is highly regioselective and stereospecific and provides convenient access to enantioenriched amines with 1,1-disubstituted, 1,2-disubstituted, and trisubstituted alkenes. The modular synthesis of a 2,5-disubstituted pyrrolidine natural product was completed in three steps and 67% overall yield.


Testing for additivity at select mixture groups of interest based on statistical equivalence testing methods.
Several assumptions, defined and undefined, are used in the toxicity assessment of chemical mixtures. In scientific practice mixture components in the low-dose region, particularly subthreshold doses, are often assumed to behave additively (i.e., zero interaction) based on heuristic arguments. This assumption has important implications in the practice of risk assessment, but has not been experimentally tested. We have developed methodology to test for additivity in the sense of Berenbaum (Advances in Cancer Research, 1981), based on the statistical equivalence testing literature where the null hypothesis of interaction is rejected for the alternative hypothesis of additivity when data support the claim. The implication of this approach is that conclusions of additivity are made with a false positive rate controlled by the experimenter. The claim of additivity is based on prespecified additivity margins, which are chosen using expert biological judgment such that small deviations from additivity, which are not considered to be biologically important, are not statistically significant. This approach is in contrast to the usual hypothesis-testing framework that assumes additivity in the null hypothesis and rejects when there is significant evidence of interaction. In this scenario, failure to reject may be due to lack of statistical power making the claim of additivity problematic. The proposed method is illustrated in a mixture of five organophosphorus pesticides that were experimentally evaluated alone and at relevant mixing ratios. Motor activity was assessed in adult male rats following acute exposure. Four low-dose mixture groups were evaluated. Evidence of additivity is found in three of the four low-dose mixture groups. The proposed method tests for additivity of the whole mixture and does not take into account subset interactions (e.g., synergistic, antagonistic) that may have occurred and cancelled each other out.


Physiological models of body composition and human obesity.
The body mass index (BMI) is the standard parameter for predicting body fat fraction and for classifying degrees of obesity. Currently available regression equations between BMI and fat are based on 2 or 3 parameter empirical fits and have not been validated for highly obese subjects. We attempt to develop regression relations that are based on realistic models of body composition changes in obesity. These models, if valid, can then be extrapolated to the high fat fraction of the morbidly obese. The analysis was applied to 3 compartment (density and total body water) measurements of body fat. The data was collected at the New York Obesity Research Center, Body Composition Unit, as part of ongoing studies. A total of 1356 subjects were included, with a BMI range of 17 to 50 for males and 17 to 65 for females. The body composition model assumes that obese subjects can be represented by the sum of a standard lean reference subject plus an extra weight that has a constant adipose, bone and muscle fraction. There is marked age and sex dependence in the relationship between BMI and fat fraction. There was no significant difference among Caucasians, Blacks and Hispanics while Asians had significantly greater fat fraction for the same BMI. A linear relationship between BMI and fat fraction provides a good description for men but overestimates the fat fraction in morbidly obese women for whom a non-linear regression should be used. New regression relations for predicting body fat just from experimental measurements of body density are described that are more accurate then those currently used. From the fits to the experimental BMI and density data, a quantitative description of the bone, adipose and muscle body composition of lean and obese subjects is derived. Physiologically realistic models of body composition provide both accurate regression relations and new insights about changes in body composition in obesity.


Pregnancy in patients with renal transplants in Malaysia.
There were 72 pregnancies in 46 renal transplants (RTs) between 1984 and 2001, 89% from living donors, 11% cadaveric. Mean age at RT was 26.9 +/- 4.3 years and at pregnancy 30.7 +/- 4.7 years. Mean time to pregnancy after RT was 4.5 +/- 3.1 years. 54% were unplanned. 45 (63%) resulted in surviving infants, 37% delivered by Caesarean section. 35% were premature. Mean birth weight was 2.38 +/- 0.57 kg. 64% were on cyclosporine. No patient had an acute rejection during pregnancy; 38% had pre-existing hypertension. Complications include urinary infection (13%), proteinuria (15%) and preeclampsia (15%). Mean serum creatinine before pregnancy was 112.7 +/- 32.6 umol/l, 1 year post-pregnancy it was 119.4 +/- 38.7. The mean time of follow up of mothers is 4.9 +/- 3.5 years. 10 year graft survival was 83% and patient survival 94%.


Category essence or essentially pragmatic? Creator's intention in naming and what's really what.
Daily experience is filled with objects that have been created by humans to serve specific purposes. For such objects, the very act of creation may be a key element of how people understand them. But exactly how does creator's intention matter? We evaluated its contribution to two forms of categorization: the name selected for an artifact, and intuitions about what an artifact "really" is. To contrast the possibility that intention serves as an essence (Bloom, P. (1996). Intention, history, and artifact concepts. Cognition, 60, 1-29; Bloom, P. (1998). Theories of artifact categorization. Cognition, 66, 87-93.) determining an artifact's name with the possibility that it matters through its relevance to discourse goals, participants in three experiments read scenarios about people interacting with an artifact and then judged the suitability of different names for it. The intention of the creator was of differing degrees of relevance to the communication, and the relevance of other aspects of the entity varied in a complementary fashion. We found that name selection was altered by the communicative goals of a situation, and name choice was most consistent with creator's intention when the situation made intention relevant to achieving those goals. In a fourth experiment, we used the same scenarios to test the possibility that intention serves as an essence determining intuitions about what an object "really" is. The impact of creator's intention was modulated by the discourse context. These findings suggest that creator's intention influences both name choice and intuitions about what something "really" is by virtue of its impact on how communicative goals are best realized.


Different Regulatory Strategies of Arsenite Oxidation by Two Isolated Thermus tengchongensis Strains From Hot Springs.
Arsenic is a ubiquitous constituent in geothermal fluids. Thermophiles represented by Thermus play vital roles in its transformation in geothermal fluids. In this study, two Thermus tengchongensis strains, named as 15Y and 15W, were isolated from arsenic-rich geothermal springs and found different arsenite oxidation behaviors with different oxidation strategies. Arsenite oxidation of both strains occurred at different growth stages, and two enzyme-catalyzed reaction kinetic models were observed. The arsenite oxidase of Thermus strain 15W performed better oxidation activity, exhibiting typical Michaelis-Menten kinetics. The kinetic parameter of arsenite oxidation in whole cell showed a V max of 18.48 μM min-1 and K M of 343 μM. Both of them possessed the arsenite oxidase-coding genes aioB and aioA. However, the expression of gene aioBA was constitutive in strain 15W, whereas it was induced by arsenite in strain 15Y. Furthermore, strain 15Y harbored an intact aio operon including the regulatory gene of the ArsR family, whereas a genetic inversion of an around 128-kbp fragment produced the inactivation of this regulator in strain 15W, leading to the constitutive expression of aioBA genes. This study provides a valuable insight into the adaption of thermophiles to extreme environments.


[BIOCOMPATIBILITY OF POROUS POLY LACTIC ACID/BONE MATRIX GELATIN COMPOSITE BIOMATERIALS FOR BONE REPAIR].
To evaluate the biocompatibility of poiy lactic acid/bone matrix gelatin (PLA/BMG) composite biomaterial so as to lay a foundation for bone defect repair. Rats' MC3T3-E1 cells were cultured with leaching solution of PIJA/BMG and PLA material respectively for 7 days. The cell proliferation rate was tested by MTT and cell toxicity grading was carried out everyday. The PLA/BMG and MG3T3-E1 cells were co-cultured, the cell shape and proliferation were observed by inverted phase contrast microscope at 1, 3, and 5 days and cell adhesion by scanning electron microscope at 5 days. The PLA and PLA/BMG were implanted subcutaneously ilS Wistar rats. The histological observation was done, and the thickness of fibrous membrane, the number of inflammatory cells, and the vascularization area were measured at postoperative 2nd, 4th, and 8th week. The tests for cytotoxicity in vitro showed that the cell proliferation rates were over 100% and the cell cytotoxic grades were grade 0 at 1-7 days in PLA/BMG group. While in PLA group, the cell proliferation rates were less than 100% and the cell cytotoxic grades were grade 1 at 2, 4, and 7 days. After co-culture of PLA/BMG and MC3T3-E1 cells, cells grew on the surface and in the pores of PLA! BMG, and the cellular morphology was triangle or polygon with abundant microvillus on the surface. After subcutaneous implantation, the rats survived to the end of experiment, and incision healed well. PLA was wrapped by connective tissue where there were a lot of lymphocytes and neutrophiic granulocytes. The cells and tissue grew slowly in PLA. The PLA! BMG materials were wrapped by utile connective tissue where there were a few inflammatory cells. The connective tissue growth was observed in the center of PLA/BMG. There was no significant difference in the thickness of fibrous membrane between 2 groups at each time point (P>0.05). The number of inflammatory cells of PLA/BMG group were significantly less than those in PLA group at 2, 4, and 8 weeks (P<0.05); the vascularization area was significantly larger than that in PLA group (P<0.05). PLA/BMG composite biomaterials prepared by super critical-CO2 technique are good in cell and tissue biocompatibilty.


Severity and criteria based prompting for treatment of depressed patients.
Primary care physicians (PCPs) often do not respond to prompts based upon criteria-based depression screens, perhaps because these prompts do not account for depression severity. We conducted this pilot study to determine the feasibility of prompting for both diagnostic criteria and severity and to assess whether depression would be more attended to with positive "dual prompts" than prompts based on either criteria or symptom severity alone. Immediately prior to a routine care appointment, 87 adults from three primary care practices completed the PRIME-MD Clinician Evaluation Guide Mood Module (PRIME-MD; assesses depression criteria) and the Brief Depression Rating (BDR; assesses depressive symptom severity), and their results were issued in a salient PCP prompt on the chart. Immediately afterwards, patients reported the impact of the screening results upon treatment decisions during the encounter. Data were analyzed by X2, analysis of variance, and binomial regression. Compared to subjects screening positive on either depression criteria or severity alone (n = 10), those patients on both (n = 17) were more likely to report discussing depression, and agreement that the physician and patient decided treatment was needed and initiated or continued. There were no differences in patient satisfaction based on screening results. After accounting for PRIME-MD results, BDR scores predicted agreement with the physician and patient decided treatment was needed (OR = 22.03; 95% CI: 2.05-236.46). Supplementary severity-based depression screening is feasible, and might overcome the limitations of criteria-based screening alone. Future research could test this hypothesis in a large randomized trial.


Age differences in selective memory of goal-relevant stimuli under threat.
When faced with threat, people often selectively focus on and remember the most pertinent information while simultaneously ignoring any irrelevant information. Filtering distractors under arousal requires inhibitory mechanisms, which take time to recruit and often decline in older age. Despite the adaptive nature of this ability, relatively little research has examined how both threat and time spent preparing these inhibitory mechanisms affect selective memory for goal-relevant information across the life span. In this study, 32 younger and 31 older adults were asked to encode task-relevant scenes, while ignoring transparent task-irrelevant objects superimposed onto them. Threat levels were increased on some trials by threatening participants with monetary deductions if they later forgot scenes that followed threat cues. We also varied the time between threat induction and a to-be-encoded scene (i.e., 2 s, 4 s, 6 s) to determine whether both threat and timing effects on memory selectivity differ by age. We found that age differences in memory selectivity only emerged after participants spent a long time (i.e., 6 s) preparing for selective encoding. Critically, this time-dependent age difference occurred under threatening, but not neutral, conditions. Under threat, longer preparation time led to enhanced memory for task-relevant scenes and greater memory suppression of task-irrelevant objects in younger adults. In contrast, increased preparation time after threat induction had no effect on older adults' scene memory and actually worsened memory suppression of task-irrelevant objects. These findings suggest that increased time to prepare top-down encoding processes benefits younger, but not older, adults' selective memory for goal-relevant information under threat. (PsycINFO Database Record


A phase II pilot study to evaluate use of intravenous lidocaine for opioid-refractory pain in cancer patients.
Opioid-refractory pain is distressing because it is notoriously difficult to treat. Relief from adjuvant therapies often occurs after a lag time. Retrospective evidence points to a role for intravenous (IV) lidocaine in this setting for pain relief. This study was planned as a randomized, double-blind, placebo-controlled, crossover study in which eligible patients received both lidocaine and placebo infusions separated by two weeks. Primary endpoints were magnitude and duration of pain relief. Fifty patients were included in the study. Pain relief was significantly better (P<0.001) and more patients reported a decrease in analgesic requirements (P=0.0012) after lidocaine infusion than after placebo. Onset of analgesia was noted at a mean of 40+/-16.28 minutes after initiation of infusion of IV lidocaine. Mean duration of this analgesia, 9.34+/-2.58 days after the single infusion, was significantly longer than that for placebo (P<0.01). Side effects observed were tinnitus, perioral numbness, sedation, light-headedness, and headache. All side effects were self-limited and did not require any intervention except termination of lidocaine infusion in one case. These data demonstrate that a single IV infusion of lidocaine provided a significantly greater magnitude and duration of pain relief than placebo infusion in opioid-refractory patients with cancer pain. Side effects were tolerable. It is thus a promising modality worth investigating further to establish guidelines for its use in cancer patients with opioid-refractory pain.


Plazomicin for the treatment of patients with complicated urinary tract infection.
In June 2018, the United States Food and Drug Administration (FDA) approved plazomicin, a novel neoglycoside, for the treatment of adults with complicated urinary tract infections who have limited or no alternative treatment options. This approval was based on substantial preclinical and clinical work, and marks an important advance in the treatment of multidrug-resistant bacterial pathogens. This manuscript reviews the in vivo and in vitro work that led to the approval of plazomicin and examines how the drug may be used in the years ahead to treat patients with aggressive and life-threatening infections.


Total synthesis of iejimalide B. An application of the Shiina macrolactonization.
The potent anticancer compound iejimalide B (1) was prepared by a total synthesis through a strategy that features Julia olefinations, Wittig olefinations, a Carreira enantioselective alkynylation, a Heck reaction, a Marshall propargylation reaction, a Stille coupling, and a Shiina macrolactonization.


Role of Epstein-Barr Virus in the Development of Nasopharyngeal Carcinoma.
Southern China experiences larger extent of total cancer pathologies, of which nasopharyngeal carcinoma has the highest incidence under otorhinolaryngeal malignant carcinomas. Risk factor of nasopharyngeal carcinoma varies from hereditary causes to virus infection, among which Epstein-Barr virus (EBV) infection is the mostly investigated. The study into mechanism of EBV in occurrence, development and prognosis of nasopharyngeal carcinoma has been studied for several decades. The pathophysiology in making of EBV into a cancerogen includes proteins as latent membrane protein 1 (LMPs) and nucleic acids as micro-RNAs. In this paper, we reviewed till date studies focusing on relationship between EBV and nasopharyngeal carcinoma.


Endoluminal instrumentation is changing gastrointestinal surgery.
Advances in endoluminal instrumentation and technology are enabling endoscopists to perform increasingly sophisticated procedures. Indications for these procedures are likely to expand as outcomes studies show they are efficacious and cost-effective. This article highlights several recent advances in endoluminal suturing, dissecting, and ligating and discusses the impact of these advances on the practice of gastrointestinal surgery. Endoluminal suturing offers select patients with gastroesophageal reflux disease a safe and effective alternative to laparoscopic surgery. Devices designed for endoluminal hemostasis and endoscopic mucosal resection can be used effectively for a broader range of applications and are already being used to perform transluminal surgery in animal models; human trials are forthcoming. Gastrointestinal surgeons should support efforts to critically evaluate endoluminal techniques because they have an opportunity to improve care. Surgical residents planning careers in gastrointestinal surgery need to understand endoscopic techniques and consider their training opportunities.


Safety of aggressive statin therapy.
New cholesterol guidelines will lead to use of statins more frequently and at higher doses. Myopathy, the most common and potentially most serious adverse effect, is dose-related. Rhabdomyolysis, which is rare, appears to occur at a similar rate with all currently marketed statins. Since it can occur without warning symptoms, patients who take high doses or are at high risk for other reasons should be monitored more closely. The possibility that statins could increase the incidence of some kinds of cancer in humans, as they do in animals, is not supported by most of the data available to date, but longer followup is needed.


Left ventricular long axis tissue Doppler systolic velocity is independently related to heart rate and body size.
The physiological factors which affect left ventricular (LV) long-axis function are not fully defined. We investigated the relationships of resting heart rate and body size with the peak velocities and amplitudes of LV systolic and early diastolic long axis motion, and also with long-axis contraction duration. Two groups of adults free of cardiac disease underwent pulsed-wave tissue Doppler imaging at the septal and lateral mitral annular borders. Group 1 (n = 77) were healthy subjects <50 years of age and Group 2 (n = 65) were subjects between 40-80 years of age referred for stress echocardiography. Systolic excursion (SExc), duration (SDur) and peak velocity (s') and early diastolic excursion (EDExc) and peak velocity (e') were measured. SExc was not correlated with heart rate, height or body surface area (BSA) for either LV wall in either group, but SDur was inversely correlated with heart rate for both walls and both groups, and after adjustment for heart rate, males in both groups had a shorter septal SDur. Septal and lateral s` were independently and positively correlated with SExc, heart rate and height in both groups, independent of sex and age. There were no correlations of heart rate, height or BSA with either e` or EDExc for either wall in either group. Heart rate and height independently modify the relationship between s` and SExc, but neither are related to EDExc or e`. These findings suggest that s` and SExc cannot be used interchangeably for the assessment of LV long-axis contraction.


"Sequencing Matters": Investigating Suitable Action Sequences in Robot-Assisted Autism Therapy.
Social robots have been shown to be promising tools for delivering therapeutic tasks for children with Autism Spectrum Disorder (ASD). However, their efficacy is currently limited by a lack of flexibility of the robot's social behavior to successfully meet therapeutic and interaction goals. Robot-assisted interventions are often based on structured tasks where the robot sequentially guides the child towards the task goal. Motivated by a need for personalization to accommodate a diverse set of children profiles, this paper investigates the effect of different robot action sequences in structured socially interactive tasks targeting attention skills in children with different ASD profiles. Based on an autism diagnostic tool, we devised a robotic prompting scheme on a NAO humanoid robot, aimed at eliciting goal behaviors from the child, and integrated it in a novel interactive storytelling scenario involving screens. We programmed the robot to operate in three different modes: diagnostic-inspired (Assess), personalized therapy-inspired (Therapy), and random (Explore). Our exploratory study with 11 young children with ASD highlights the usefulness and limitations of each mode according to different possible interaction goals, and paves the way towards more complex methods for balancing short-term and long-term goals in personalized robot-assisted therapy.


Traumatized Refugees in Psychotherapy: Long-Term Changes in Personality, Mental Health, Well-Being, and Exile Life Functioning.
This pre- and posttreatment study of 22 severely traumatized adult refugees spanned a mean of 6.5 years. Changes in personality functioning, mental health, and well-being were examined using the Rorschach Performance Assessment System, Harvard Trauma Questionnaire, Hopkins Symptom Checklist-25, and the World Health Organization's Quality of Life-BREF questionnaire. A paired samples t-test revealed significant improvement after psychotherapy in traumatic ideation and initial severe disruptions in thought processes, reality testing, perception, self and other representations, and relational capacity (Cohen's d = 0.46-0.59). Symptoms of anxiety, depression, and posttraumatic stress were significantly reduced (d = 0.54-0.84), quality of life in the physical health and psychological health domains increased significantly (d = 0.87 and 0.97), and percentage of participants with exile language proficiency and work/study status increased significantly. The findings demonstrate the potential of psychotherapy to contribute to normalizing perceptual, cognitive, and relational capacities in severely traumatized refugees, paramount to well-being and functioning in exile.


Exploring changes in functional status while waiting for transcatheter aortic valve implantation.
Aortic stenosis (AS) is a structural heart disease primarily associated with ageing. For people with multiple co-morbidities, surgical treatment may not be a safe or feasible option. Transcatheter aortic valve implantation (TAVI) is indicated for patients with symptomatic AS who are at excessive risk for surgical valve replacement and are likely to derive significant benefit. Functional status can deteriorate during the time between referral and procedure because of the rapid disease progression of severe AS and varying wait-times for treatment in Canada. The purpose of this study was to examine changes in functional status between time of eligibility assessment and TAVI procedure date. An exploratory prospective cohort study was conducted to evaluate changes in functional status including gait speed, frailty scores and cognitive status. Thirty-two patients participated in the study with median age 81 years. Functional status declined between time of eligibility assessment and time of TAVI: gait speed increased by an average of 0.53 s (standard deviation (SD)=1.0, p=0.01) and frailty scores increased by an average of 0.31 (SD=0.64, p=0.01). Patients waiting longer than six weeks for TAVI had a larger decline in gait speed than patients waiting less than six weeks (p=0.02). Patients living alone had a larger increase in frailty scores compared to patients living with another adult (p=0.05). Older adults with life-limiting AS are vulnerable to changes in functional status. In the absence of TAVI wait-time benchmarks, findings may be used to facilitate individualized care and management strategies and inform health-care policy.


NIH conference. Cystinosis: progress in a prototypic disease.
To review the history, basic defect, pathogenesis, clinical manifestations, diagnosis, and treatment of nephropathic cystinosis. Lysosomal membrane transport studies, clinical reports, and a historically controlled 7-year trial of oral cysteamine therapy. University centers in the United States and Canada. One hundred forty-eight children, aged 0 to 12, with nephropathic cystinosis before renal transplant, who had renal tubular Fanconi syndrome, failure to grow, corneal cystine crystals, and elevated leukocyte cystine; 34 patients, aged 9 to 29, after transplant, some with visual impairment, corneal erosions, pancreatic dysfunction, or neurologic deterioration. Before transplant, replacement of renal losses, and treatment with oral cysteamine (55 mg/kg body weight.d for 1 to 6 years) and topical cysteamine eyedrops (0.1%, 1 drop/h while awake, for 6 months). After transplant, oral cysteamine and symptomatic treatment of late complications. Untreated patients reached renal failure at age 10. Oral cysteamine lowered leukocyte cystine over 80%, and in patients before transplant, improved growth and preserved renal function (mean creatinine clearance [+/- SE], 0.64 +/- 0.04 mL/s.1.73 m2 [38.5 +/- 2.5 mL/min.1.73 m2] in the cysteamine group compared with 0.50 +/- 0.03 mL/s.1.73 m2 [29.7 +/- 2.0 mL/min.1.73 m2] in controls; 95% CI for the difference, 1.8 to 15.8). Cysteamine eyedrops cleared the corneal crystals of two children less than 2 years old. Cystinosis is a lysosomal storage disease due to impaired transport of cystine out of lysosomes. In young children, growth can be improved and renal deterioration delayed or prevented by oral cysteamine. Nonrenal complications after transplant might be prevented with long-term oral cysteamine.


Electrocatalytic Reduction of NO3- to Ultrapure Ammonia on {200} Facet Dominant Cu Nanodendrites with High Conversion Faradaic Efficiency.
Nitrate (NO3-) reduction reaction (NtRR) is considered as a green alternative method for the conventional method of NH3 synthesis (Haber-Bosch process), which is known as a high energy consuming and large CO2 emitting process. Herein, the copper nanodendrites (Cu NDs) grown along with the {200} facet as an efficient NtRR catalyst have been successfully fabricated and investigated. It exhibited high Faradaic efficiency of 97% at low potential (-0.3 V vs RHE). Furthermore, the 15NO3- isotope labeling method was utilized to confirm the formation of NH3. Both experimental and theoretical studies showed that NtRR on the Cu metal nanostructure is a facet dependent process. Dissociation of NO bonding is supposed to be the rate-determining step as NtRR is a spontaneously reductive and protonation process for all the different facets of Cu. Density functional theory (DFT) calculations revealed that Cu{200} and Cu{220} offer lower activation energy for dissociation of NO compared to that of Cu{111}.


Cell-type-specific and regulated expression of a human gamma 1 heavy-chain immunoglobulin gene in transgenic mice.
A functionally rearranged human gamma 1 heavy-chain immunoglobulin gene was cloned from a human plasma cell leukemia cell line, ARH-77, into the phage lambda Charon 4A. The recombinant phage DNA was introduced into fertilized mouse eggs (about 200 copies of the human gene per egg). A total of 30 mice were born and were screened for the presence of the human gamma 1 gene by dot hybridization. Two of these 30 mice had integrated one or two copies of the gene. The gamma 1 mRNAs were detected only in spleen. Levels of gamma 1 mRNA and the percentage of spleen cells producing human gamma chain increased up to 50-fold after treatment with bacterial lipopolysaccharide (a B-cell mitogen) but not with concanavalin A (a T-cell mitogen), suggesting B-cell-specific and regulated expression of the human gamma 1 heavy-chain gene. Human gamma chain-producing cells were found only in the periphery of the germinal center of the white pulp in histological sections of the spleen but not in sections of other tissues. Human gamma chains appeared to be coupled with mouse light chains to form a complete IgG molecule and were secreted into the cell supernatant. The production and secretion of endogenous immunoglobulin heavy and light chains in transgenic mice appeared to be the same as in normal mice. About one-seventh of the spleen cells that produced endogenous mouse heavy chains also produced human gamma chains, but no cells that produced only human gamma chain were observed.


Bilaterally symmetrical ganglion and subchondral cysts of the knee: a case report.
A 49-year-old patient, with a maternal history of arthritis, presented with an extra-capsular lump of the left knee. Following magnetic resonance imaging (MRI) scan and excision biopsy, the lump proved to be a benign ganglion cyst. The scan had also shown focal subchondral cyst formation and articular cartilage wear in the medial femoral condyle and patella, with no other abnormality. Four years later, she presented with identical symptoms and signs in the right knee. MRI scan confirmed a symmetrical pattern of ganglion and subchondral cyst location and size. Although both ganglion and subchondral cysts of the knee are common, their development is poorly understood and this combination of cyst formation and chondral wear has not been previously documented. Symmetry of end-stage knee osteoarthritis (OA) is recognized by clinicians. We speculate that OA of the knee begins asymptomatically with point-specific loss of articular cartilage, typically reflecting an inherent and bilateral vulnerability to degeneration.


Mawson "tillite" in antarctica: preliminary report of a volcanic deposit of jurassic age.
Reexamination of the Mawson "Tillite" (Jurassic) of Antarctica indicates that the deposit is of volcanic origin and consists largely of both primary and reworked volcanic materials. No evidence diagnostic of a glacial origin was found.


[Marrow hypoplasia associated with congenital dyskeratosis. Case report].
Congenital dyskeratosis is a rare disease involving ectodermal derived tissues and presenting bone-marrow hypoplasia as a complication in one half of the cases. A 25 year-old male is presented who at age 12 showed retarded development with shortness of the 4th finger of his left hand, anomalous implantation of teeth, hyperpigmented skin and hyperkeratosis on his knees, hands and feet. He had anaemia (Hb 92 g/L) and leucopenia (2.7 x 10(9)/L) with neutropenia (0.34 x 10(9)/L) and his bone-marrow showed hypoplasia, especially affecting granulopoiesis. The cytogenetic studies were normal. No treatment was given, and a haematological re-evaluation performed 13 years later showed no significant quantitative changes. Decreased number of myeloid and megakaryocytic colonies were present in the bone-marrow cultures. The clinical and laboratory characteristics of the bone-marrow aplasia associated to congenital dyskeratosis are commented, stress being laid on its differentiation from other constitutional forms of aplasia, especially Fanconi's anaemia.


Multidrug therapy for leprosy: a game changer on the path to elimination.
Leprosy is present in more than 100 countries, where it remains a major cause of peripheral neuropathy and disability. Attempts to eliminate the disease have faced various obstacles, including characteristics of the causative bacillus Mycobacterium leprae: the long incubation period, limited knowledge about its mode of transmission, and its poor growth on culture media. Fortunately, the leprosy bacillus is sensitive to several antibiotics. The first antibiotic to be widely used for leprosy treatment was dapsone in the 1950s, which had to be taken over several years and was associated with increasing bacterial resistance. Therefore, in 1981, WHO recommended that all registered patients with leprosy should receive combination therapy with three antibiotics: rifampicin, clofazimine, and dapsone. Global implementation of this highly effective multidrug therapy took about 15 years. In 1985, 5·3 million patients were receiving multidrug therapy; by 1991, this figure had decreased to 3·1 million (a decrease of 42%) and, by 2000, to 597 232 (a decrease of almost 90%). This reduction in the number of patients registered for treatment was due to shortening of the treatment regimen and achievement of 100% coverage with multidrug therapy. This achievement, which owed much to WHO and the donors of the multidrug therapy components, prompted WHO in 1991 to set a global target of less than one case per 10 000 population by 2000 to eliminate the disease as a public health problem. All but 15 countries achieved this target. Since 2000, about 250 000 new cases of leprosy have been detected every year. We believe an all-out campaign by a global leprosy coalition is needed to bring that figure down to zero.


[The moderating effect analysis of mindfulness on perceived stress and job burnout of medical staff].
Objective: To explore the moderating mechanism of mindfulness on perceived stress and job burnout of medical staff. Methods: From November 2020 to March 2022, 1626 medical staff were investigated by questionnaires. Chinese Version Perceived Stress Scale (CPSS), Maslach Burnout Inventory-Human Service Survey (MBI-HSS) and Mindful Attention Awareness Scale (MAAS) were used to evaluate the perceived stress, three dimensions of job burnout[depersonalization (DP), emotional exhaustion (EE), personal accomplishment (PA) ], and mindfulness level of medical staff. The Spearman rank correlation analysis was used to analyze the correlation between mindfulness and perceived stress, job burnout of medical staff. And the SPSS PROCESS macro program was used to test the moderating effect of mindfulness on perceived stress and job burnout. Results: Among the 1626 medical staff, 57.38% had perceived stress with health risk (933/1626), and 63.84% (1038/1626) had job burnout, among them, with 618 (38.01%), 274 (16.85%), and 146 (8.98%) experiencing mild, moderate and severe job burnout, respectively. The scores of mindfulness among medical staff were significantly correlated with perceived stress and various dimensions of job burnout (EE, DP and PA) (r(s)=-0.155, -0.351, -0.315, 0.307, P<0.001). Mindfulness had a moderating effect between perceived stress and job burnout, which was achieved through three moderating pathways: perceived stress-mindfulness-EE, perceived stress-mindfulness-DP and perceived stress-mindfulness-PA (ΔR(2)=0.073, 0.06, 0.006, P<0.001) . Conclusion: Medical staff have a high level of job burnout, mindfulness plays a moderating role between perceived stress and job burnout. Specific measures can be taken to improve the level of mindfulness in medical staff, so as to prevent and alleviate job burnout of medical staff.


The Role of Primary Tumor Resection in Patients With Pancreatic Neuroendocrine Tumors With Liver Metastases.
Liver metastases (LMs) are common in advanced pancreatic neuroendocrine tumor (PNET) patients. Currently, the benefit of primary tumor resection (PTR) in the setting of PNET patients with liver metastases is still controversial in several guidelines. Data were extracted from the Surveillance, Epidemiology and End Results (SEER) database to evaluate this issue. The main index of interest in our study was overall survival time. Information on 536 PNET patients with liver metastases from the SEER database was identified. A total of 214 patients (PTR group) received primary tumor resection, and more than half of them (132 patients) had synchronous LM resection. The other 322 PNET patients (non-PTR group) with liver metastases did not receive primary tumor resection. A significant survival benefit was gained from PTR when compared with non-PTR patients, both in OS (72.93 ± 2.7 vs. 36.80 ± 2.22 months) and 3- or 5-year survival rates (75.1% vs. 28.9% and 67.9% vs. 22.3%, respectively). No difference was found between PTR alone and PTR with synchronous LM resection. From univariate and multivariate analyses, younger age (<65 years) and good or moderate tumor differentiation may be more important when considering primary tumor resection. However, we found that all grades of tumor differentiation could result in a better overall survival time after primary tumor resection. Our study suggested that primary tumor resection in pancreatic neuroendocrine patients with liver metastases could result in a longer survival time. Primary tumor resection with synchronous liver metastasis resection was not related to a better survival benefit. This treatment strategy may routinely be taken into consideration in these patients.


Chromosomal damage in two species of aquatic turtles (Emys orbicularis and Mauremys caspica) inhabiting contaminated sites in Azerbaijan.
The Caspian region and specifically the Apsheron peninsula of Azerbaijan are known to be polluted with a variety of environmental contaminants. These complex mixtures of contaminants make risk assessment difficult. We used the flow cytometry method (FCM) and the micronucleus assay (MN) to assess chromosomal damage in aquatic turtles (Emys orbicularis, the European pond turtle; and Mauremys caspica, the Caspian turtle) inhabiting contaminated wetlands in Azerbaijan. Evidence of genetic damage was found for two sites, Neftchala and Sumgayit, relative to a reference site, Ali Bairamly. Sediment samples from each site were analyzed for PAHs and mercury to evaluate potential contaminant associations with genetic damage. A significant positive correlation was documented between three-ring PAH sediment concentrations and FCM estimates of chromosomal damage in E. orbicularis. These data combine to show that the contaminated wetlands in Sumgayit and Neftchala are genotoxic and that three-ring PAHs are likely a significant influence on observed genotoxicity.


Exposure of phosphatidylethanolamine on the surface of apoptotic cells.
In the early stages of apoptosis, phosphatidylserine (PS) is translocated from the inner side of the plasma membrane to the outer layer, which allows phagocytes to recognize and engulf the apoptotic cells. In this study we have analyzed the cell surface exposure of phosphatidylethanolamine (PE) in apoptotic CTLL-2 cells, a cytotoxic T cell line, using a tetracyclic polypeptide of 19 amino acids (Ro09-0198) which specifically recognizes the structure of PE and forms a tight equimolar complex with the phospholipid. Fluorescence microscopic analysis showed that the peptide, conjugated with fluorescence-labeled streptavidin (FL-SA-Ro), bound effectively to the cell surface of cells undergoing apoptosis in response to withdrawal of interleukin-2 from the culture media, but not to nonapoptotic cells. The binding of FL-SA-Ro to apoptotic cells was not uniform and the intense staining was observed on surface blebs of apoptotic cells. The FL-SA-Ro binding was inhibited specifically by liposomes containing PE, suggesting that PE is mainly exposed on the surface blebs of apoptotic cells. The specific binding of FL-SA-Ro to the apoptotic cells was also confirmed using a flourescence-activated cell sorter and the time-dependent cell surface exposure of PE correlated well with the exposure of PS, as detected by the binding of annexin V. This study provides the first direct evidence that PE as well as PS is exposed on the cell surface during the early stages of apoptosis, resulting in the total loss of asymmetric distribution of aminophospholipids in the plasma membrane bilayer.


Needlestick and Sharp Instruments Injuries among Brazilian Dentistry Students.
The occurrence of occupational accidents is common among students and dentists. The present study is aimed to evaluate the prevalence and characteristics of needlestick and sharp instrument injuries among dentistry students. A documentary research was carried out with data being obtained from the analysis of 137 medical records of injuries caused by needlestick and sharp instruments occurring in the period from 2012 to 2016 and were analyzed regarding the characteristics of the victim (gender and age) and the accident (year, time, environment, and time interval between exposure and search for care). Data were organized in the Statistical Package for Social Sciences software version 18 and were presented through descriptive statistics. The occurrence of accidents was high (43.1%), with the predominance of female victims (66.1%) and aged up to 23 years (55.9%). The majority of events occurred in the afternoon (54.4%), in the clinical setting (70.7%), and in 75% of the cases, the search for care occurred within 2 h after exposure. Accidents with needlestick and sharp instruments have high frequency and involve mainly female students. They are more common in the afternoon and in the clinical setting and the time interval was between exposure and the search for care complied with recommendations of the Brazilian legislation.


[Treatment and prognosis of scrotal extramammary Paget's disease: a report of 23 cases].
To evaluate the clinical manifestation, management and prognostic characteristics of scrotal extramammary Pagets disease (EMPD). Twenty-three cases of EMPD were identified and retrospectively reviewed, and the clinical findings, surgical treatment, pathologic features and prognostic characteristics were evaluated. The patients ranged in age from 49 to 72 years (mean 62. 4 years). The diagnoses were delayed by 12 to 132 months (67. 6 on average) in 9 cases at Stage A1 , 12 at A2, 1 at B and 1 at D. The rate of initial misdiagnosis was 91.3% (21/23). Twenty of the patients underwent operations, 2 received radiotherapy and 1 chemotherapy. Twenty-two patients of the total number were followed up for 7 to 223 months, averaging at 119, therapy and 1 chemotherapy. of whom 12 remained cancer free, 1 died of tumor, 3 died of intercurrent disease, 4 experienced local recurrence, 1 relapsed with inguinal lymph node metastasis and 1 developed inguinal lymph node metastasis exclusively. Those with relapses received the second surgery, and 5 of them survived without cancer and 1 died of intercurrent disease. The primary treatment of choice for scrotal EMPD is radical excision. Precise, histological examination before and during the operation is of crucial importance. The positive excisal margins are one of the key causes of local recurrence, and the involvement of dermis by Pagets cells may suggest possible metastasis. Scrotal EMPD tends to occur as a slowly growing lesion, mainly in the elderly, and has a good prognosis in cases of non-invasion. Otherwise the prognosis is poor.


A comparative study of different methods for calculating electronic transition rates.
We present a comprehensive comparison of the following mixed quantum-classical methods for calculating electronic transition rates: (1) nonequilibrium Fermi's golden rule, (2) mixed quantum-classical Liouville method, (3) mean-field (Ehrenfest) mixed quantum-classical method, and (4) fewest switches surface-hopping method (in diabatic and adiabatic representations). The comparison is performed on the Garg-Onuchic-Ambegaokar benchmark charge-transfer model, over a broad range of temperatures and electronic coupling strengths, with different nonequilibrium initial states, in the normal and inverted regimes. Under weak to moderate electronic coupling, the nonequilibrium Fermi's golden rule rates are found to be in good agreement with the rates obtained via the mixed quantum-classical Liouville method that coincides with the fully quantum-mechanically exact results for the model system under study. Our results suggest that the nonequilibrium Fermi's golden rule can serve as an inexpensive yet accurate alternative to Ehrenfest and the fewest switches surface-hopping methods.


Incorporation of presleep stimuli into dream contents: evidence for a consolidation effect on declarative knowledge during REM sleep?
Presleep stimuli to be retained for further recall is often incorporated into dream contents. To establish whether processing for insertion into dream contents may improve consolidation, we compared the retention rate at delayed recall of contents resulting from incorporation of presleep sentence-stimuli with those of other contents of the same dream experiences. We hypothesized that association with a cognitive task of recall facilitates access to recently acquired items of declarative knowledge such as presleep stimuli, and triggers the deep elaboration of their semantic features, which involves rehearsal. Twelve subjects were given a task of delayed recall for three nonsense sentences delivered once a time before each of the sleep (re-)onsets over an experimental night. After each awakening in rapid eye movement sleep, subjects were asked to report dream experience and recall the sentence to be retained. In the morning, after spontaneous awakening, subjects were unexpectedly requested to again report their dream experiences and to recall the stimuli. Two pairs of judges independently identified possible incorporations of the stimuli, and parsed dream reports into propositional content units. The proportion of night reports with at least one incorporation of the stimulus delivered (i.e. valid incorporations) was higher than that of reports with contents similar to a stimulus(-i) not yet delivered (forward pseudo-incorporations) or delivered prior to an earlier sleep period (backward pseudo-incorporations). The proportion of content units common to night and morning reports (considered to be better consolidated) was significantly higher for incorporated contents than for other contents, including pseudo-incorporated contents. Instead, the retention at morning recall of words of sentence-stimuli corresponding to incorporated contents was not significantly higher than that of other words. The better retention of incorporated contents provides a partial confirmation (that is, limited to the output of the processing) that a generation effect, which benefits retention of actively processed information, is operative during sleep as well as in waking.


Element of a validation method for MU-B3 monoclonal antibody using an imaging capillary isoelectric focusing system.
This paper presents an imaging capillary isoelectric focusing (CIEF) assay for the determination of the identity, stability, and isoform distribution of a murine monoclonal antibody (MU-B3). The experiments were conducted using a Convergent Bioscience iCE280 instrument. The optimum carrier ampholyte composition that gave the best peak separation was found to be 25% Pharmalyte pH 3-10 and 75% Pharmalyte pH 5-8. The antibody gave a highly reproducible CIEF profile with three major peaks having average isoelectric point (pI) values of 6.83, 6.99, and 7.11. Intraday and interday reproducibility of pI values was found to be within RSD of 0.5%. The CIEF profile was also the same, with an alternate column cartridge and alternate batches of methyl cellulose. A plot of peak areas versus MU-B3 concentration was linear (R2 = 0.995) up to a concentration of 0.5 mg/mL in the sample solution. Peak area measurements were reproducible to within 7% RSD. The CIEF profiles of two other antibodies were distinctly different from the profile of MU-B3, showing that the assay is specific. After a sample of MU-B3 was subjected to heat stress by exposure to heat at 55 degrees C for 4 h, its CIEF profile was altered with extra peaks appearing at lower pI values, indicating that the assay could be used to monitor stability. The result of the heat stress experiment was also confirmed with a parallel slab-gel IEF analysis of the antibody sample before and after application of the heat stress. The results of this work suggest that imaging CIEF can be used for product testing under a quality control environment. The assay can be used for pI profiling of proteins and for monitoring structural changes (deamidation, glycosylation, etc.) during the manufacturing process and upon storage.


Solvation of an excess electron in pyrrolidinium dicyanamide based ionic liquids.
In a recent article [J. Am. Chem. Soc. 2011, 133, 20186], we described the nature of the "dry" excess electron in a variety of different ionic liquids. We found that this could delocalize over cations or anions depending on the nature of the ions involved. A second article [J. Am. Chem. Soc. 2013, 135, 17528] explored the nature of the "dry to trapped" excess electron transition, the early localization dynamics, and associated spectroscopic signatures in alkylamonium and pyrrolidinium bis(trifluoromethylsulfonyl)amide based ionic liquids. In this study we predicted that the trapped electron localizes on an anion, resulting in fragmentation that is undesirable for photochemical, electrochemical, and radiation chemistry applications. The current work focuses instead on an ionic liquid based on the dicyanamide anion that on a time scale relevant to electron transfer and solvation dynamics does not appear to undergo facile fragmentation. Although electrochemical cathodic and anodic limits were correctly predicted by our recent study, it is unclear whether the reaction channels explored are necessarily those responsible for the observed near-infrared (NIR) band typical of excess electrons at long time. Could it be possible that the electrochemically relevant reaction channel is not necessarily the one giving rise to the NIR signal? This work attempts to approach such structural and dynamical aspects relevant to photodegradation, radiation chemistry, and electrochemistry in the case of pyrrolidinium dicyanamide based ionic liquids.


The multifactorial impact of receiving a hereditary angioedema diagnosis.
Hereditary angioedema (HAE) is a rare, chronic, debilitating genetic disorder characterized by recurrent, unpredictable, and potentially life-threatening episodes of swelling that typically affect the extremities, face, abdomen, genitals, and larynx. The most frequent cause of HAE is a mutation in the serpin family G member 1 (SERPING1) gene, which either leads to deficient plasma levels of the C1-esterase inhibitor (C1-INH) protein (type I HAE-C1-INH) or normal plasma levels of dysfunctional C1-INH protein (type II HAE-C1-INH). Mutations in SERPING1 are known to be associated with dysregulation of the kallikrein-bradykinin cascade leading to enhancement of bradykinin production and increased vascular permeability. However, some patients present with a third type of HAE (HAE-nl-C1-INH) that is characterized by normal plasma levels and functionality of the C1-INH protein. While mutations in the factor XII, angiopoietin-1, plasminogen, kininogen-1, myoferlin, and heparan sulfate-glucosamine 3-O-sulfotransferase-6 genes have been identified in some patients with HAE-nI-C1-INH, genetic cause remains unknown in many cases with further research required to fully elucidate the pathology of disease in these patients. Here we review the challenges that arise on the pathway to a confirmed diagnosis of HAE and explore the multifactorial impact of receiving a HAE diagnosis. We conclude that it is important to continue to raise awareness of HAE because delays to diagnosis have a direct impact upon patient suffering and quality of life. Since many patients will seek help from hospitals during their first swelling attack it is vital that emergency department staff are aware of the different pathological pathways that distinguish HAE from other forms of angioedema to ensure that the most appropriate treatment is administered. As disease awareness increases, it is hoped that patients will be diagnosed earlier and that pre-authorization and insurance coverage of HAE treatments will become easier to obtain, ultimately reducing the burden of treatment for these patients and their caregivers.


Source of group II phospholipase A2 in gastric juice.
Gastric juice contains both pancreatic group I phospholipase A2 (PLA2-I) and synovial-type group II phospholipase A2 (PLA2-II), which may play a crucial role in Helicobacter pylori infection and gastric mucosal injury. PLA2-I present in gastric juice is derived from pancreatic acinar cells. The cellular source of PLA2-II found in gastric juice is unknown. A specific cell type of the intestinal mucosa, the Paneth cell, is known to secrete PLA2-II. The purpose of the present study was to define the source of PLA2-II present in gastric juice. For this purpose, gastric juice was collected from 29 individuals during gastroscopy, and mucosal biopsies were taken from the antrum and body of the stomach and from the duodenum as well as from the jejunum of individuals with resected stomach, for immunohistochemical detection of PLA2-II. The concentration of bilirubin in the gastric juice samples was determined to identify duodenogastric regurgitation. The PLA2-II content was significantly higher in bilirubin-positive than in bilirubin-negative gastric juice samples. PLA2-II was localized by immunohistochemistry in Paneth cells in three patients with areas of intestinal metaplasia of the gastric mucosa and in Paneth cells of duodenal and jejunal mucosa in all patients, but not in any other epithelial cell type of the mucosa of the stomach or the small intestine. Inflammatory cells did not contain PLA2-II. The current results suggest that PLA2-II found in gastric juice is derived from the Paneth cells of the small intestinal mucosa.


Factors Involved in Maintaining Haemostasis in Patients with Myelodysplastic Syndrome.
Etiopathogenesis of myelodysplastic syndrome (MDS) might cause per se an anomalous haemostasis that can be even more deteriorated by thrombocytopaenia. So, evaluation of haemostasis in patients with MDS rises as a necessity.This work aimed to characterize haemostasis in non-bleeder MDS patients with a platelet count similar to healthy controls to establish differences between the two groups not related to thrombocytopaenia.Thromboelastometry in samples from MDS patients suggested the existence of at least two antagonistic processes: one of them giving a hypocoagulable pattern (prolonged clotting time and lower α angle) and another conferring a procoagulant profile (decreased fibrinolysis). Hypocoagulable state might be due to a decreased ability of platelets to be stimulated and to the presence in plasma of a factor/s that prolonged the time to initiate thrombin generation. This factor/s might be antibodies as this effect was observed in samples from MDS patients with an associated autoimmune-inflammatory condition.Otherwise, hypercoagulable state seemed to rely on an increased presence of red cell- and monocyte-derived microparticles and to the increased exposure of phosphatidylserine that served as scaffold for binding of coagulation factors.We concluded that haemostasis in MDS patients is a complex process influenced by more factors than platelet count.


Effect of Wavefront Aberrations on Night Vision Problems and Mesopic Contrast Threshold After SMILE.
To investigate the effect of wavefront aberrations on night vision problems and mesopic contrast threshold after small incision lenticule extraction (SMILE). Forty-two participants (84 eyes) who underwent SMILE were included in this prospective observational study. Visual outcomes including uncorrected distance visual acuity (UDVA), subjective manifest refraction, mesopic contrast threshold (Binoptometer 4P; Oculus Optikgeräte GmbH), and higher order aberrations (HOAs) were analyzed before and 3 months after surgery. The patient's night vision satisfaction was assessed using a questionnaire. The mean spherical equivalent was -5.30 ± 1.38 diopters (D) preoperatively and -0.06 ± 0.15 D postoperatively. UDVA was better than 20/20 in 98.81% of the patients and better than 20/25 in all patients. Scores of night vision satisfaction and glare changed significantly in the postoperative period (F = 8.463, P = .001; F = 69.518, P < .001, respectively). Preoperative spherical diopters (lower order aberrations) were positively correlated with night vision satisfaction (r = -0.329, P = .041) and glare score (r =-0.332, P = .039). Age (odds ratio [OR] = 1.272, 95% CI = 1.019 to 1.589) and preoperative spherical diopter (OR = 0.437, 95% CI = 0.199 to 0.975) were correlated with night vision satisfaction scores by analysis of binary regression. The root mean square value of total HOAs increased 3 months after surgery (t = -6.873, P < .001) with an increase in horizontal coma (Z31) and spherical aberration (Z40) (P < .001). No correlation was observed between glare score and HOAs; however, patients with higher preoperative myopia demonstrated continuously decreasing contrast under mesopic conditions and higher postoperative horizontal coma. Myopic patients with higher preoperative spherical errors experienced more glare at night after SMILE surgery. Postoperative horizontal coma was associated with worse mesopic contrast thresholds. [J Refract Surg. 2021;37(7):446-452.].


Infants in play groups: time related changes in behavior toward mothers, peers, and toys.
Twenty-one 13-month-old infants, nine male and 12 female, were assigned to one of seven playgroups convening for 15 consecutive weekdays . Present at each 20-minute play session were three same-sexed peers with their mothers and an assortment of toys. There were systematic fluctuations in infants' attention to mother, peers, and toys. There findings suggest that a mother may serve different functions at different points in time: (a) as a secure base in initial sessions, (b) as a refueling stop when the infant grew tired, and (c) as an attractive alternative when the infant became bored with toys and peers. Within-day analyses revealed that activity level and toy exploration linearly decreased over time, while intentional contact with mother significantly increased. Social interaction with peers correlated negatively with interaction with mother over the course of the study. Sex differences over time were found to be significant: boys on day one were more interactive with both peers and toys but this level declined thereafter, while girls on day one spent more time in close proximity to mother and later, on subsequent days, increased their peer and toy play.