The role of nitric oxide in the modulation of hepatic microcirculation and tissue oxygenation in an experimental model of hepatic steatosis.
Impairment of hepatic microcirculation in fatty liver has been assumed to reduce tolerance of the liver against ischemia-reperfusion injury. The present study was aimed to investigate the role of nitric oxide (NO) in the regulation of hepatic microcirculation and tissue oxygenation in hepatic steatosis. Sprague-Dawley rats (200-250 g) were fed a 2% cholesterol diet (n = 12) to induce hepatic steatosis or normal diet (n = 12) served as controls for 12 weeks. Hepatic blood flow, microcirculation, tissue oxyhemoglobin (HbO2) and cytochrome c oxidase radox status (Cyt Ox) in response to intravenous bolus administrations of l-arginine (300 mg/kg) or l-NAME (20 mg/kg) were assessed. Animals which developed moderate hepatic steatosis showed significant increase in tissue level of total lipids. Portal blood flow and hepatic microcirculation were significantly reduced as compared to controls (5.7 +/- 0.9 vs. 9.7 +/- 0.9 ml/min, P = 0.003 and 114.5 +/- 9.5 vs. 167.3 +/- 10.0 flux unit, P = 0.003). l-Arginine improved hepatic arterial and portal blood flows as well as microcirculation in fatty livers (P < 0.05), while l-NAME significantly worsened these parameters (P < 0.05). Hepatic tissue HbO2 and Cyt Ox were improved both in fatty and control livers following l-arginine, while l-NAME resulted in decreased HbO2 and Cyt Ox although a transit increase in tissue oxygenation was observed in fatty livers. NO is involved in the modulation of hepatic microcirculatory perfusion and oxygenation in cholesterol-induced hepatic steatosis. NO metabolisms may be regulated as a potential therapeutic strategy for impaired microcirculation in hepatic steatosis.


Effect of smoking on caffeine clearance.
The elimination of caffeine from saliva was compared in groups of healthy smokers (n = 13) and nonsmokers (n = 13). Mean caffeine t1/2 in smokers (3.5 hr) was shorter than that in the nonsmokers (6.0 hr). The body clearance of caffeine in the smokers (155 +/- 16 ml . kg-1 . hr-1) was greater than that in the nonsmokers (94 +/- 18 ml . kg-1 . hr-1) (p less than 0.05). No significant difference was noted in the apparent volume of distribution in smokers (720 +/- 67 ml . kg-1) and nonsmokers (610 +/- 80 ml . kg-1). These differences probably reflect the induction of hepatic aryl hydrocarbon hydroxylase (AHH) activity in smokers. The increased clearance of caffeine by smokers may contribute to the higher consumption of coffee reported to occur in this group.


The Impact of Ramadan on Patient Attendance Patterns in an Emergency Department at a Tertiary Care Center in Beirut, Lebanon.
Emergency departments (EDs) worldwide experience substantial variability in hourly patient arrivals. The month of Ramadan represents a repetitive annual occurrence, which could be associated with distinct patient arrival patterns compared with other months of the year. This study examined hourly patient arrival patterns and patient characteristics in an ED in a tertiary care center in Beirut, Lebanon to determine whether there are significant changes in patient attendance patterns during the month of Ramadan. Data on patients presenting to the ED during the month of Ramadan with those presenting 1 month prior to and 1 month after, between 2012 and 2018, were accounted for in the study. Pearson chi-squared test was used in the bivariate analysis, whereas Student's t-test was used to compare continuous variables. Patient attendance patterns significantly varied between Ramadan and non-Ramadan periods (p < 0.0001). Patient flow dropped starting at 8:00 am, with the greatest drop between 6:00 pm and 9:00 pm, and increased in the early morning hours between 2:00 am and 4:00 am (p < 0.0001). The total number of visits per day significantly decreased in Ramadan compared with non-Ramadan periods (135.6 ± 14.74 vs. 145.5 ± 18.90, p-value < 0.0001), whereas length of stay decreased slightly. We found a drop in daily ED visits during Ramadan, in addition to a distinct pattern of patient arrivals. ED administrators should consider different scheduling arrangements for nurses and physicians during this period in EDs that serve communities where Ramadan is commonly observed.


Clinical and cytologic characteristics of allergic rhinitis in elderly patients.
The constant increase in the elderly population worldwide has led to a greater interest in immunologic responses during aging. Thus, special attention to allergic diseases in elderly people has begun to emerge, but little is known about the effect and features of allergic rhinitis in elderly people. To evaluate the clinical and cytologic characteristics of respiratory allergy and its impact on the quality of life in elderly people. Elderly patients with rhinitis referred to our allergy unit during a 3-month period underwent clinical evaluation and responded to the Rhinasthma Questionnaire. All patients also underwent skin prick testing, measurement of total IgE level, and nasal cytologic analysis. The data were compared with a control group of young adults. Fifty-four patients older than 65 years (mean age, 69.3 years) and 89 young adults (mean age, 26.3 years) with allergic rhinitis were studied. The elderly patients had a less positive family history of atopy (P=.02) and had rhinitis plus conjunctivitis more frequently (P=.002) than young adults, whereas the difference between groups in total IgE level was not statistically significant. On nasal cytologic analysis, the differential count of inflammatory cells did not differ between groups, but in the elderly patients the epithelial-goblet cell ratio was decreased. The quality of life in elderly people was more impaired than in young adults (P=.01). In elderly people with allergic rhinitis, the clinical characteristics are different and quality of life is more heavily impaired compared with young adults.


Client perceptions of satisfaction with AIDS services: an instrument development.
The purpose of this article is to show how AIDS Service Organizations (ASOs) can develop their own instruments to assess client satisfaction by using support from academic partners. The Client Satisfaction Questionnaire (CSQ) is an example of this process. The initial 12-item CSQ was piloted using a sample of 46 HIV-infected men and women, resulting in a revised 8-item CSQ that was assessed by using a sample of 121 HIV-infected men and women. The initial CSQ (12-item) yielded three factors, volunteer's skill/access, volunteer's attitude, and volunteer's caring, accounting for 74.6% of the explained variance (Cronbach's alpha = 0.84). The revised CSQ (8-item) resulted in one factor accounting for 67% of the explained variance (Cronbach's alpha = 0.92). Findings indicated acceptable reliability and validity of the CSQ to assess client satisfaction as an outcome of ASO client-agency interaction. Guidelines for instrument development by ASOs are proposed. Strategies to collaborate with the academic community to facilitate instrument development are discussed.


Chorea as a symptom of neuroborreliosis: a case study.
Borrelia burgdorferi (Bb) can cause a large number of neurological symptoms. Although extrapyramidal disturbances are rare (representing less than 2% of all neurological complications), diffuse choreic dyskinesias have been described during the course of mild encephalitis. The data published in the literature suggest that there are clinical and neurological analogies between neuroborreliosis and multiple sclerosis (MS). The presence of specific anti-Bb antibodies in cerebrospinal fluid is a discriminating factor that allows a diagnosis of neuroborreliosis to be made. We describe the case of a patient with Lyme disease, characterised by widespread chorea and behavioural disturbances. Emphasis is placed on the atypical onset and evolution, the difficulties encountered in formulating a diagnosis, and the uncertainties concerning the pathophysiology and clinical/neuroradiological correlations of the disease.


Perceived Social Norms Guide Health Care Decisions for Oneself and Others: A Cross-Sectional Experiment in a US Online Panel.
Global aging has increased the reliance on surrogates to make health care decisions for others. We investigated the differences between making health care decisions and predicting health care decisions, self-other differences for made and predicted health care decisions, and the roles of perceived social norms, emotional closeness, empathy, age, and gender. Participants (N = 2037) from a nationally representative US panel were randomly assigned to make or to predict a health care decision. They were also randomly assigned to 1 of 5 recipients: themselves, a loved one 60 y or older, a loved one younger than 60 y, a distant acquaintance 60 y or older, or a distant acquaintance younger than 60 y. Hypothetical health care scenarios depicted choices between relatively safe lower-risk treatments with a good chance of yielding mild health improvements versus higher-risk treatments that offered a moderate chance of substantial health improvements. Participants reported their likelihood of choosing lower- versus higher-risk treatments, their perceptions of family and friends' approval of risky health care decisions, and their empathy. We present 3 key findings. First, made decisions involved less risk taking than predicted decisions, especially for distant others. Second, predicted decisions were similar for others and oneself, but made decisions were less risk taking for others than oneself. People predicted that loved ones would be less risk taking than distant others would be. Third, perceived social norms were more strongly associated than empathy with made and predicted decisions. Hypothetical scenarios may not adequately represent emotional processes in health care decision making. Perceived social norms may sway people to take less risk in health care decisions, especially when making decisions for others. These findings have implications for improving surrogate decision making. People made less risky health care decisions for others than for themselves, even though they predicted others would make decisions similar to their own. This has implications for understanding how surrogates apply the substituted judgment standard when making decisions for patients.Perceived social norms were more strongly related to decisions than treatment-recipient (relationship closeness, age) and decision-maker (age, gender, empathy) characteristics. Those who perceived that avoiding health care risks was valued by their social group were less likely to choose risky medical treatments.Understanding the power of perceived social norms in shaping surrogates' decisions may help physicians to engage surrogates in shared decision making.Knowledge of perceived social norms may facilitate the design of decision aids for surrogates.


Genomics of pain in osteoarthritis.
Osteoarthritis (OA) accounts for the majority of the disease burden for musculoskeletal disorders and is one of the leading causes of disability worldwide. This disability is the result not of the cartilage loss that defines OA radiographically, but of the chronic pain whose presence defines symptomatic OA. It is becoming clear that many genes, each with a small effect size, contribute to the risk of developing OA. However, the genetics of OA pain are only just starting to be explored. This review will describe the first genes to have been identified in genomic studies of OA pain, as well as the possible dual roles of genes previously identified in genomic studies of OA in the context of pain. Difficulties associated with attempting to characterise the genetics of OA pain will be discussed and promising future avenues of research into genetic and epigenetic factors affecting OA pain described.


Short-term changes in Bruch's membrane opening-based morphometrics during the first week after trabeculectomy.
To evaluate the dynamics of Bruch's membrane opening-based morphometrics of the optic nerve head (ONH) using spectral-domain optical coherence tomography (SD-OCT) during the first week after glaucoma surgery by trabeculectomy with mitomycin C. Prospective, longitudinal analysis of 25 eyes of 25 patients treated by trabeculectomy. Twenty-four eyes had evaluable postoperative SD-OCT examinations. Bruch's membrane opening minimum rim width (BMO-MRW) and peripapillary retinal nerve fiber layer (RNFL) thickness were analyzed at baseline before surgery, 1 day, 2 to 3 days, and 1 week after surgery. Changes compared to baseline were correlated to intraocular pressure (IOP). One day after surgery, the mean BMO-MRW changed by + 26.17 µm, p = 0.001 (mean IOP reduction by 17.01 mmHg). This increase persisted on day 2-3 with a mean increase of BMO-MRW of + 25.33 µm, p = 0.001 (mean IOP reduction by 20.46 mmHg) and by week 1 with a mean BMO-MRW increase of + 33.17 µm, p < 0.001 (mean IOP reduction by 22.55 mmHg). The increase in BMO-MRW correlated significantly with the reduction of IOP on day 1 (Spearman's rho ρ = 0.656, p = 0.003) and d2-3 (Spearman's rho ρ = 0.479, p = 0.038). There was no statistically significant correlation found between the IOP and the increase in BMO-MRW in week 1. RNFL thickness showed no significant changes at day 1 as well as days 2-3 (p ≥ 0.078, respectively). It showed a small but significant increase in week 1 by 3.94 µm, p = 0.015. Structural reversal of disc cupping in BMO-MRW occurs as early as 1 day after trabeculectomy and correlates to the extent of the IOP reduction. During the whole first week after surgery, a strong increase in BMO-MRW can be noted. The changes in BMO-based parameters need to be considered when evaluating patients' longitudinal follow-up.


Percutaneous needle localisation of breast lesions prior to biopsy: analysis of failures.
Mammography can detect clinically occult breast cancer. But with minimal or no physical findings the lesion can be quite difficult for the surgeon to find within the recumbent breast at biopsy. Percutaneous needle localisation, the placement of a needle in or in the vicinity of such a clinically silent lesion, provides an internal landmark to assist the surgeon. Review of our experience of 90 procedures using this technique disclosed a success rate of approximately 90%. The biopsies diagnosed 14 cancers before local or distant metastasis could be found. The eleven of the fourteen who had axillary dissection were found to have negative nodes. Identifiable causes of failure were sought and discussed in the 7 documented failures. Faulty needle placement was judged noncontributory in all but one case. Needle movement between time of placement and time of biopsy could never be excluded and is in fact suspected in two failures. Immediate re-sampling, or larger initial specimens would have salvaged the procedure in most instances of failure. We feel poor communication and poor mutual understanding of the localization procedure to be the major contributing cause of failure. Even so, we have been able to use the technique with 90% success. The development of mammography brought with it the opportunity to detect small non-palpable carcinomas and the surgical problem of removing them at biopsy. While the suspect lesions identified by mammography are frequently benign, the cancers found are usually small and some only microscopic in size. The literature contains many descriptions of various techniques for localising such lesions prior to biopsy. We are reporting our experience with percutaneous needle localisation. To our knowledge, we have the distinction of being the first to report difficulty with a localisation technique and will analyse possible reasons. Some of the problems are common to all the localisation techniques.


Progressive compensatory symbiosis: spouse caregiver experiences of caring for persons with dementia in Taiwan.
Spouse caregivers have been the predominant family members who care for persons with dementia in Taiwan. Although studies in western countries have described the caregiving experiences and changes in the marital relationship for these spouse caregivers, this information is lacking in Taiwan. This study explored the experiences of spouse caregivers caring for persons with dementia in Taiwan. A grounded theory approach was used for this qualitative descriptive study. Data were collected through recorded in-depth interviews and observations with 15 spouse caregivers of persons with dementia. Constant comparative analysis was used to analyse the transcripts and field notes. Analysis of interview transcripts revealed that the experiences of caregiving for spouse caregivers who lived with persons with dementia could be described as 'progressive compensatory symbiosis.' This core category included three components: awareness of unbalanced intimacy, making a commitment and implementing a compensatory scheme. These experiences could be either mutually beneficial or unbalanced and fluctuated as the disease progressed through the phases of 'subtle,' 'revealed' and 'confirmed,' which also influence the pace, transition and evolution of the compensatory symbiosis. This exploratory study describes the family caregiving experiences for 15 spouse caregivers of persons with dementia in Taiwan. These results can provide guidance for developing interventions to prepare, facilitate and promote a mutually beneficial adjustment for spousal caregivers and their spouses as dementia progresses. The findings are worthy of further investigation with a larger sample and a prospective design.


SRP54 mutations induce congenital neutropenia via dominant-negative effects on XBP1 splicing.
Heterozygous de novo missense variants of SRP54 were recently identified in patients with congenital neutropenia (CN) who display symptoms that overlap with Shwachman-Diamond syndrome (SDS). Here, we investigate srp54 knockout zebrafish as the first in vivo model of SRP54 deficiency. srp54-/- zebrafish experience embryonic lethality and display multisystemic developmental defects along with severe neutropenia. In contrast, srp54+/- zebrafish are viable, fertile, and show only mild neutropenia. Interestingly, injection of human SRP54 messenger RNAs (mRNAs) that carry mutations observed in patients (T115A, T117Δ, and G226E) aggravated neutropenia and induced pancreatic defects in srp54+/- fish, mimicking the corresponding human clinical phenotypes. These data suggest that the various phenotypes observed in patients may be a result of mutation-specific dominant-negative effects on the functionality of the residual wild-type SRP54 protein. Overexpression of mutated SRP54 also consistently induced neutropenia in wild-type fish and impaired the granulocytic maturation of human promyelocytic HL-60 cells and healthy cord blood-derived CD34+ hematopoietic stem and progenitor cells. Mechanistically, srp54-mutant fish and human cells show impaired unconventional splicing of the transcription factor X-box binding protein 1 (Xbp1). Moreover, xbp1 morphants recapitulate phenotypes observed in srp54 deficiency and, importantly, injection of spliced, but not unspliced, xbp1 mRNA rescues neutropenia in srp54+/- zebrafish. Together, these data indicate that SRP54 is critical for the development of various tissues, with neutrophils reacting most sensitively to the loss of SRP54. The heterogenic phenotypes observed in patients that range from mild CN to SDS-like disease may be the result of different dominant-negative effects of mutated SRP54 proteins on downstream XBP1 splicing, which represents a potential therapeutic target.


Natural Bioactive Compounds against Oxidative Stress: Dietary Polyphenols Strike Back.
Oxidative stress is a major cellular and metabolic burden that can really alter cell life and become the base for disease onset and development. Many widespread pathologies can develop from an unresolved oxidative stress situation; thus, addressing this state is paramount for human health. Our antioxidant enzymes sometimes are not just enough. Fortifying our defense and the antioxidant and anti-inflammatory system can make a difference in our health: if this is attainable with our dietary habits, it could be a dream come true. Polyphenols are a fantastic tool indeed in the fight against oxidative stress: they are easy to obtain, with little cost, no side effects, and have a multitude of metabolic actions. This perspective review would shed light on polyphenol's metabolic and molecular action regarding oxidative stress to help preserve our health.


Expression of S100A8 protein on B cells is associated with disease activity in patients with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is an intractable disease characterized by autoantibody production and autoreactive B and T cell proliferation. Although several studies have revealed multiple genetic and environmental associations, the underlying mechanisms remain unknown. We performed proteomics and transcriptomics using liquid chromatography-mass spectrometry and DNA microarray, using peripheral blood B cells from patients with SLE, and healthy controls (HC). We explored molecules associated with the pathophysiology of SLE by flow cytometry and B cell stimulation assay. We identified for the first time that expression of both S100A8 protein and mRNA were markedly upregulated in SLE B cells. The results obtained using flow cytometry showed that S100A8 was highly expressed on the surface of B cells of patients with active SLE (MFI; HC 102.5 ± 5.97, stable SLE 111.4 ± 12.87, active SLE 586.9 ± 142.9), and S100A8 on the cell surface was decreased after treatment (MFI; pre-treat 1094.5 ± 355.38, post-treat 492.25 ± 247.39); therefore, it is suggested that S100A8 may be a marker for disease activity. The mRNA expression of S100A8 was particularly upregulated in memory B cells of SLE (56.68 fold higher than HC), suggesting that S100A8 may be mainly secreted by memory B cells in the pathogenesis of SLE. Our results imply that the S100A8 proteins secreted from memory B cells may stimulate granulocytes and monocytes through pattern recognition receptors, activate the innate immune system, and are involved in the pathogenesis of SLE.


The in situ kinetics of dopamine beta-hydroxylase in bovine adrenomedullary chromaffin cells. Intravesicular compartmentation reduces apparent affinity for the cofactor ascorbate.
The Km of dopamine beta-hydroxylase for its cofactor, ascorbic acid, was determined in situ in primary cultures of bovine adrenomedullary chromaffin cells and in isolated chromaffin vesicles. A range of intravesicular ascorbate concentrations in chromaffin cell cultures (1.1-31.2 mM) was achieved by varying the number and concentration of ascorbate additions to the culture media. The rate of octopamine synthesis from tyramine displayed a Michaelis-Menten relationship with respect to ascorbate concentration and an apparent Km of dopamine beta-hydroxylase for ascorbate of 15.0 +/- 2.0 mM was determined. In isolated chromaffin vesicles, with an initial intravesicular ascorbate concentration of approximately 10 mM, ascorbate consumption during beta-hydroxylation occurred as a first order process. This indicated that dopamine beta-hydroxylase was not saturated at this initial ascorbate concentration. When isolated chromaffin vesicles were prepared with different intravesicular ascorbate concentrations, the rate of octopamine synthesis displayed a Michaelis-Menten relationship with respect to ascorbate with an apparent Km of 17.0 +/- 5.0 mM. Ascorbate consumption also occurred as a first order process in ascorbate-loaded chromaffin-vesicle ghosts which had initial ascorbate concentrations of approximately 30 mM but which were depleted of other small molecules such as catecholamines. These results indicate that the in situ Km of dopamine beta-hydroxylase for ascorbate (approximately 15 mM) is 25-fold higher than it is for the purified or partially purified enzyme assayed under optimal conditions in vitro (0.6 mM). The factor(s) which decreases the enzyme affinity for ascorbate, relative to in vitro, resides in the chromaffin vesicle interior and is also retained in chromaffin-vesicle ghosts. The mechanism of this effect remains to be determined. The Km value determined in these experiments is close to the estimated intravesicular ascorbate concentration of bovine chromaffin granules in vivo (4), suggesting that the availability of ascorbate could become a factor in regulating the rate of dopamine beta-hydroxylation.


Enacted HIV-Related Stigma's Association with Anxiety & Depression Among People Living with HIV (PLWH) in Florida.
Research has shown that HIV-related stigma contributes to people living with HIV having a higher risk of mental health disorders. Our study examines the association between enacted HIV-related stigma and symptoms of anxiety and depression among PLWH. We used baseline data from 932 PLWH collected from the Florida Cohort study between 2014 and 2018. The sample was majority 45 + years of age (63.5%), male (66.0%), and Black (58.1%). The majority had previously experienced enacted HIV-related stigma (53.1%). Additionally, 56.6% and 65.2% showed mild to moderate/severe levels of anxiety and depression, respectively. Those who experienced any levels of enacted HIV-related stigma (vs none) had significantly greater odds of mild and moderate/severe levels of anxiety (vs no/minimal) (AOR[CI] 1.54[1.13, 2.10], p = 0.006; AOR[CI] 3.36[2.14, 5.26], p < 0.001, respectively) and depression (AOR[CI] 1.61[1.19, 2.18], p = 0.002; AOR[CI] 3.66[2.32, 5.77], p < 0.001, respectively). Findings suggest a need to evaluate interventions for PLWH to reduce the deleterious effects of enacted HIV-related stigma on mental health.


Primary Kaposi's sarcoma of the nasal cavity not associated with AIDS.
Kaposi's sarcoma (KS) is an unusual vascular tumor characterized by multiple reddish blue nodules, which usually present on the skin of the lower and upper extremities. KS may also involve mucosal sites, lymph nodes and visceral organs. During the last two decades, with the large increase in the incidence of this tumor associated with the acquired immune deficiency syndrome (AIDS), there have been increasing number of cases with KS presenting on the skin or mucosa of the head and neck. A review of the literature revealed that only six cases of primary KS of the nasal cavity have previously been published and only one of them presented in a patient not associated with AIDS. We report the case of a 59-year-old woman who presented 4 years ago with nasal obstruction and intermittent minor epistaxes. Physical examination revealed the presence of a fleshy tumor arising from the left nasal septum, which was excised. Histological examination of the tumor showed morphological and immunohistochemical features of KS. A complete physical and laboratory examination revealed no other pathological findings. The patient received no further treatment and 4 years later, she is in excellent condition. In the present study, we report the second case where the primary manifestation of the KS was in the nasal cavity in a patient with an adequate immune system.


Cytotoxicity Evaluation of Anatase and Rutile TiO₂ Thin Films on CHO-K1 Cells in Vitro.
Cytotoxicity of titanium dioxide (TiO₂) thin films on Chinese hamster ovary (CHO-K1) cells was evaluated after 24, 48 and 72 h of culture. The TiO₂ thin films were deposited using direct current magnetron sputtering. These films were post-deposition annealed at different temperatures (300, 500 and 800 °C) toward the anatase to rutile phase transformation. The root-mean-square (RMS) surface roughness of TiO₂ films went from 2.8 to 8.08 nm when the annealing temperature was increased from 300 to 800 °C. Field emission scanning electron microscopy (FESEM) results showed that the TiO₂ films' thickness values fell within the nanometer range (290-310 nm). Based on the results of the tetrazolium dye and trypan blue assays, we found that TiO₂ thin films showed no cytotoxicity after the aforementioned culture times at which cell viability was greater than 98%. Independently of the annealing temperature of the TiO₂ thin films, the number of CHO-K1 cells on the control substrate and on all TiO₂ thin films was greater after 48 or 72 h than it was after 24 h; the highest cell survival rate was observed in TiO₂ films annealed at 800 °C. These results indicate that TiO₂ thin films do not affect mitochondrial function and proliferation of CHO-K1 cells, and back up the use of TiO₂ thin films in biomedical science.


An efficient one pot transfer hydrogenation and N-alkylation of quinolines with alcohols mediated by Pd/C/Zn.
A Pd/C/Zn mixture with alcohols has been revealed to be an efficient transfer hydrogenation system to quinolines. Furthermore, the metals mixture is able to activate alcohols as N-alkylating agents in a hydrogen autotransfer process. 1,2,3,4-Tetrahydroquinolines and N-alkylated tetrahydroquinolines from quinolines have been obtained with excellent yields in one step.


Age-related changes in neural trace generation of rule-based auditory features.
Young (M = 22) and elderly volunteers (M = 74) participated in an ERP study that examined rule-based feature ion in the auditory modality. Stimuli were either a frequent ascending tone pair or an infrequent descending tone pair. Tone-pairs were presented under three conditions. Physical feature monaural (1 tone pair), feature monaural (10 tone pairs), and feature binaural (10 tone pairs). Volunteers watched a silent movie during ERP recordings. After completion of the ERP session all volunteers participated in a behavioral discrimination task. MMNs were elicited under all three conditions for the young. For the elderly, MMNs were elicited under both monaural conditions but not under binaural conditions. Behavioral discrimination was high under the physical feature condition but fell to near chance under the two rule-based feature conditions for both age groups. Thus rule-based neural representations were generated for both age groups under monaural conditions, but only for the young under binaural conditions, suggesting that there is an age-related decline in the efficacy of integrating multiple sources into a single auditory stream.


Indicators of job quality in the Australian aged care workforce: A scoping review.
As governments grapple with ageing populations, there is a need to understand more about the aged care workforce and how it is managed. We undertook a scoping review according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Scopus and PubMed were used to identify papers published between 2010 and 2020. We mapped the breadth and scale of the evidence base according to the QuInnE indicators of job quality. Out of 642 titles and abstracts that were screened, 122 were selected. Outcomes were measured across a range of domains, including wages, employment quality, education and training, working conditions, work/life balance and consultative participation and collective representation. These were distributed unevenly, revealing evidence gaps. We identified significant knowledge gaps regarding Australia's aged care workforce at a time when the sector is coming under fresh scrutiny and projections indicate that it will face critical labour shortfalls going forward.


MR evaluation ex vivo and in vivo of a covered stent-graft for abdominal aortic aneurysms: ferromagnetism, heating, artifacts, and velocity mapping.
Magnetic resonance imaging (MRI) safety was evaluated at 1.5 T in a covered nickel titanium stent-graft (Vanguard) used for endovascular treatment of abdominal aortic aneurysms (AAAs). Imaging artifacts were assessed on MRI with contrast-enhanced (CE) three-dimensional (3D) MR angiography (MRA) and spiral computed tomography (CT) in 10 patients as well as ex vivo. Velocity mapping was performed in the suprarenal aorta and femoral arteries in 14 patients before and after stent-graft placement. For comparison it was also performed in six healthy volunteers. No ferromagnetism or heating was detected. Metal artifacts caused minimal image distortion on MRI/MRA. The artifacts disturbed image evaluation on CT at the graft bifurcation and graft limb junction. No significant differences in mean flow were found in patients before and after stent-graft placement. Our study indicates that MRI at 1.5 T may be performed safely in patients with the (Vanguard) stent-graft. MRI/MRA provides diagnostic image information. Velocity mapping is not included in our routine protocol.


Optical quality of the eye after lens replacement with a pseudoaccommodating intraocular lens.
To examine the optical quality of healthy presbyopic eyes before and after implantation of the pseudoaccommodating AcrySof ReSTOR Natural intraocular lens (IOL) (Alcon Laboratories) by measuring visual acuity and wavefront aberrations. University of Valencia, Fernández-Vega Ophthalmological Institute, Valencia, Spain. Monocular refraction and photopic distance (6 m) and near (0.33 m) visual acuities were determined before and after clear lens extraction with bilateral AcrySof ReSTOR Natural IOL implantation in 30 hyperopic eyes (+0.50 to +4.00 diopters [D]) of presbyopic patients with low astigmatism (< or = 1.00 D). Postsurgical binocular visual acuity was measured over a range of effective distances. Wavefront aberrations were measured before and after surgery. Aberrations for 2 pupil diameters (3.0 mm and 5.0 mm) were decomposed using Zernike polynomials; total, defocus, astigmatism spherical, and coma aberration terms were studied separately. Postimplantation results were compared with preoperative values. Safety and efficacy indices for distance vision were 1.01 and 0.96, respectively. At near, they improved to 1.07 and 1.06, respectively. Vision at intermediate distances was noticeably poorer. Total, defocus, and spherical aberrations changed after IOL implantation with both pupil diameters (P<.01). Total and defocus aberrations were significantly reduced postoperatively. Spherical aberration coefficients changed to negative and less positive values for a 3.0 mm and a 5.0 mm pupil, respectively. Implantation of the pseudoaccommodating IOL in healthy eyes yielded uncorrected levels of high-contrast, distance, and near acuities comparable to preoperative best corrected values. Higher-order aberration levels appeared to be similar to the preoperative values.


Corneal infections in the 21st century.
Ninety years ago, the first issue of the Postgraduate Medical Journal published a review of an article written by Mr Robert Lindsay-Rea, a consultant ophthalmic surgeon in the Western Ophthalmic Hospital and an oculist in the West End Hospital for Nervous Diseases, entitled "A preliminary report on the treatment of keratitis". Today, microbial keratitis remains an important cause of avoidable visual impairment in the world. The aetiology of microbial keratitis has changed greatly over the past century due to the discovery of antibiotics, improvement in sanitation and education, the rising trend of contact lens wear and increased air travel. Significant advances have also been made in our understanding and management of this important disorder. This article highlights some of these changes and discusses the current management and research.


Hostility, anger expression, cardiovascular responsivity, and social support.
Sixty male subjects completed the Cook-Medley Hostility Scale (Ho), the anger-in, anger-out, and anger-discuss measures of anger expression from the Framingham Heart Study, and a measure of social support. Subjects also performed two challenging tasks while systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate (PR) were monitored. Neither SBP, DBP, nor PR responses to the tasks were found to be related to the Ho or anger expression scales. Quality of social support was not found to be related to the Ho scale but was related negatively to the anger-discuss scale. The more subjects reported discussing their anger with others, the less social support they reported having. A negative correlation was found between the Ho and anger-out scales. The possibility is discussed that the relation between either of these two measures and coronary heart disease may be mediated or moderated by the other variable.


Voices from beyond the grave: The impact of apoptosis on the microenvironment.
Programmed cell death, in particular apoptosis, has vital functions in every healthy organism. In a highly regulated manner cells which are no longer needed or are harmful to the organism undergo suicide. More than just the mere elimination of a cell, apoptosis is increasingly being recognized performing important roles in cellular communication with the microenvironment. These interactions with surrounding cells can have various, and sometimes competing outcomes. Apoptotic cells can promote survival, proliferation and inflammation, but depending on the context also prevent survival and inflammation. In this review, we will summarize the emerging literature on how dying cells can transfer information to their neighbours, and which outcomes this communication has for the whole tissue.


Perinatal administration of nicotine alters subsequent sexual behavior and testosterone levels of male rats.
The effect of pre- and/or postnatal administration of nicotine (0.25 mg/kg) on sexual behavior and testosterone levels in adult male rats was examined. Prenatal nicotine decreases male sexual behavior as measured by the number of males that mounted, intromitted or ejaculated. The males that did mount and/or ejaculate exhibited an increase in mount latency and number of mounts and a decrease in efficiency. This decrease was correlated with a decrease in plasma testosterone levels. Postnatal nicotine treatment improved the sexual performance of sexually naive males as measured by an increase in the number of males that completed 2 ejaculatory series and by a decrease in mount latency. This effect is transient, subsequent testing of the nicotine males eliminated this difference in sexual performance. Pre- and postnatal nicotine treatment did not affect the overall sexual performance of the male rats, although the number of mounts and intromissions during a second series decreased. Eye opening of male and female pups was accelerated with pre/postnatal nicotine administration. Birth weight, testis and levator ani weights, sex ratio and number of pups per litter were not affected. We suggest that nicotine may act as a neuromodulator during sexual differentiation of the brain, demasculinizing the male progeny in rats. This effect is correlated with decreased testosterone levels during adulthood.


Diagnostic accuracy of 64-slice CT in evaluating coronary artery bypass grafts and of the native coronary arteries.
Our aim was to evaluate the accuracy, sensitivity and specificity of 64-slice multidetector computed tomography (MDCT) in the assessment of occlusions and stenoses of arterial and venous bypass grafts and disease progression in the native vessels distal to the graft, and to compare the results with those of conventional coronary angiography. We enrolled 78 individuals (45 men, 33 women; mean age 59) and evaluated 213 bypass grafts using a 64-slice MDCT scanner. All patients underwent conventional coronary angiography with a mean time interval between the two examinations of 2 days. One patient was excluded due to arrhythmia during the examination. The 212 bypass grafts in the remaining 77 patients (98.7%) consisted of 115 (54%) venous grafts and 97 (46%) arterial grafts. In the 115 venous grafts, MDCT showed a sensitivity, specificity and accuracy of 100% in evaluating occluded grafts and a sensitivity of 94.4%, specificity of 98.4% and accuracy of 96.9% in evaluating significant stenoses. In evaluating occluded arterial grafts, sensitivity was 83.3%, specificity 100% and accuracy 98.9%, whereas in evaluating stenoses of arterial grafts, sensitivity was 100%, specificity 97.7% and accuracy 98%. Sensitivity, specificity and accuracy in evaluating native coronary vessels distal to the graft allow for a complete assessment of the surgical and native circulation. The examination appears therefore to be exhaustive in ruling out or confirming the presence of diseased vessels in the postoperative follow-up.


Decreased numbers of CD4+ T lymphocytes in peripheral blood after treatment of childhood acute lymphoblastic leukemia.
Treatment-related immunosuppression in patients with acute lymphoblastic leukemia (ALL) is associated with increased susceptibility to infectious diseases, also after the treatment. The aim of the present study was the detailed evaluation of T lymphocyte subsets in peripheral blood in children after treatment of ALL. All children were treated according to the BFM 90 protocol. The patients were divided into 5 groups of 30 children in each, depending on the time from cessation of the ALL treatment. A control group consisted of 30 healthy children subjected to elective "1-day" surgery. The children's age ranged from 6 to 18 years. The examinations were performed in FACScan flow cytometer with the use of wide set of monoclonal antibodies: CD3, CD4, CD8, TCRalphabeta, TCRgammadelta, CD19, CD25, CD45RA, CD45RO, CD69, HLA-DR, CD16 and CD56, which particularly allowed detailed analysis of T lymphocytes. The results showed that most parameters in children 1 year after ALL treatment completion were similar to healthy children. However, we observed persistently low CD4+ T cell numbers, both CD45RA+ as well as CD45RO+ subsets as compared to the control group. This might reflect decreased regenerative potential of immunological system in children 1 year after ALL treatment.


Syntheses of potent Leu-enkephalin analogs possessing beta-hydroxy-alpha,alpha-disubstituted-alpha-amino acid and their characterization to opioid receptors.
Novel Leu-enkephalin (Leu-Enk) (1) analogs possessing various types of alpha-substituted serine instead of its glycine residue in the position 2 were synthesized via an efficient O,N-migration method. The binding characteristics of the synthetic analogs using Chinese hamster ovary (CHO) cells expressed cloned rat mu-, delta-, and kappa-receptors revealed that [(1R,2S)-Ahh2]Enk (7) was the most potent agonist of delta-opioid receptors among all the synthetic analogs tested, and was 10 times more potent than the native Leu-Enk.


Risk multipliers for severe food anaphylaxis.
Anaphylaxis is a severe, life threatening allergic reaction. In most fatal cases of food anaphylaxis, the fatality is not due merely to a simple, linear relationship between the allergen and exposure in a sensitized individual. Compounding factors such as the allergic disease burden-particularly the presence of asthma; comprehension of the potential severity of an event, training in the appropriate use of epinephrine, and emerging metabolic factors should be considered when assessing risk and establishing management strategies. This paper reviews the factors that contribute to the risk of severe anaphylactic events and provides a framework for the ongoing management of patients at risk of severe food allergy.


Maternal plasma proteomics in a rat model of pregnancy complications reveals immune and pro-coagulant gene pathway activation.
The Brown Norway (BN) rat is a model of T-helper 2 immune diseases, and also a model of pregnancy disorders that include placental insufficiency, fetal loss, and pre-eclampsia-like symptoms. The aim of this study was to investigate the plasma proteomic/cytokine profile of pregnant BN rats in comparison to that of the Lewis (LEW) rat strain. Plasma proteomics differences were studied at day 13 of pregnancy in pooled plasma samples by differential in-gel electrophoresis, and protein identification was performed by mass spectrometry. Key protein findings and predicted cytokine differences were validated by ELISA using plasma from rats at various pregnancy stages. Proteomics data were used for ingenuity pathway analysis (IPA). In-gel analysis revealed 74 proteins with differential expression between BN and LEW pregnant dams. ELISA studies confirmed increased maternal plasma levels of complement 4, prothrombin, and C-reactive protein in BN compared to LEW pregnancies. LEW pregnancies showed higher maternal plasma levels of transthyretin and haptoglobin than BN pregnancies. Ingenuity pathway analysis revealed that BN pregnancies are characterized by activation of pro-coagulant, reactive oxygen species, and immune-mediated chronic inflammation pathways, and suggested increased interleukin 6 and decreased transforming growth factor-β1 as potential upstream events. Plasma cytokine analysis revealed that pregnant BN dams have a switch from anti- to pro-inflammatory cytokines with the opposite switch observed in pregnant LEW dams. Brown Norway rats show a maternal pro-inflammatory response to pregnancy that likely contributes to the reproductive outcomes observed in this rat strain.


Downregulation of ciRNA-Kat6b in dorsal spinal horn is required for neuropathic pain by regulating Kcnk1 in miRNA-26a-dependent manner.
Nerve injury-induced maladaptive changes in gene expression in the spinal neurons are essential for neuropathic pain genesis. Circular RNAs (ciRNA) are emerging as key regulators of gene expression. Here, we identified a nervous-system-tissues-specific ciRNA-Kat6 with conservation in humans and mice. We aimed to investigate whether and how spinal dorsal horn ciRNA-Kat6b participates in neuropathic pain. Unilateral sciatic nerve chronic constrictive injury (CCI) surgery was used to prepare the neuropathic pain model. The differentially expressed ciRNAs were obtained by RNA-Sequencing. The identification of nervous-system-tissues specificity of ciRNA-Kat6b and the measurement of ciRNA-Kat6b and microRNA-26a (miRNA-26a) expression level were carried out by quantitative RT-PCR. The ciRNA-Kat6b that targets miRNA-26a and miRNA-26a that targets Kcnk1 were predicted by bioinformatics analysis and verified by in vitro luciferase reports test and in vivo experiments including Western-blot, immunofluorescence, and RNA-RNA immunoprecipitation. The correlation between neuropathic pain and ciRNA-Kat6b, miRNA-26a, or Kcnk1 was examined by the hypersensitivity response to heat and mechanical stimulus. Peripheral nerve injury downregulated ciRNA-Kat6b in the dorsal spinal horn of male mice. Rescuing this downregulation blocked nerve injury-induced increase of miRNA-26a, reversed the miRNA-26a-triggered decrease of potassium channel Kcnk1, a key neuropathic pain player, in the dorsal horn, and alleviates CCI-induced pain hypersensitivities. On the contrary, mimicking this downregulation increased the miRNA-26a level and decreased Kcnk1 in the spinal cord, resulting in neuropathic pain-like syndrome in naïve mice. Mechanistically, the downregulation of ciRNA-Kat6b reduced the accounts of miRNA-26a binding to ciRNA-Kat6b, and elevated the binding accounts of miRNA-26a to the 3' untranslated region of Kcnk1 mRNA and degeneration of Kcnk1 mRNA, triggering in the reduction of KCNK1 protein in the dorsal horn of neuropathic pain mice. The ciRNA-Kat6b/miRNA-26a/Kcnk1 pathway in dorsal horn neurons regulates the development and maintenance of neuropathic pain, ciRNA-Kat6b may be a potential new target for analgesic and treatment strategies.


Circulating intercellular adhesion molecule 1 (ICAM-1), E-selectin and vascular cell adhesion molecule 1 (VCAM-1) in head and neck cancer.
The sera from patients with nasopharyngeal carcinoma (n = 30), oral carcinoma (n = 22) and laryngeal carcinoma (n = 22) was extracted before treatment. The concentration of circulating intercellular adhesion molecule 1 (ICAM-1), E-selectin and vascular cell adhesion molecule 1 (VCAM-1) was measured by enzyme-linked immunoassay and compared with those from normal subjects (n = 20). The concentration of circulating ICAM-1, E-selectin and VCAM-1 was significantly increased in nasopharyngeal carcinoma. Correspondingly, VCAM-1 and E-selectin were significantly increased in laryngeal carcinoma, whereas only E-selectin was elevated in oral carcinoma. The concentrations of these adhesion molecules did not significantly differ with respect to the early and late stages of these carcinomas. Elevated levels of soluble adhesion molecules in the sera of cancer patients at three different head and neck regions, although appearing to be implicated in these tumour formations, may be unrelated to tumour progression.


Supplementation of green tea extract (GTE) in extender improves structural and functional characteristics, total antioxidant capacity and in vivo fertility of buffalo (Bubalus bubalis) bull spermatozoa.
The aim of this study was to elucidate the beneficial effects of green tea extract (GTE) in tris citric acid extender on post thaw structural and functional characteristics, DNA fragmentation (%), total antioxidant capacity (TAC, μM/L), lipid peroxidation (LPO, μM/mL) levels and in vivo fertility of buffalo (Bubalus bubalis) bull spermatozoa. GTE is a acknowledged natural antioxidant, act as a free radical scavenger and protects spermatozoa against oxidative stress. Three mature and donor buffalo bulls were used in this experiment. Two ejaculates were collected per bull on each collection day, followed by initial evaluation for consistency (colour), volume (mL), progressive motility and concentration (x109) and were diluted in five extenders @ 50 x 106/ mL (C = control, no GTE; T1 = treatment 1, GTE 0.1%; T2 = treatment 2, GTE 0.5%; T3 = treatment 3, GTE 0.75% and T4 = treatment 4, GTE1.0%). The experiment was repeated thrice. Data analysis showed that sperm progressive motility (%), plasma membrane integrity (%), supravital plasma membrane integrity (%), viable sperm with intact acrosome (%) and TAC were significantly higher (P < 0.05) in extender supplemented with T4 as compared to control. Furthermore, sperm DNA fragmentation and occurrance of LPO in buffalo bull spermatozoa were significantly lowered in T4 than control. In vitro longevity (%) of spermatozoa was significantly higher in T4 compared to control during 45 and 90 min of incubation at 37 °C. In vivo fertility rate of buffalo bull spermatozoa was significantly higher in T4 compared to control (64.96 vs. 48.40%, P < 0.05). It is concluded that supplementation of tris citric acid extender with 1.0% GTE improved structural and functional characteristics, TAC, in vitro longevity (%) and in vivo fertility, whereas decreased DNA fragmentation and LPO occurrence in buffalo bull spermatozoa after freezing and thawing protocol.


Improved health-related quality of life following a randomized controlled trial of alefacept treatment in patients with chronic plaque psoriasis.
Psoriasis has a negative impact on patients' quality of life. Treatment strategies should address both the cutaneous manifestations of the disease and their impact on quality of life. To evaluate the effect of alefacept on quality of life in 553 patients with chronic plaque psoriasis. In this multicentre, double-blind, parallel-groups study, patients were randomized to receive alefacept for two courses, alefacept in course 1 and placebo in course 2, or placebo in course 1 and alefacept in course 2. In each course, alefacept 7.5 mg or placebo was administered once weekly by 30-s intravenous injection for 12 weeks followed by 12 weeks of observation. The Dermatology Life Quality Index (DLQI), Dermatology Quality of Life Scales (DQOLS) and Short Form-36 Health Survey (SF-36) were administered at baseline, 2 weeks after the last dose in both courses, at the beginning of course 2, and at the end of the observation period in both courses. In course 1, alefacept significantly reduced (improved) mean DLQI scores compared with placebo: 4.4 vs. 1.8 at 2 weeks after the last dose (P<0.0001) and 3.4 vs. 1.4 at 12 weeks after the last dose (P<0.001). Patients who received two courses of alefacept experienced additional enhancement of quality of life measures during the second course. Similar results were observed for the DQOLS. The SF-36 survey confirmed that alefacept had no negative impact on general quality of life. Alefacept improved quality of life in patients with chronic plaque psoriasis and maintained this benefit for at least 12 weeks following cessation of treatment. A second course of alefacept provided additional quality of life benefit.


Laparoscopic transhiatal esophago-gastrectomy after corrosive injury.
Esophago-gastric necrosis is a surgical emergency associated with high morbidity and mortality. We report a laparoscopic transhiatal esophago-gastrectomy performed on a 43-year-old male, presenting two hours after hydrochloric acid ingestion. A gastroscopy showed several oral mucosal ulcers, a significant edema of the pharynx and larynx, a necrosis of the middle and lower esophagus and of the gastric fundus and antrum. A conservative strategy with intensive care observation was initially followed. After a change of clinical signs, chest-abdominal computed tomography was realized and a pneumoperitoneum with free fluid in the left subphrenic space and bilateral pleural effusions was in evidence. A laparoscopic exploration was proposed to the patient, and confirmed the presence of free peritoneal fluid and necrosis with perforation of the upper part of the stomach. A laparoscopic total gastrectomy with subtotal esophagectomy was performed; the procedure finished with an esophagostomy on the left side of the neck and a laparoscopic feeding jejunostomy (video). Total operative time was 235 minutes. After six months a digestive reconstruction with esophagocoloplasty by laparotomy and cervicotomy was easily realized thanks to the advantages (few adhesions, bloodless, and simple colic mobilization) of the previous minimally invasive surgery.


Osmoregulatory profiles and gill histological changes in Nile tilapia (Oreochromis niloticus) exposed to lambda-cyhalothrin.
Lambda-cyhalothrin is a synthetic pyrethroid that mimics the structure and insecticidal properties of pyrethrin, a natural insecticide derived from chrysanthemums. In fish, it disrupts the nervous system, causing motor paralysis and several other alterations associated with varying levels of mortality. This study aimed to evaluate osmoregulatory responses and histological changes in the gills of Oreochromis niloticus chronically exposed to a sublethal dosage (0.86 μg/L) of lambda-cyhalothrin. The mean serum values for Na2+, K+, Cl-, Ca2+, pH, lactate, H+, HCO3, and glucose along to degree of tissue change (DTC) at 24, 96, 168, and 240 h post-exposure (hpe) were evaluated. Lambda-cyhalothrin affected the neuronal motor function at 24 hpe, followed by the increase of the K+, Ca2+, H+, and glucose levels in the exposed group, compared to the control group. Lactate and H+ levels in the exposed group were higher than those in the control group at 168 and 240 hpe respectively. HCO3, and Cl- levels increased at 240 hpe, although there was no change in the pH values. DTC was higher in treated fish than in control fish, but there were no significant differences among time-exposure. The changes detected ranged from hyperemia of the branchial vasculature, eosinophilic granulocytic cell infiltration, mucous cell hyperplasia, and partial fusion of secondary lamellae at 24 hpe to vascular aneurysm formation, and necrosis of the lamellar epithelium at 240 hpe. Thus, a sublethal dosage of lambda-cyhalothrin in the long-term is toxic for Nile tilapia, characterized by hypokalemia, hypercalcemia, hyperglycemia, and respiratory alkalosis, followed by time-dependent histological changes.


A Comparison of Trap Types for Assessing Diversity of Scarabaeoidea on South Carolina Golf Courses.
A 2-yr survey was conducted on golf courses in South Carolina to 1) document the species richness and seasonal activity of Scarabaeoidea; 2) assess any species compositional differences among three trap types (ultraviolet light, unbaited flight-intercept, and unbaited pitfall); and 3) identify any dominant taxa in each trap type. A total of 74,326 scarabaeoid beetles were captured, of which 77.4% were Aphodiinae (not identified to species). The remaining specimens belong to 104 species in 47 genera and 6 families. The most abundant species were Cyclocephala lurida Bland, Dyscinetus morator (F.), Euetheola humilis (Burmeister), Hybosorus illigeri Reiche, and Maladera castanea (Arrow). In all trap types, >90% of all specimens and taxa were collected between April and August. Ultraviolet light traps collected ∼94% of total specimens consisting of 83 taxa (of which 51 were unique to this trap type), whereas flight-intercept traps captured ∼2% of all specimens representing 53 taxa (18 of which were unique), and pitfall traps captured ∼4% of all specimens representing 15 taxa (no unique species; all species also captured by ultraviolet light traps). Indicator species analysis identified 2-3 and 10-13 taxa that were most frequently collected by flight-intercept and ultraviolet light traps, respectively. Flight-intercept traps complemented ultraviolet light traps by capturing more species of dung and carrion beetles and diurnal phytophagous scarab beetles. Results suggested that a similar survey for domestic or exotic scarabaeoid beetles in turfgrass systems should be conducted between April and August using ultraviolet light and flight-intercept traps at 13-58 sites.


[Innate immunity primary immunodeficiencies and infections].
The diagnosis of primary immunodeficiency diseases (PIDs) is important for the early and adaptive care of patients and their families. Among the various known PIDs, a number of them concern the innate immune system, which involve a set of cells and mechanisms involved in the host defense by a nonspecific and fast response. The majority of patients with innate immunity defects have a predisposition to one isolated type of infection (bacterial, viral, or fungal), dependent on the genetic defect involved. This article describes the different PIDs involving innate immunity and the immunological investigations allowing for their diagnosis.


In situ disinfection of sewage contaminated shallow groundwater: a feasibility study.
Sewage-contaminated shallow groundwater is a potential cause of beach closures and water quality impairment in marine coastal communities. In this study we set out to evaluate the feasibility of several strategies for disinfecting sewage-contaminated shallow groundwater before it reaches the coastline. The disinfection rates of Escherichia coli (EC) and enterococci bacteria (ENT) were measured in mixtures of raw sewage and brackish shallow groundwater collected from a coastal community in southern California. Different disinfection strategies were explored, ranging from benign (aeration alone, and aeration with addition of brine) to aggressive (chemical disinfectants peracetic acid (PAA) or peroxymonosulfate (Oxone)). Aeration alone and aeration with brine did not significantly reduce the concentration of EC and ENT after 6 h of exposure, while 4-5 mg L(-1) of PAA or Oxone achieved >3 log reduction after 15 min of exposure. Oxone disinfection was more rapid at higher salinities, most likely due to the formation of secondary oxidants (e.g., bromine and chlorine) that make this disinfectant inappropriate for marine applications. Using a Lagrangian modeling framework, we identify several factors that could influence the performance of in-situ disinfection with PAA, including the potential for bacterial regrowth, and the non-linear dependence of disinfection rate upon the residence time of water in the shallow groundwater. The data and analysis presented in this paper provide a framework for evaluating the feasibility of in-situ disinfection of shallow groundwater, and elucidate several topics that warrant further investigation.


Dynamic CT of solitary pulmonary nodules: comparison of contrast medium distribution characteristic of malignant and benign lesions.
To prospectively assess the role of the dynamic contrast-enhanced CT enhancement characteristics in distinguishing malignant form of benign solitary pulmonary nodules. The study included 87 patients (59 men, 28 women; median age, 59 years) with 87 solitary pulmonary nodules. In all cases, dynamic CT images were obtained before and 20, 30, 45, 60, 75, 90, 120 s, 3, 5, 9, 12, 15 and 20 min after injection of contrast medium. Peak enhancement attenuation value, net enhancement attenuation value, the slope of enhancement, enhancement ratio, outflow of contrast medium (washout), washout ratio and the slope of washout ratio were assessed. Statistical analyses were performed with the Mann-Whitney test, χ(2) test, and receiver-operating characteristic curves. There were 52 malignant and 35 benign nodules. There were no significant differences in net enhancement value, enhancement ratio and the slope of enhancement ratio between malignant and benign nodules (P > 0.05). Malignant nodules showed smaller outflow of contrast medium than did benign nodules. With 12.4HU or lower washout as a cutoff value, the sensitivity and specificity for malignancy were 52.5 and 65.0 %, respectively. With 18.9 % or lower washout ratio as a cutoff value, sensitivity and specificity for malignancy were 60.0 and 75.0 %, respectively. With 0.0180 %/s or lower slope of washout ratio as a cutoff value, sensitivity and specificity for malignancy were 60.0 and 80.0 %, respectively. Dynamic contrast-enhanced CT is helpful in differentiating malignant from benign solitary pulmonary nodules. Smaller washout of contrast enhancement is a predictor that a lesion is malignant.


MALT1 is not alone after all: identification of novel paracaspases.
Paracaspases and metacaspases are two families of caspase-like proteins identified in 2000. Up until now paracaspases were considered a single gene family with one known non-metazoan paracaspase in the slime mold Dictyostelium and a single animal paracaspase called MALT1. Human MALT1 is a critical signaling component in many innate and adaptive immunity pathways that drive inflammation, and when it is overly active, it can also cause certain forms of cancer. Here, we report the identification and functional analysis of two new vertebrate paracaspases, PCASP2 and PCASP3. Functional characterization indicates that both scaffold and protease functions are conserved across the three vertebrate paralogs. This redundancy might explain the loss of two of the paralogs in mammals and one in Xenopus. Several of the vertebrate paracaspases currently have incorrect or ambiguous annotations. We propose to annotate them accordingly as PCASP1, PCASP2, and PCASP3 similar to the caspase gene nomenclature. A comprehensive search in other metazoans and in non-metazoan species identified additional new paracaspases. We also discovered the first animal metacaspase in the sponge Amphimedon. Comparative analysis of the active site suggests that paracaspases constitute one of the several subclasses of metacaspases that have evolved several times independently.


Dry spinal tap during real-time ultrasound-guided paramedian spinal injection with patient in the lateral decubitus position: A single-centre retrospective study.
Real-time ultrasound-guided (USG) spinal injection is generally performed via the paramedian sagittal oblique (PMSO) ultrasound window. The aim of this retrospective study was to draw attention to the occurrence of 'dry tap' during real-time USG spinal injection. Single-centre retrospective study. University teaching hospital, Hong Kong, China. Data from 113 patients (aged 69.2 ± 18.0 years and BMI 22.3 ± 3.6 kg m-2) of American Society of Anesthesiologists physical status 1 to 3 scheduled for surgery under neuraxial blockade between 2007 to 2017 were reviewed. Real-time USG spinal injections or combined spinal-epidural (CSE) using the PMSO ultrasound window with the patient in the lateral decubitus position and the spinal needle inserted from the nondependent side were studied. 'Dry tap' was defined as a failure of cerebrospinal fluid (CSF) to efflux from the hub of the needle, within 3 min, with the spinal needle visualised sonographically within the thecal sac. 'Slow CSF efflux' was defined as efflux of CSF within 1 to 3 min. Irrespective of whether it was a 'dry tap' or 'slow CSF efflux', the planned dose of local anaesthetic was injected through the spinal needle. The combined incidence of 'dry tap' and 'slow CSF efflux' was 23.8% (27/113) with an individual incidence for each event of 9.7% (11/113) and 14.2% (16/113), respectively. Under the conditions of this study, successful spinal anaesthesia developed in all patients. 'Dry tap' occurs in 9.7% of cases during real-time USG spinal injection using the PMSO ultrasound window, with the patient in the lateral decubitus position and the spinal needle inserted from the nondependent side. ChiCTR-IOR-1800019011, Chinese Clinical Trials Registry (www.chictr.org.cn).


Hemodynamic and antihypertensive effects of captopril, an orally active angiotensin converting enzyme inhibitor.
Captopril inhibits angiotensin II formation and bradykinin degradation in vivo. Eleven patients with essential hypertension (EH) and four patients with renovascular hypertension (RVH) were treated with captopril for periods ranging from 3 days to 12 months. All patients had a diastolic blood pressure (DBP) over 95 mm Hg after receiving a placebo for 3 days. Captopril given in ascending doses (10-1000 mg/day) caused normalization of blood pressure in all but three patients, one with severe RVH whose pressure fell 11%, one patient with severe EH, whose pressure fell 27%, and one with EH whose blood pressure fell 8.5%. The average control DBP in patients with EH was 113.7 +/- 5.5 (SE) mm Hg and fell to 89.9 +/- 3.6 mm Hg (p less than 0.001), while DBP in patients with RVH fell from 110.7 +/- 7.6 mm Hg to 94.5 +/- 8.2 (p less than 0.005). All patients were studied in balance on a 100 mEq sodium (Na) diet. Plasma renin activity (PRA) versus 24-hour urinary Na excretion increased sevenfold during therapy while converting enzyme activity fell by about one half. The magnitude of the blood pressure response was not related to control PRA. Cardiac output was estimated by echocardiography during placebo administration and during maintenance therapy with captopril. A significant change was not observed. Total peripheral resistance fell an average of 18.9% (p less than 0.05) in 11 of the 13 patients in whom the measurement could be made. It is concluded that captopril effectively lowers blood pressure in patients with EH or RHV by reducing total peripheral resistance.


Regulatory T lymphocytes in myocardial infarction: A promising new therapeutic target.
Myocardial infarction (MI) is one of the leading causes of death especially in developed countries. Although the advent of early myocardial reperfusion therapy contributes to decreasing the mortality of patients with MI, cardiac ischemia-reperfusion injury and adverse remodeling during the repair process still remain the major factors impairing cardiac function and resulting in unsatisfactory prognosis. Excessive inflammation and immune responses play a crucial role during the whole process of MI. Regulatory T lymphocytes, characterized by immunosuppressive capacity, are associated with many immune-related diseases. Recent studies have proven a protective role of regulatory T cells in MI, which is mainly achieved by modulating inflammation and immune responses. In this review, we will summarize current knowledge of regulatory T lymphocytes, and highlight their roles in the onset of MI, ischemia-reperfusion injury, as well as post-infarct cardiac healing and remodeling.


Treatment of instent restenosis following stent-supported renal artery angioplasty.
We prospectively studied the long-term outcome of endovascular treatment of instent renal artery stenosis (IRAS). Restenosis is a considerable drawback of stent-supported angioplasty of renal artery stenosis especially in small vessel diameters. The appropriate treatment strategy is not yet defined. During a 10-year period 56 consecutive patients (65 lesions) with their first IRAS were included in a prospective follow-up program (mean follow-up 53 +/- 25 months, range 6-102). Primary endpoint of the study was the reoccurence of IRAS (>or= 70%) after primarily successful treatment of the first IRAS determined by duplex ultrasound. Primary success rate was 100%, no major complication occurred. Nineteen lesions were treated with plain balloon angioplasty (group 1, 30%), 42 lesions with stent-in-stent placement (group 2, 65%) using various bare metal balloon expandable stents, and 4 lesions with drug-eluting stent angioplasty (group 3, 6%). During follow-up, overall 21 lesions (32%) developed reoccurence of IRAS: n = 7/19 in group 1 (37%), n = 14/42 in group 2 (33%), and n = 0/4 in group 3 (0%; P = 0.573). Reoccurence of IRAS was more likely to occur in smaller vessel diameters than in larger ones [3-4mm: 4/7 (57%); 5 mm: 11/26 (42%); 6 mm: 5/25 (20%); 7 mm: 1/7 (14%), P = 0.088]. Multivariable analysis found bilateral IRAS and IRAS of both renal arteries of the same side in case of multiple ipsilateral renal arteries as independent predictors for reoccurence of IRAS. Treatment of IRAS is feasible and safe. The data demonstrate a nonsignificant trend towards lower restenosis with restenting of IRAS versus balloon angioplasty of IRAS. Individual factors influence the likelihood of reoccurence of IRAS.


Characterisation of heavy oils using near-infrared spectroscopy: optimisation of pre-processing methods and variable selection.
In this study, chemometric predictive models were developed from near infrared (NIR) spectra for the quantitative determination of saturates, aromatics, resins and asphaltens (SARA) in heavy petroleum products. Model optimisation was based on adequate pre-processing and/or variable selection. In addition to classical methods, the potential of a genetic algorithm (GA) optimisation, which allows the co-optimisation of pre-processing methods and variable selection, was evaluated. The prediction results obtained with the different models were compared and decision regarding their statistical significance was taken applying a randomization t-test. Finally, the results obtained for the root mean square errors of prediction (and the corresponding concentration range) expressed in %(w/w), are 1.51 (14.1-99.1) for saturates, 1.59 (0.7-61.1) for aromatics, 0.77 (0-34.5) for resins and 1.26 (0-14.7) for asphaltens. In addition, the usefulness of the proposed optimisation method for global interpretation is shown, in accordance with the known chemical composition of SARA fractions.


CSF biomarkers for Alzheimer's disease: use in early diagnosis and evaluation of drug treatment.
Early diagnosis of Alzheimer's disease is important in initiating symptomatic treatment with acetylcholine esterase inhibitors, and will be of even greater significance if drugs with a potential to slow down the degenerative process, such as beta-secretase inhibitors and beta-amyloid vaccination, prove to have a clinical effect. During the last decade, research efforts have focused on developing cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease. In this review, the background and principles for, and the diagnostic performance of, the CSF biomarkers total tau, phosphorylated tau and the 42-amino acid form of beta-amyloid, are reviewed. New candidate CSF biomarkers and new strategies, including multiparameter immunoassays and CSF proteomics techniques, in the search of additional CSF biomarkers are also reviewed. Finally, the rationale for the use of CSF biomarkers to identify and monitor the biochemical effect of new drug candidates is reviewed.


Short- and Long-Term Prognostic Implications of Jugular Venous Distension in Patients Hospitalized With Acute Heart Failure.
The present study was designed to assess the role of jugular venous distension (JVD) as a predictor of short- and long-term mortality in a "real-life" setting. The independent association between the presence of admission JVD and the 30-day, 1- and 10-year mortality was assessed among 2,212 patients hospitalized with acute heart failure (HF) who were enrolled in the Heart Failure Survey in Israel (2003). Independent predictors of JVD finding in study patients included: the presence of significant hyponatremia (odds ratio [OR] 1.48; p = 0.03), reduced left ventricular ejection fraction ([LVEF] OR 1.24; p = 0.03), anemia (OR 1.3; p = 0.01), New York Heart Association III to IV (OR 1.34; p <0.01) and age >75 years (OR 1.32; p = 0.01). The presence of JVD versus its absence at the time of HF hospitalization was associated with increased 30-day mortality (7.2% vs 4.9%, respectively; p = 0.02), 1-year (33% vs 28%, respectively; p <0.001), and greater 10-year mortality (91.8% vs 87.2%, respectively; p <0.001). Consistently, interaction term analysis demonstrated that the presence of JVD at the time of the index HF hospitalization was independently associated with a significant increased risk for 10-year mortality, with a more pronounced effect among younger patients, patients with reduced LVEF, preserved renal function, and chronic HF. In conclusion, in patients admitted with HF, JVD is associated with specific risk factors and is independently associated with increased risk of both short- and long-term mortality. These findings can be used for improved risk assessment and management of this high-risk population.


Preferential use of carbon central metabolism and anaerobic respiratory chains in porcine extraintestinal pathogenic Escherichia coli during bloodstream infection.
Porcine extraintestinal pathogenic Escherichia coli (ExPEC) is occurring with increasing frequency in China, and leads to significant economic and welfare costs in the swine industry. The underlying mechanisms of porcine ExPEC in blood colonization during systematic infection is poorly understood. Here we measured the gene expression of porcine ExPEC in infected animal bloodstream in vivo and fresh swine blood in vitro. Using comparisons with P values of ≤ 0.01, we identified 354 and 313 genes as being significantly up- or down-regulated at least 2-fold change during bloodstream infection, respectively. Excepting for an array of iron acquisition systems, numerous genes involved in carbon central metabolism and anaerobic respiratory chains were upregulated here. These genes were categorized into several clusters including the TCA-cycle (frdABCD, citCEFXG), d-ribose transporter (rbsDACB), nickel transporter (nikABCDER), NiFe hydrogenase (hybOABCDEF, hycBCDEFG), Hyp-complex (hypABCDE), DMSO reductase (dmsABC and ynfEFGHI), format dehydrogenase (fdnGHI) and NADH dehydrogenase I (nuoA-N). The mutant with simultaneous inactivation of ribose and citrate imports showed significant reduced fitness in host blood, suggesting these two carbohydrates are utilized by central metabolism network as important carbon-source during bloodstream infection. Similar deficiency was also observed in the mutant double deleted NiFe hydrogenase 2 and 3 anaerobic respiratory chains. Further study found that FNR (a global regulator facilitating bacterial adaptation to anaerobic conditions) is an important regulator in response to bloodstream to activate center metabolism and anaerobic respiratory chains, thus contribute to the full-virulence of porcine ExPEC. These findings provide compelling evidence to support the notion that carbon central metabolism network and anaerobic respiratory chains play key roles for porcine ExPEC fitness within host bloodstream.


A case of autoimmune gastritis with fundic gland polyp-like pseudopolyps presenting with nodular enterochromaffin-like cell hyperplasia.
Pseudopolyps, a type of remnant oxyntic mucosa on a background of corpus-restricted mucosal atrophy, are a characteristic endoscopic finding in autoimmune gastritis (AIG). Linear or nodular enterochromaffin-like (ECL) cell hyperplasia, a characteristic histopathological finding of AIG, is not generally found in pseudopolyps. We report a case of AIG with fundic gland polyp (FGP)-like pseudopolyps containing nodular ECL cell hyperplasia. A 64-year-old man underwent esophagogastroduodenoscopy, which revealed atrophic changes limited to the corpus, with a normal antrum. The greater curvature was less atrophic than the lesser curvature. Sessile or semipedunculated polypoid lesions were observed on the greater curvature and on the anterior and posterior walls of the corpus. The polypoid lesions resembled FGPs, although some were larger than FGPs generally are. Histologically, non-atrophic fundic glands with parietal cell pseudohypertrophy were observed in the upper regions of the polypoid lesions. By contrast, at the base of the lesions, where linear and nodular ECL cell hyperplasia was identified by immunohistochemical staining, destruction of fundic glands with lymphocytic infiltration, loss of parietal cells, and pseudopyloric metaplasia was observed. Anti-parietal cell antibody positivity and hypergastrinemia confirmed the diagnosis of AIG with pseudopolyps. FGP-like pseudopolyps can, therefore, be present with nodular ECL cell hyperplasia in AIG.


A large and late mediastinal metastasis from a uterine smooth muscle tumour of uncertain malignant potential: A case report.
Smooth muscle tumours of uncertain malignant potential (STUMP) are mesenchymal uterine tumours with a malignant potential found somewhere between that of benign leiomyomas and leiomyosarcomas. Only three cases of STUMP pulmonary metastasis exist in the literature. We report the case of a 63 year-old female patient presenting with dysphonia secondary to recurrent laryngeal nerve paralysis due to an enormous mediastinal STUMP metastasis, 14 years after having undergone a total hysterectomy with bilateral salpingo-oophorectomy. A successful left pneumonectomy was performed and the mass weighing 1570 g was histologically confirmed as a STUMP metastasis. Only three cases of pulmonary metastasis from STUMP have been reported in the recent literature and no robust information exists about the metastatic nature of STUMP. No cases exist in the literature of a successful pneumonectomy performed for a STUMP metastasis of such large dimensions presenting after many years from the diagnosis of the primary uterine lesion. Physicians should keep in mind that the finding of a smooth muscle tumour in the lung of a woman should promptly raise the suspicion of a metastatic uterine malignancy, even several years after diagnosis of the primary lesion. Despite the size, invasiveness and late presentation of the STUMP metastasis, the surgery was successful and the patient no longer requires oxygen therapy.


Biliary anastomosis and biliary complications following living donor liver transplantation.
Biliary complications are one of the most important problems in liver transplantation. Regardless of various improvements of surgical technique, liver transplantation is associated with significant biliary problems. In this article, we have described a biliary anastomosis method with a continuous suture (CS) technique in the posterior wall and interrupted suture (IS) technique for the anterior wall. We performed this biliary reconstruction in 28 adult patients between September 2003 and August 2007. Prior to that time our procedure was a CS anastomosis for both the anterior and posterior walls. A 5-Fr catheter is inserted into the biliary system. The current biliary complication was 3 cases (13.0%) of stenosis at the anastomosis, which is lower than that for a CS anastomosis. This anastomosis reduced biliary complications and is simple.


Recombination of carbon monoxide with hemoglobin after flash photolysis of the carboxyderivative in mixed solvents at subzero temperature.
The kinetics of recombination of carbon monoxide to hemoglobin produced by total flash photolysis of its carboxyderivative are studied at low temperatures (down to --55 degrees C) in mixed hydroalcoholic solvents. The rates are found to be different in two solvents used, namely ethylene glycol/buffer and methanol/buffer; for the former, the rates at subzero temperatures are simply explained by cooling and are consistent with the activation energy as measured in aqueous solution, while those in methanol/buffer show evidence of a specific solvent effect. Values are reported for the rate constants and activation energies in the two solvents.


A comparative analysis of root surface biomodification with ethylene diamine tetra acetic acid and tetracycline hydrochloride: An in vitro scanning electron microscopic study.
The outcome of periodontal regenerative therapy depends upon the of the biocompatibility root surfaces to the regenerating periodontal tissues. This in vitro scanning electron microscopic (SEM) study was designed to evaluate and compare the demineralizing efficacy of ethylene diamine tetra acetic acid (EDTA), with that of tetracycline hydrochloride applied on to the mechanically treated root surfaces of periodontally involved tooth. Forty specimens were prepared from teeth extracted due to advanced periodontal disease and divided into two groups. The study group was treated with an EDTA solution (pH 7.4) and the control group was treated with a tetracycline hydrochloride solution (pH 1.8). The photomicrographs obtained were assessed for presence of smear layer, number of exposed dentinal tubules, area occupied by tubule orifices along with intertubular surface appearance. The results thus obtained were analyzed statistically. Both EDTA and tetracycline were effective in removing the smear layer and the exposure of the number of dentinal tubules. The diameters of the tubules and thereby the surface area occupied by the tubule orifices in the EDTA treated group were significantly greater than the tetracycline HCL treated group (p < 0.05). The EDTA produced better effects than tetracycline by providing more demineralized area and collagen exposure at a neutral pH.


Arthroscopic Treatment of Osseous Instability of the Shoulder.
Bony deficiency of the anteroinferior glenoid rim as a result of a dislocation can lead to recurrent glenohumeral instability. These lesions, traditionally treated by open techniques, are increasingly being treated arthroscopically as our understanding of the pathophysiology and anatomy of the glenohumeral joint becomes clearer. Different techniques for arthroscopic management have been described and continue to evolve. While the success of the repair is surgeon dependent, the recent advances in arthroscopic shoulder surgery have contributed to the growing acceptance of arthroscopic reconstruction of glenoid bone defects to restore stability. The purpose of this study was to describe arthroscopic surgical management options for patients with glenohumeral osseous lesions and instability. A comprehensive search of PubMed, Cochrane, and Medline was conducted to identify eligible studies. The reference lists of identified articles were then screened. Both technique articles and long-term outcome studies evaluating arthroscopic management of glenohumeral lesions were included. Studies included for final analysis ranged from Level II to V evidence. Technique articles include suture anchor fixation of associated glenoid rim fractures, arthroscopic reduction and percutaneous fixation of greater tuberosity fractures, arthroscopic filling ("remplissage") of the humeral Hill-Sachs lesion, and an all-arthroscopic Latarjet procedure. The overall redislocation rate varied but was consistently <10% with a low complication rate. Management of glenohumeral instability can be challenging but more recent advances in arthroscopic techniques have provided improved means of treating this diagnosis. This manuscript provides a comprehensive review of the arthroscopic treatment of osseous instability of the shoulder. It provides an in depth look at the various treatment options and describes techniques for each.


Removal of micropollutants in drinking water using UV-LED/chlorine advanced oxidation process followed by activated carbon adsorption.
This study investigated the removal of three selected micropollutants (i.e., bisphenol A, diclofenac and caffeine) in drinking water using the UV-LED/chlorine advanced oxidation process (AOP) followed by activated carbon adsorption. The degradation of bisphenol A, diclofenac and caffeine was predominantly contributed by chlorination (>60%), direct UV photolysis (>80%) and radical oxidation (>90%), respectively, during the treatment by the UV-LED/chlorine AOP at three tested UV wavelengths (i.e., 265, 285 and 300 nm). The most effective UV wavelengths for the degradation of bisphenol A, diclofenac and caffeine were 265, 285 and 300 nm, respectively. The degradation of all the three micropollutants was enhanced with increasing pH from 6 to 8, though the reasons for the pH dependence were different. The residues of the micropollutants and their degradation (by)products were removed by post-adsorption using granular activated carbon (GAC). Interestingly and more importantly, the adsorption rates of the degradation (by)products were 2-3 times higher than the adsorption rates of the corresponding micropollutants, indicating the formation of more adsorbable (by)products after the AOP pre-treatment. The UV-LED/chlorine AOP followed by GAC adsorption provides a multi-barrier treatment system for enhancing micropollutant removal in potable water. The findings also suggest the merit of the sequential use of UV-LEDs followed by GAC in treating chlorine-containing potable water in small-scale water treatment systems (e.g., point-of-use or point-of-entry water purifiers).


Sex and age differences in clinically significant symptoms of depression and anxiety among people in Australia in the first month of COVID-19 restrictions: a national survey.
To identify sex and age differences in clinically significant symptoms of depression and anxiety and the factors associated with these differences among adults in Australia during COVID-19-related restrictions. Anonymous online survey. Australia. Adults aged over 18 years living in Australia were eligible and 13 829 contributed complete data. Of these, 13 762 identified as female (10 434) or male (3328) and were included in analyses. None. Clinically significant symptoms of depression (≥10 on Patient Health Questionnaire 9) or anxiety (≥10 on Generalized Anxiety Disorder Scale 7 (GAD-7)), and experiences of irritability (GAD-7 item 6). Women were more likely than men to have clinically significant symptoms of depression (26.3% (95% CI 25.4 to 27.1) vs 20.1% (95% CI 18.7 to 21.5), p<0.001) and anxiety (21.8% (95% CI 21.0 to 22.6) vs 14.2% (95% CI 13.0 to 15.4), p<0.001) and to have experienced irritability in the previous fortnight (63.1% (95% CI 62.1 to 64.0) vs 51.4% (95% CI 49.7 to 53.2), p<0.001). They were also more likely than men to be doing unpaid work caring for children (22.8% (95% CI 22.0 to 23.6) vs 8.6% (95% CI 7.7 to 9.6), p<0.001) and dependent relatives (9.8% (95% CI 9.2 to 10.3) vs 5.7% (95% CI 4.9 to 6.5), p<0.001) which made significant contributions to the mental health outcomes of interest. Loss of employment, fear of contracting COVID-19 and feeling a severe impact of the restrictions were associated with poorer mental health in women and men of all ages. Rates of clinically significant symptoms of depression and anxiety were higher among women than men. Rather than being intrinsically more vulnerable to mental health problems during the COVID-19 pandemic, the higher risk of symptoms of anxiety and depression among women may in part be explained by their disproportionate burden of unpaid caregiving.


An association between primary biliary cirrhosis and jejunal villous atrophy resembling celiac disease.
A 76-year-old female presented with malabsorption and was subsequently shown to have jejunal villous atrophy. There was only partial clinical and histologic recovery with gluten withdrawal, but this was thought to be due to poor adherence to the diet. The findings were considered to be consistent with adult celiac disease. During the course of investigations, she was also found to have primary biliary cirrhosis. This is the fifth recorded instance of this association and the first from North America. Because these are uncommon conditions, it is postulated that this is unlikely to be a chance association. The recognition of this coexistence is of practical importance in the investigation and treatment of patients with primary biliary cirrhosis and celiac disease.


Zoonotic diseases and human health: the human influenza example.
Over the past few decades a large number of new and emerging infectious diseases have been recognised in humans, partly because of improved diagnostic technologies and increased awareness and also, partly because of dynamic ecological changes between human hosts and their exposure to animals and the environment (Coker et al. 2011). Some 177 new pathogenic organisms have been recognised to be 'emerging', that is, have newly arisen or been newly introduced into human populations; almost three quarters of these, 130 (73%), have come from zoonotic origins (Cascio et al. 2011; Cutler, Fooks & Van Der Poel 2010; Taylor, Latham & Woolhouse 2001; Woolhouse & Gowtage-Sequeria 2005). One of the most prevalent and important human infectious disease is influenza, a disease responsible globally for a quarter million deaths annually. In the USA alone the toll from influenza is estimated at 36 000 deaths and 226 000 hospitalisations, and it ranks as the most important cause of vaccine preventable mortality in that country (CDC 2010). The epidemiological behaviour of human influenza clearly defines it as an emerging infectious disease and the recent understanding of its zoonotic origins has contributed much to the understanding of its behaviour in humans (Fauci 2006).


Calcium-induced calcium release in smooth muscle: the case for loose coupling.
This article reviews the key experiments demonstrating calcium-induced calcium release (CICR) in smooth muscle and contrasts the biophysical and molecular features of coupling between the sarcolemmal (L-type Ca(2+) channel) and sarcoplasmic reticulum (ryanodine receptor) Ca(2+) channels in smooth and cardiac muscle. Loose coupling refers to the coupling process in smooth muscle in which gating of ryanodine receptors is non-obligate and may occur with a variable delay following opening of the sarcolemmal Ca(2+) channels. These features have been observed in the earliest studies of CICR in smooth muscle and are in marked contrast to cardiac CICR, where a close coupling between T-tubular and SR membranes results in tight coupling between the gating events. The relationship between this "loose coupling" and distinct subcellular release sites within smooth muscle cells, termed frequent discharge sites, is discussed.


Different Approaches in Skull Base Surgery Carry Risks for Different Types of Complications.
Complications are not uncommon in the complex field of skull base surgery. The intrinsic relationship of lesions in this region to important neurovascular structures, dura mater, and bone may lead to significant morbidity and mortality. The evolution of endoscopic endonasal surgery has had a significant impact on this field as a less invasive option for treatment of selected lesions, but major morbidity may still occur; moreover, endoscopic approaches have been associated with higher rates of some specific complications, such as cerebrospinal fluid leaks. Based on a presented case report, the authors discuss the management of various complications associated with different approaches for resection of skull base malignancies, including epidural and intradural pneumocephalus, subdural hematoma, and subdural empyema. Important lessons learned by the senior author throughout more than 30 years of his skull base surgery practice are highlighted. The inherent risk of complications in skull base surgery emphasizes the importance of their avoidance, prevention, and learning from one's unfavorable experience so as not to repeat them.


Addition of cyclosporine/tacrolimus for pediatric relapsed lupus nephritis during mycophenolate mofetil maintenance therapy.
We aimed to evaluate the efficacy of low-dose cyclosporine (CsA) or tacrolimus (Tac) in children with proliferative lupus nephritis (PLN) during maintenance therapy. A low dose of CsA or Tac was added to 11 children who relapsed during mycophenolate mofetil (MMF) maintenance therapy. Renal remission was analyzed at 3 and 6 months, and at 1, 2, and 3 years after CsA/Tac addition. Adverse effects were recorded. The clinical response rates were 81.9%, 100%, 90.0%, 100%, and 100% at 3 months, 6 months, 1 year, 2 years, and 3 years after CsA/Tac addition, respectively. Complete renal remission rates were 45.5%, 45.5%, 40.0%, 44.4%, and 71.4% at 3 months, 6 months, 1 year, 2 years, and 3 years after CsA/Tac addition, respectively. None of the patients had severe adverse events. Low-dose CsA/Tac combined with MMF shows a promising effect in renal remission with acceptable safety in children with PLN. Therefore, this combination would be a good choice for children with lupus nephritis who relapse or have suboptimal MMF maintenance therapy.


H3K27M in Gliomas Causes a One-Step Decrease in H3K27 Methylation and Reduced Spreading within the Constraints of H3K36 Methylation.
The discovery of H3K27M mutations in pediatric gliomas marked a new chapter in cancer epigenomics. Numerous studies have investigated the effect of this mutation on H3K27 trimethylation, but only recently have we started to realize its additional effects on the epigenome. Here, we use isogenic glioma H3K27M+/- cell lines to investigate H3K27 methylation and its interaction with H3K36 and H3K9 modifications. We describe a "step down" effect of H3K27M on the distribution of H3K27 methylation: me3 is reduced to me2, me2 is reduced to me1, whereas H3K36me2/3 delineates the boundaries for the spread of H3K27me marks. We also observe a replacement of H3K27me2/3 silencing by H3K9me3. Using a computational simulation, we explain our observations by reduced effectiveness of PRC2 and constraints imposed on the deposition of H3K27me by antagonistic H3K36 modifications. Our work further elucidates the effects of H3K27M in gliomas as well as the general principles of deposition in H3K27 methylation.


[Variable angle strabismus and its relation to poor vision and psychomotor retardation].
Variable angle strabismus can be inward (esotropy) or outward (exotropy) or vary from esotropy to exotropy. Mental retardation has been found to be related to strabismus in 50% or more of the cases and 35% of these had variable angle strabismus. A total of 61 patients with variable angle strabismus were studied finding 55.7% with esotropy, 36% exotropy and 8.2% varying from esotropy to exotropy. Of those under study, 64% were females and 77% under five years old. No accommodative factors were found in any of the patients. The best results were obtained through surgery (recession plus Faden) previous rehabilitation.


Hypoxia-inducible factor-targeting prodrug TOP3 combined with gemcitabine or TS-1 improves pancreatic cancer survival in an orthotopic model.
Pancreatic cancer is one of the most lethal digestive system cancers with a 5-year survival rate of 4-7%. Despite extensive efforts, recent chemotherapeutic regimens have provided only limited benefits to pancreatic cancer patients. Gemcitabine and TS-1, the current standard-of-care chemotherapeutic drugs for treatment of this severe cancer, have a low response rate. Hypoxia is one of the factors contributing to treatment resistance. Specifically, overexpression of hypoxia-inducible factor, a master transcriptional regulator of cell adaption to hypoxia, is strongly correlated with poor prognosis in many human cancers. TAT-ODD-procaspase-3 (TOP3) is a protein prodrug that is specifically processed and activated in hypoxia-inducible factor-active cells in cancers, leading to cell death. Here, we report combination therapies in which TOP3 was combined with gemcitabine or TS-1. As monotherapy, gemcitabine and TS-1 showed a limited effect on hypoxic and starved pancreatic cancer cells, whereas co-treatment with TOP3 successfully overcame this limitation in vitro. Furthermore, combination therapies of TOP3 with these drugs resulted in a significant improvement in survival of orthotopic pancreatic cancer models involving the human pancreatic cancer cell line SUIT-2. Overall, our study indicates that the combination of TOP3 with current chemotherapeutic drugs can significantly improve treatment outcome, offering a promising new therapeutic option for patients with pancreatic cancer.