Bcl-2 mediated suppression of apoptosis in myeloma NS0 cultures.
The influence of Bcl-2 expression on the suppression of apoptosis during the cultivation of an NS0 cell line expressing a chimeric antibody was investigated. Following selection of transfectants in medium containing G418, Western analysis revealed evidence of some up-regulation of endogenous Bcl-2 expression even in the control vector transfectants. Cultivation of the two cell lines in suspension batch cultures clearly demonstrated the enhanced robustness of the bcl-2 vector transfected cells. Suppression of apoptosis resulted in an approximately 20% increase in maximum viable cell number, and a doubling in culture duration compared to the control transfected cells. However, despite the significant affect on viability, Bcl-2 expression did not result in an increase in final antibody titre in comparison with the control cell line. Exposure of cells to various nutrient limited conditions further emphasised the influence of Bcl-2 on cell survival. After 3 days of exposure to serum, glucose, glutamate and asparagine deprivation, the viable cell number and viability were significantly higher in the bcl-2 transfected cell line. When control cells were deprived of all amino acids, there was a complete loss of viability and viable cell number within 3 days. By contrast, the bcl-2 transfected cell line retained greater than 75% of the initial viable cell number and about 70% viability. In response to exposure to 8 mM thymidine (a cytostatic agent) the control cell line underwent complete loss of viability and viable cell number after 6 days. This compared with 18 days for complete loss of viability in the bcl-2 transfected cell line. As under batch culture conditions, there was no difference between the two cell lines in final antibody titre, which indicated that MAb synthesis is limited by nutrient availability during the latter stages of culture in both cases. When fed batch cultures were carried out using a concentrated essential amino acid feed, the bcl-2 cell line exhibited a 60% increase in maximum viable cell number and a 50% increase in culture duration, when compared to the control cell line. Moreover, the bcl-2 cell line exhibited a greater than 40% increase in maximum antibody titre.


Association between statins and prostate tumor inflammatory infiltrate in men undergoing radical prostatectomy.
Cholesterol-lowering drugs known as statins have been reported to have significant anti-inflammatory properties. Given that inflammation may contribute to prostate cancer progression and that statins may reduce the risk for advanced prostate cancer, we investigated whether statin use was associated with reduced intratumoral inflammation in radical prostatectomy (RP) specimens. Inflammation within index tumors of 236 men undergoing RP from 1996 to 2004 was graded by a single pathologist as grade 0 (absent), 1 (mild: < or =10%), and 2 (marked: >10%). Preoperative statin use was analyzed by grouping subjects as statin users or nonusers. Type and dosage of statin was accounted for using dose equivalents with 20 mg simvastatin as reference. Logistic regression was used to determine the association between statin use and intratumoral inflammation controlling for age, race, body mass index, prostate-specific antigen, year of surgery, clinical stage, pathologic Gleason sum, surgical margin status, extracapsular extension, seminal vesicle invasion, prostate weight, time from prostate biopsy to RP, and nonsteroidal anti-inflammatory drug use. Preoperative statin use was significantly associated with lower risk for any (grade > or =1) intratumoral inflammation (odds ratio, 0.31; 95% confidence interval, 0.10-0.98; P = 0.047) on multivariable analysis, with doses > or =20 mg simvastatin equivalents being more strongly associated (relative to nonuse; odds ratio, 0.22; 95% confidence interval, 0.06-0.79; P = 0.02). In a cohort of men undergoing RP, statin use was associated with significantly lower risk of any inflammation within prostate tumors. Given previous reports that inflammation is associated with advanced prostate cancer, and statin use is associated with decreased prostate cancer progression risk, our findings suggest that inhibition of inflammation within tumors may be a potential mechanism for purported anti-prostate cancer properties of statins.


The application of solid phase extraction to the analysis of tobacco-specific nitrosamines.
A new isolation and separation method has been developed for the alkaloid-related nitrosamines in tobacco, called tobacco-specific nitrosamines (TSNA). The improved isolation procedure involves the extraction by sonication of TSNA from cured tobacco with toluene and an aqueous citrate buffer solution, while purification is achieved by solid phase extraction on small silica cartridges. Interfering extract materials are eluted from the silica cartridges with the toluene and a chloroform-methylene chloride solvent, while subsequent elution with chloroform yields the TSNA in a purified fraction. Gas chromatographic analyses on an SE-54-coated glass capillary column and detection by a nitrogen-phosphorous detector produce very good data on the four TSNAs, which include N-nitrosanatabine (NATB), N-nitrosoanabasine (NAB), 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (called NNK), and N-nitrosonornicotine (NNN). The method is shown to be quantitative, reproducible, and applicable to the determination of TSNA in various tobacco samples, such as stems and lamina of cured tobacco leaves, as well as to smokeless tobacco.


Silent suffering: understanding and treating children with selective mutism.
Children with selective mutism (SM) restrict speech in some social environments, often resulting in substantial academic and social impairment. Although SM is considered rare, one or more children with SM can be found in most elementary schools. Assessment is performed to confirm the diagnosis, rule out psychological and medical factors that may account for the mutism, ascertain comorbid and exacerbating conditions needing treatment, and develop an intervention plan. Interventions are often multidisciplinary and focus on decreasing anxiety, increasing social speech and ameliorating SM-related impairment. Research is limited, but symptomatic improvement has been demonstrated with behavioral interventions and multimodal treatments that include school and family participation, as well as behavioral methods. Selective serotonin-reuptake inhibitors, especially fluoxetine, have also been found to be efficacious and merit consideration in severe cases. Persistence of some SM or anxiety symptoms despite treatment is common. Further development of treatments targeting specific etiological factors, comparative treatment studies and determination of optimal involvement of families and schools in treatment are needed to improve outcomes for children with SM.


Stay Mindful and Carry on: Mindfulness Neutralizes COVID-19 Stressors on Work Engagement via Sleep Duration.
We examine whether mindfulness can neutralize the negative impact of COVID-19 stressors on employees' sleep duration and work engagement. In Study 1, we conducted a field experiment in Wuhan, China during the lockdown between February 20, 2020, and March 2, 2020, in which we induced state mindfulness by randomly assigning participants to either a daily mindfulness practice or a daily mind-wandering practice. Results showed that the sleep duration of participants in the mindfulness condition, compared with the control condition, was less impacted by COVID-19 stressors (i.e., the increase of infections in the community). In Study 2, in a 10-day daily diary study in the United Kingdom between June 8, 2020, and June 19, 2020, we replicate our results from Study 1 using a subjective measure of COVID-19 stressors and a daily measure of state mindfulness. In addition, we find that mindfulness buffers the negative effect of COVID-19 stressors on work engagement mediated by sleep duration. As the COVID-19 pandemic is ongoing and the number of reported cases continues to rise globally, our findings suggest that mindfulness is an evidence-based practice that can effectively neutralize the negative effect of COVID-19 stressors on sleep and work outcomes. The findings of the present study contribute to the employee stress and well-being literature as well as the emerging organizational research on mindfulness.


The linearity of the volume/pressure response during intracranial pressure "reserve" testing.
The intracranial pressure "reserve" test seems to be the most reliable method of determining when the brain's natural mechanisms for pressure compensation for added intracranial volume have been compromised or exhausted. The test employs a timed sequence of intracranial fluid injections, but as a safety precaution injections are discontinued if intracranial pressure remains elevated more than 10 Torr over baseline. In this case, a linear extrapolation is then calculated to determine the elevation which might have been achieved by a full series of injections. However, this linear extrapolation has been criticised on the expectation that an exponential response should be expected. A series of experimental observations in dogs and baboons and a review of clinical records in humans have been made to determine the observed slope of increase following aliquot injection during performance of the intracranial pressure reserve test. In these species the observed response was actually linear in shape rather than exponential. This held true even for different initial baseline values and with different volumes of "lesion" balloon inflations in experimental animals. A theoretic explanation is proposed.


Nurses as boundary-spanners in reducing avoidable hospitalizations among nursing home residents.
An increasing number of nursing home quality improvement efforts are aimed at reducing avoidable hospitalizations of residents. The current study focused on the experiences of nursing home nurses as "boundary-spanners" in the implementation of initiatives aimed at this effort. In-depth, semi-structured interviews were conducted with 76 nursing staff members within 38 nursing homes. Data were analyzed using thematic analysis and an inductive category development approach. Nursing staff described multiple scenarios where they had acted to negotiate the hospitalization decision and described themselves as working both within the nursing home boundary and within the larger system of external stakeholders to avoid a hospital transfer. There is potential for role overload and strain, as nurses are required to provide for complex medical needs within facilities designed to encourage relationship-driven, home-like care. Future efforts to reduce avoidable hospitalizations may benefit by ensuring needed resources are in place to provide clinically complex care and by making efforts to reduce the challenges that emerge when nurses are in the position to span the boundary between the nursing home and outside stakeholders.


A novel small-molecule MRCK inhibitor blocks cancer cell invasion.
The myotonic dystrophy kinase-related CDC42-binding kinases MRCKα and MRCKβ regulate actin-myosin contractility and have been implicated in cancer metastasis. Along with the related ROCK1 and ROCK2 kinases, the MRCK proteins initiate signalling events that lead to contractile force generation which powers cancer cell motility and invasion. A potential strategy for cancer therapy is to reduce metastasis by blocking MRCK activity, either alone or in combination with ROCK inhibition. However, to date no potent small molecule inhibitors have been developed with selectivity towards MRCK. Screening a kinase-focused small molecule chemical library resulted in the identification of compounds with inhibitory activity towards MRCK. Medicinal chemistry combined with in vitro enzyme profiling led to the discovery of 4-chloro-1-(4-piperidyl)-N-[5-(2-pyridyl)-1H-pyrazol-4-yl]pyrazole-3-carboxamide (BDP00005290; abbreviated as BDP5290) as a potent MRCK inhibitor. X-ray crystallography of the MRCKβ kinase domain in complex with BDP5290 revealed how this ligand interacts with the nucleotide binding pocket. BDP5290 demonstrated marked selectivity for MRCKβ over ROCK1 or ROCK2 for inhibition of myosin II light chain (MLC) phosphorylation in cells. While BDP5290 was able to block MLC phosphorylation at both cytoplasmic actin stress fibres and peripheral cortical actin bundles, the ROCK selective inhibitor Y27632 primarily reduced MLC phosphorylation on stress fibres. BDP5290 was also more effective at reducing MDA-MB-231 breast cancer cell invasion through Matrigel than Y27632. Finally, the ability of human SCC12 squamous cell carcinoma cells to invade a three-dimensional collagen matrix was strongly inhibited by 2 μM BDP5290 but not the identical concentration of Y27632, despite equivalent inhibition of MLC phosphorylation. BDP5290 is a potent MRCK inhibitor with activity in cells, resulting in reduced MLC phosphorylation, cell motility and tumour cell invasion. The discovery of this compound will enable further investigations into the biological activities of MRCK proteins and their contributions to cancer progression.


The relationship between facial 3-D morphometry and the perception of attractiveness in children.
The aim of this investigation was to determine whether attractive children differ in their three-dimensional facial characteristics from nonattractive children of the same age, race, and sex. The facial characteristics of 36 boys and 44 girls aged 8 to 9 years were investigated. Frontal and profile photographs were analyzed independently by 21 judges, and, for each view, four groups were obtained: attractive boys, nonattractive boys, attractive girls, and nonattractive girls. For each child, the three-dimensional coordinates of 16 standardized soft tissue facial landmarks were automatically collected using an infrared system and used to calculate several three-dimensional angles, linear distances, and linear distance ratios. Mean values were computed in the eight groups, and attractive and nonattractive children were compared within sex and view. Most children received a different esthetic evaluation in the separate frontal and profile assessments; concordance in both attractive and nonattractive groups was only 50%. Moreover, three-dimensional facial morphometry was not able to separate attractive and nonattractive children.


Diverse effects of interferon alpha on the establishment and reversal of HIV latency.
HIV latency is the major barrier to a cure for people living with HIV (PLWH) on antiretroviral therapy (ART) because the virus persists in long-lived non-proliferating and proliferating latently infected CD4+ T cells. Latently infected CD4+ T cells do not express viral proteins and are therefore not visible to immune mediated clearance. Therefore, identifying interventions that can reverse latency and also enhance immune mediated clearance is of high interest. Interferons (IFNs) have multiple immune enhancing effects and can inhibit HIV replication in activated CD4+ T cells. However, the effects of IFNs on the establishment and reversal of HIV latency is not understood. Using an in vitro model of latency, we demonstrated that plasmacytoid dendritic cells (pDC) inhibit the establishment of HIV latency through secretion of type I IFNα, IFNβ and IFNω but not IFNε or type III IFNλ1 and IFNλ3. However, once latency was established, IFNα but no other IFNs were able to efficiently reverse latency in both an in vitro model of latency and CD4+ T cells collected from PLWH on suppressive ART. Binding of IFNα to its receptor expressed on primary CD4+ T cells did not induce activation of the canonical or non-canonical NFκB pathway but did induce phosphorylation of STAT1, 3 and 5 proteins. STAT5 has been previously demonstrated to bind to the HIV long terminal repeat and activate HIV transcription. We demonstrate diverse effects of interferons on HIV latency with type I IFNα; inhibiting the establishment of latency but also reversing HIV latency once latency is established.


Transporter-mediated absorption is the primary route of entry and is required for passive absorption of intestinal glucose into the blood of conscious dogs.
To determine the contributions of transporter-mediated and passive absorption during an intraduodenal glucose infusion in a large animal model, six mongrel dogs had sampling catheters (portal vein, femoral artery, duodenum), infusion catheters (vena cava, duodenum) and a portal vein flow probe implanted 17 d before an experiment. Protocols consisted of a basal (-30 to 0 min) and an experimental (0-90 min) period. An intraduodenal glucose infusion of 44 micromol/(kg. min) was initiated at t = 0 min. At t = 20 and 80 min, 3-O-[3H]methylglucose and L-[14C]glucose (L-Glc) were injected intraduodenally. Phloridzin, an inhibitor of the Na+/K+ ATP-dependent transporter (SGLT1), was infused from t = 60 to 90 min in the presence of a peripheral isoglycemic clamp. Net gut glucose output was 21.1 +/- 3.0 micromol/(kg. min) from t = 0 to 60 min. Transporter-mediated glucose absorption was calculated using three approaches, which involved either direct measurements or indirect estimates of duodenal glucose analog radioactivities, to account for the assumptions and difficulties inherent to duodenal sampling. Values were essentially the same regardless of calculations used because transporter-mediated absorption was 89 +/- 1%, 90 +/- 2% and 91 +/- 2% of net gut glucose output. Phloridzin-induced inhibition of transporter-mediated absorption completely abolished passive absorption of L-Glc. We conclude that in dogs, transporter-mediated glucose absorption constitutes the vast majority of glucose absorbed from the gut and is required for passive glucose absorption. The method described here is applicable to investigation of the mechanisms of gut glucose absorption under a variety of nutritional, physiologic and pathophysiologic conditions.


Surgical treatment of pigmented villonodular synovitis of the hip.
Pigmented villonodular synovitis of the hip is a rare disease. Synovectomy is generally accepted as the only surgical treatment for the disorder, but there have been few studies with a sufficient sample size and duration of follow-up to allow the evaluation of long-term outcomes. The aim of this study was to determine the long-term outcome of the treatment in sixteen patients. Sixteen patients (nine men and seven women), with a mean age of 35.5 years at the time of surgery, were treated between 1970 and 1996. Complete synovectomy was performed in all patients; in addition, three had a cup arthroplasty, four had a total hip arthroplasty, and one had a monopolar arthroplasty. Clinical and radiographic outcomes were evaluated retrospectively at a mean of 16.7 years postoperatively. Only one patient was followed for less than eight years. Nine patients needed repeat surgery, but only one had recurrent synovitis, as detected with pathological examination fourteen years after treatment with synovectomy and cup arthroplasty. Secondary osteoarthritis developed in all eight patients who had been treated with synovectomy alone, and four of them required a total hip arthroplasty within the follow-up period. These results support earlier data indicating that osteoarthritis consistently develops in patients with pigmented villonodular synovitis of the hip. Complete synovectomy seems to be effective in preventing recurrence of the synovitis, but it does not appear to prevent the development of secondary osteoarthritis.


Lung cancer chemoprevention: a randomized, double-blind trial in Linxian, China.
We examined the effect of supplementation with four different combinations of vitamins and minerals in the prevention of lung cancer mortality among 29,584 healthy adults from Linxian, China. In accord with a partial factorial design, the participants were randomly assigned to take either a vitamin/mineral combination or a placebo for 5.25 years. The combinations tested in this trial were as follows: factor A, retinol and zinc; factor B, riboflavin and niacin; factor C, ascorbic acid and molybdenum; factor D, beta-carotene, alpha-tocopherol, and selenium. Lung cancer deaths (n = 147) identified during the trial period (1986-1991) and 10 years after the trial ended (1991-2001) were the study outcome. No significant differences in lung cancer death rates were found for any of the four combinations of supplements tested in this study, using log-rank tests (all P values are >0.20) or Cox proportional hazards models adjusted for age, sex, commune, and other treatments. No significant interactions were seen for age, sex, or smoking status. Supplementation with combinations of vitamins and minerals at nutrient-repletion levels for 5.25 years did not reduce lung cancer mortality in this nutrient-inadequate population in Linxian, China.


Eosinopenia as Predictor of Poor Outcome in Hospitalized COVID-19 Adult Patients from Waves 1 and 2 of 2020 Pandemic.
During SARS-CoV-2 infection, eosinopenia may reflect a hyperactive immune response. In this study of hospitalized COVID-19 patients, we aimed to better understand the prognostic value of severe eosinopenia (absolute eosinophil count = 0 G/L) and decipher its underlying mechanisms. We retrospectively analyzed the records of COVID-19 patients hospitalized from March to June 2020 in three university hospitals in Marseille, France. We assessed the association between severe eosinopenia and a composite poor outcome in these patients, including the need for oxygen supplementation at >6 L/min, ICU admission, and in-hospital death. Among the 551 COVID-19 patients included in this study, severe eosinopenia was found in 228 (51%) of them on admission to hospital and was associated with a composite poor outcome using multivariate analysis (OR = 2.58; CI95 [1.77−3.75]; p < 0.0001). We found a significant association between the presence of severe eosinopenia on admission and the elevation in C-reactive protein, ferritin, IP-10, and suPAR. The histological findings in a series of 37 autopsies from patients who died from severe COVID-19 and presented with severe eosinopenia showed no pulmonary eosinophil trapping. Severe eosinopenia can be a reliable biomarker associated with a composite poor outcome in hospitalized COVID-19 adult patients. It may reflect the magnitude of immune hyperactivation during severe-to-critical COVID-19.


An unusual presentation of anetoderma: a case report.
Anetoderma is a benign condition with focal loss of dermal elastic tissue resulting in localized areas of flaccid or herniated saclike skin. Currently, anetoderma is classified as either primary (idiopathic), or secondary anetoderma (which is associated with a variety of skin conditions, penicillamine use, or neonatal prematurity). Lesions appear on the upper arms, trunk, and thighs. We report a 14-year-old boy, which was noticed to have had multiple, white, non-pruritic areas on the acral sites of upper and lower extremities for two years. In physical examination, the patient had normal mental development. Skin lesions consisted of scattered, white to skin-colored papules, less than 1 cm in diameter, and with central protrusion, with distribution on dorsal part of the index finger, forearms, distal portion of thighs and calves. Lesions were detected neither on the trunk nor the proximal areas of extremities. There are no sensory changes associated with the lesions. Otherwise, his general health was good. He did not have any medication consumption history. Family history was negative. Laboratory examinations were within normal limits. Skin biopsy from one of his lesions was done, that confirmed the diagnosis of anetoderma. In summary, we report a case of anetoderma on unusual sites of the skin. We could not find similar reports of anetoderma developing on distal extremities without involvement of the upper trunk and proximal arms, in the medical literature.


Two biological rhythms of perception distinguishing between intact and relatively damaged brain function in man.
A simple test of perception, the Critical Flicker Fusion threshold (CFF) was given successively for 20 mins. to 69 healthy subjects aged 7-63 and to 53 comparable neuropsychiatric patients. The latter could be divided into a functionally sick group and a group with brain damage. Auto-correlation analysis revealed significant sine-wave cycles of amplitude and ultradian frequency for the CFF mean scores and the CFF "Scatter* scores. Both cycles of recurrence showed frequencies which distinguished significantly between the total healthy subjects and the patients. Further analysis showed no difference between controls and emotionally sick patients (i.e. those with sociopathy, schizophrenia and manic depressive psychosis) but there was a highly significant difference between these three groups and patients with relatively damaged C.N.S. (i.e. those with mental deficiency, organic brain syndrome and organic dementia). Even among the control group a progressive increase in frequency of these perceptual cycles occurred with advancing age. These CFF results point to the existence of a cycle of perceptual acuity and another of vigilance in the organism. Both appear to relate to the neural integrity of the C.N.S.


The influence of different factors on the oral health status of smoking and nonsmoking adults.
The aim of this study to determine the influence of smoking on self-reported oral health status among university students. Voluntary sample of 669 adults of 18 to 26 years old were invited to participate in the study. They were asked to read a self-designated questionnaire and a covering letter which explained the purpose of the study. The questionnaire addressed self-reported demographics, oral hygiene and smoking habits; knowledge about smoking and its effects on oral health. Data were statistically analyzed using Chi-square test to determine statistically significant differences across the oral health status. The sample included 340 (56.7%) males and 240 (43.3%) females; 56.8% of the subjects were nonsmokers; 43.2% were current smokers, and 17.5% smoke argileh. Almost 24.7% of subjects started smoking because of emotional effects; 66.9% did not smoke because of its harm to health. The percentage of subjects with dental plaque on their teeth was 27.1%, and with calculus was 27.9%, and with stains was 26.9%. About 35.5% of the subjects brushed their teeth once daily. Statistically, significant association was proven between smoking and gender (p < 0.01); and smoking and halitosis (p < 0.01). Smoking is significantly related to esthetics, calculus, tooth stains, halitosis, gingival bleeding, and gender with p < 0.01, p < 0.01, p < 0.01, p < 0.01, p = 0.05, and p < 0.01 respectively.


Exercise therapy and patient education versus intra-articular saline injections in the treatment of knee osteoarthritis: an evidence-based protocol for an open-label randomised controlled trial (the DISCO trial).
Knee osteoarthritis (OA) is a highly prevalent musculoskeletal condition causing pain, physical disability, and reduced quality of life. Exercise and patient education are non-pharmacological interventions for knee OA unanimously recommended as first-line treatments based on extensive research evidence. However, none of the numerous randomised controlled trials of exercise and education for knee OA has used adequate sham/placebo comparison groups because the 'active' ingredients are unknown. Designing and executing an adequate and 'blindable placebo' version of an exercise and education intervention is impossible. Therefore, using an open-label study design, this trial compares the efficacy of a widely used 'state-of-art' exercise and education intervention (Good Life with osteoarthritis in Denmark; GLAD) with presumably inert intra-articular saline injections on improvement in knee pain in patients with knee OA. In this open-label randomised trial, we will include 200 patients with radiographically verified OA of the knee and randomly allocate them to one of two interventions: (i) 8 weeks of exercise and education (GLAD) or (ii) Intra-articular injections of 5 ml isotonic saline every second week for a total of 4 injections. Outcomes are taken at baseline, after 8 weeks of treatment (week 9; primary endpoint) and after an additional 4 weeks of follow-up (week 12). The primary outcome is change from baseline in the Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale score. Secondary outcomes include the Physical function in Activities of Daily Living, Symptoms, and Knee-related Quality of Life subscales of the KOOS, the patients' global assessment of disease impact, physical performance tests, and presence of knee joint swelling. This current trial compares a presumably active treatment (GLAD) with a presumably inert treatment (IA saline injections). Both study interventions have well-established and anticipated similar effects on knee OA symptoms, but the underlying mechanisms are unknown. The interpretation of the results of this trial will likely be difficult and controversial but will contribute to a better understanding of the bias introduced in the effect estimation of classically unblindable exercise and education interventions for knee OA. www.ClinicalTrials.gov NCT03843931 . Prospectively registered on 18 February 2019.


[Visual tests and their score for selection of candidates to higher aviation schools].
In the majority of countries the requirements to refraction and visual acuity into the distance of candidates to aviation schools are extremely high. However, despite rigorous selection the number of students expelled from aviation schools for the reason of myopia remains impressive and even tends to rise. Aside from high incidence of myopia, this is the consequence of considerable visual loading of students and low-informative methods of examination. Simple and easy accommodation tests, the so-called visual loading tests, were applied to 628 candidates to aviation students. Analysis of results showed high informative merits of two procedures, i.e. Evaluation of stability of the visual acuity into the distance (VAD), and Determination of VAD recovery time following preliminary accommodation loading. Subjects with hypermetropia of up to 2.0 dioptres had the best VAD stability. This index was slightly lower in emmetrops; the least VAD stability margin was found in myopathic subjects. After accommodation loading, the VAD recovery time increased by more than 0.75 dioptres in the myopathic subjects and 2.0 dioptres in the hypermetropic subjects. Hence, the visual loading tests show promise as procedures worthy to be included into the program of medical selection of candidates to aviation students.


Adherence to the Mediterranean diet and quality of life in the SUN Project.
Mediterranean diet has been related with reduced morbidity and better well-being. The aim of this study was to assess whether the adherence to the Mediterranean diet were associated with mental and physical health related to quality of life. This analysis included 11 015 participants with 4 years of follow-up in the SUN Project (a multipurpose cohort study based on university graduates from Spain). A validated 136-item food frequency questionnaire was used to assess the adherence to the Mediterranean diet at baseline, according to a nine-point score, presented in four categories (low, low-moderate, moderate-high and high). Health-related quality of life (HRQL) was measured after 4 years of follow-up with the Spanish version of the SF-36 Health Survey. Generalized Linear Models were fitted to assess adjusted mean scores, the regression coefficients (β) and their 95% confidence intervals (95% CIs) for the SF-36 domains according to categories of adherence to Mediterranean diet. Multivariate-adjusted models revealed a significant direct association between adherence to Mediterranean diet and all the physical and most mental health domains (vitality, social functioning and role emotional). Vitality (β=0.50, 95% CI=0.32-0.68) and general health (β=0.45, 95% CI=0.26-0.62) showed the highest coefficients. Mean values for physical functioning, role physical, bodily pain, general health and vitality domains were significantly better with increasing adherence to the Mediterranean diet. Those having improved their initial high diet scores have better scores in physical functioning, general health and vitality. Adherence to the Mediterranean diet seems to be a factor importantly associated with a better HRQL.


Sensitivity of Ca-dependent slow action potentials to methacholine is induced by phosphodiesterase inhibitors in embryonic chick ventricles.
Choline esters fail to depress developed tension or the maximum upstroke velocity (Vmax) of slow action potentials in embryonic chick ventricles, but they inhibit the stimulatory effect of the phosphodiesterase inhibitor methylisobutylxanthine (MIX). The mechanism by which the choline ester methacholine (MCh) counteracts the effects of MIX was examined in ventricular myocardium obtained from 7-day-old embryonic chicks. Four possible hypotheses were 1) that the physiological response to MCh is mediated by cyclic GMP, the production of which is potentiated by MIX; 2) that MCh acts by a mechanism independent of cyclic nucleotides; 3) that the binding of MIX to adenosine receptors induces sensitivity to MCh; or 4) that MCh acts by depressing basal cyclic AMP levels. Interactions between MCh, Angiotensin II and a nonmethylxanthine phosphodiesterase inhibitor (Ro 7-2956) were assessed by measuring tissue levels of cyclic nucleotides and the Vmax of slow action potentials. MCh significantly reduced the basal cyclic AMP level of embryonic chick ventricles, despite having no physiological effect. The results favor the final hypothesis and imply that MCh effects are mediated by inhibition of adenylate cyclase activity. The physiological response of the myocardium to a reduction in basal adenylate cyclase activity appears to be dependent on the initial tissue level of cyclic AMP.


[Suicidality due to inability to pay for care despite home ownership].
A 78-year old-widow lives squalidly in her own apartment. The examination of her cognitive functions reveals a moderate dementia. The needed home care service can not be financed by her small income. By increase of her mortgage a life annuity can be acquired to guaranty regular payment of her interests. This decreases her revenue below the threshold for federal additions to social security rent. This enables to improve the financial health of the demented person and makes regular home care services possible.


Comparative endoscopic evaluation of normal and ulcerated gastric mucosae in Thoroughbred foals.
To contribute to early diagnosis and treatment of gastric ulcer of foals, we examined the gastric mucosa of healthy and affected foals using an endoscope. In healthy foals, the characteristic changes in the development of the squamous mucosa were seen mainly in the squamous mucosa, and maturation of the squamous mucosa in the greater curvature (GC-S) occurred more slowly than that of the squamous mucosa in the lesser curvature (LC-S). Epithelial desquamation in the LC-S and GC-S was observed between 6 and 90 days but was not observed in the LC-S at about 60 days, whereas it was observed in the GC-S until 90 days old. These findings suggest that there is a difference in the development of the gastric mucosa by region and that desquamation continues over a term longer than studies have reported in the past. In the affected foals, the minimum age at which gastric ulcer was observed was 4 days old. Gastric ulcers formed predominantly in the squamous mucosa (LC-S and GC-S) of foals with an immature mucosa before the weaning period, and the peak incidence occurred between 61 and 90 days old. The differences in the ulceration sites were considered to depend on the difference in the development (maturation) stage of the squamous mucosa. The grading score of the gastric ulcer increased with the growth of the affected foals. The gastric ulcer might be enhanced greatly by stress in the weaning period.


Take a second look: it's Kikuchi's disease! A case report and review of literature.
Generalized lymphadenopathy is a common cause of concern for both patients and clinicians. Possible etiologies include infections, malignancies and autoimmune diseases. Kikuchi Fujimoto disease (KFD) is a hyperergic condition that presents with fever, lymphadenopathy and can include systemic involvement, thus being easily mistaken for the above-mentioned entities. We report the case of a previously healthy 18- year old male who presented with a selflimiting generalized lymphadenopathy, high fevers, skin vasculitis and polyserositis. The lymph-node biopsy revealed a histiocytotic necrotizing lymphadenitis, suggestive of Kikuchi's disease. This case emphasizes the importance of KFD in the differential diagnosis of lymphadenopathy, especially in young adults.


Transferable mechanisms of quinolone resistance are more frequent among enterotoxigenic Escherichia coli isolates displaying low-level quinolone resistance.
This study analysed the mechanisms of quinolone resistance among enterotoxigenic Escherichia coli (ETEC) in a periurban area of Lima, Peru. The susceptibility to nalidixic acid and ciprofloxacin, the role of Phe-Arg-b-Naphtylamyde inhibitable-(PAbN) efflux pumps, the presence of mutations in gyrA and parC as well as the presence of aac(6')Ib-cr, qepA, qnrA, qnrB, qnrC, qnrD, qnrVC and oqxAB were determined in 31 ETEC from previous case/control studies of children's diarrhoea. Discordances between disk diffusion, with all isolates showing intermediate or fully resistance to nalidixic acid, and minimal inhibitory concentration (MIC), with 7 isolates being below considered resistance breakpoint, were observed. Twenty-one isolates possessed gyrA mutations (19 S83L, 2 S83A). AAC(6') Ib-cr, QnrS, QnrB and QepA were found in 7, 6, 2 and 1 isolates respectively, with 3 isolates presenting 2 transferable mechanisms of quinolone resistance (TMQR) concomitantly. TMQR were more frequent among isolates with MIC to nalidixic acid ranging from 2 to 16 mg/L (p=0.03), while gyrA mutations were more frequent among isolates with nalidixic acid MIC >= 128 mg/L (p=0.0002). In summary, the mechanisms of quinolone resistance present in ETEC isolates in Peru have been described. Differences in the prevalence of underlying mechanisms associated with final MIC levels were observed. The results suggest two different evolutive strategies to survive in the presence of quinolones related to specific bacterial genetic background.


Excess circulating alternatively activated myeloid (M2) cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis.
Circulating immune cells including autoreactive T cells and monocytes have been documented as key players in maintaining, protecting and repairing the central nervous system (CNS) in health and disease. Here, we hypothesized that neurodegenerative diseases might be associated, similarly to tumors, with increased levels of circulating peripheral myeloid derived suppressor cells (MDSCs), representing a subset of suppressor cells that often expand under pathological conditions and inhibit possible recruitment of helper T cells needed for fighting off the disease. We tested this working hypothesis in amyotrophic lateral sclerosis (ALS) and its mouse model, which are characterized by a rapid progression once clinical symptoms are evident. Adaptive transfer of alternatively activated myeloid (M2) cells, which homed to the spleen and exhibited immune suppressive activity in G93A mutant superoxide dismutase-1 (mSOD1) mice at a stage before emergence of disease symptoms, resulted in earlier appearance of disease symptoms and shorter life expectancy. The same protocol mitigated the inflammation-induced disease model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), which requires circulating T cells for disease induction. Analysis of whole peripheral blood samples obtained from 28 patients suffering from sporadic ALS (sALS), revealed a two-fold increase in the percentage of circulating MDSCs (LIN(-/Low)HLA-DR(-)CD33(+)) compared to controls. Taken together, these results emphasize the distinct requirements for fighting the inflammatory neurodegenerative disease, multiple sclerosis, and the neurodegenerative disease, ALS, though both share a local inflammatory component. Moreover, the increased levels of circulating MDSCs in ALS patients indicates the operation of systemic mechanisms that might lead to an impairment of T cell reactivity needed to overcome the disease conditions within the CNS. This high level of suppressive immune cells might represent a risk factor and a novel target for therapeutic intervention in ALS at least at the early stage.


Structural elucidation of N-oxidized clemastine metabolites by liquid chromatography/tandem mass spectrometry and the use of Cunninghamella elegans to facilitate drug metabolite identification.
Cunninghamella elegans is a filamentous fungus that has been shown to biotransform drugs into the same metabolites as mammals. In this paper we describe the use of C. elegans to aid the identification of clemastine metabolites since high concentrations of the metabolites were produced and MS(n) experiments were facilitated. The combination of liquid chromatography and tandem mass spectrometry with two different ionization techniques and hydrogen/deuterium exchange were used for structural elucidation of the clemastine metabolites. Norclemastine, four isomers of hydroxylated clemastine, and two N-oxide metabolites were described for the first time in C. elegans incubations. The N-oxidations were confirmed by hydrogen/deuterium exchange and deoxygenation (-16 Da) upon atmospheric pressure chemical ionization mass spectrometry. By MS(n) fragmentation it was concluded that two of the hydroxylated metabolites were oxidized on the methylpyrridyl moiety, one on the aromatic ring with the chloro substituent, and one on the aromatic ring without the chlorine.


The influence of natural photoperiod on seasonal torpor expression of two opportunistic marsupial hibernators.
Many mammals use torpor throughout the year but the individual contributions of environmental variables to seasonal changes in torpor expression are often difficult to tease apart. In many mammals, torpor is most often used opportunistically in response to decreased ambient temperature (T a ) and food availability, but information on how seasonally changing photoperiod per se influences torpor patterns is scant. Therefore, we quantified patterns of torpor use in response to natural photoperiod in captive marsupial pygmy-possums held at near-constant T a with a stable food supply over a period of 19 months. Western pygmy-possums (Cercartetus concinnus) and eastern pygmy-possums (C. nanus) used spontaneous torpor in every month of the year; in total we measured >1100 individual torpor bouts. Torpor bout duration was >60 % longer in winter than in summer and increased with decreasing day length for both species. Interestingly, the duration of torpor appeared to be adjusted at both the beginning and end of bouts because the time of entry into and rewarming from torpor relative to sunrise and sunset, respectively, changed with season. We propose that this reflects a synchronisation of torpor timing with foraging periods in the wild, which would enable animals to maintain a high body mass year-round by maximising both energy savings via torpor and energy input via food consumption. Our study suggests that photoperiod makes a significant contribution to the seasonal change in torpor bout duration of small hibernating mammals that use torpor throughout the year.


FOXL1, a novel candidate tumor suppressor, inhibits tumor aggressiveness and predicts outcome in human pancreatic cancer.
The forkhead box L1 (FOXL1) transcription factor regulates epithelial proliferation and development of gastrointestinal tract and has been implicated in gastrointestinal tumorigenesis in mouse models. However, the role of FOXL1 in pancreatic cancer development and progression remains to be elucidated. Here, we report that higher expression of FOXL1 is significantly associated with better clinical outcome in human pancreatic ductal adenocarcinoma (PDAC). A lower FOXL1 expression is correlated with metastasis and advanced pathologic stage of pancreatic cancer. Mechanistic analyses showed that overexpression of FOXL1 induces apoptosis and inhibits proliferation and invasion in pancreatic cancer cells, whereas silencing of FOXL1 by siRNA inhibits apoptosis and enhances tumor cell growth and invasion. Furthermore, FOXL1 overexpression significantly suppressed the growth of tumor xenografts in nude mice. FOXL1 promoted apoptosis partly through the induction of TNF-related apoptosis-inducing ligand (TRAIL) in pancreatic cancer cells. In addition, FOXL1 suppressed the transcription of zinc finger E-box-binding homeobox 1 (ZEB1), an activator of epithelial-mesenchymal transition, and the negative regulation of ZEB1 contributed to the inhibitory effect of FOXL1 on tumor cell invasion. Taken together, our findings suggest that FOXL1 expression is a candidate predictor of clinical outcome in patients with resected PDAC and it plays an inhibitory role in pancreatic tumor progression.


Computational estimation of potential inhibitors from known drugs against the main protease of SARS-CoV-2.
The coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide recently, leading to global social and economic disruption. Although the emergently approved vaccine programs against SARS-CoV-2 have been rolled out globally, the number of COVID-19 daily cases and deaths has remained significantly high. Here, we attempt to computationally screen for possible medications for COVID-19 via rapidly estimating the highly potential inhibitors from an FDA-approved drug database against the main protease (Mpro) of SARS-CoV-2. The approach combined molecular docking and fast pulling of ligand (FPL) simulations that were demonstrated to be accurate and suitable for quick prediction of SARS-CoV-2 Mpro inhibitors. The results suggested that twenty-seven compounds were capable of strongly associating with SARS-CoV-2 Mpro. Among them, the seven top leads are daclatasvir, teniposide, etoposide, levoleucovorin, naldemedine, cabozantinib, and irinotecan. The potential application of these drugs in COVID-19 therapy has thus been discussed.


SUMO-specific protease 1 is essential for stabilization of HIF1alpha during hypoxia.
SUMOylation is a dynamic process, catalyzed by SUMO-specific ligases and reversed by Sentrin/SUMO-specific proteases (SENPs). The physiologic consequences of SUMOylation and deSUMOylation are not fully understood. Here we investigate the phenotypes of mice lacking SENP1 and find that SENP1(-/-) embryos show severe fetal anemia stemming from deficient erythropoietin (Epo) production and die midgestation. We determine that SENP1 controls Epo production by regulating the stability of hypoxia-inducible factor 1alpha (HIF1alpha) during hypoxia. Hypoxia induces SUMOylation of HIF1alpha, which promotes its binding to a ubiquitin ligase, von Hippel-Lindau (VHL) protein, through a proline hydroxylation-independent mechanism, leading to its ubiquitination and degradation. In SENP1(-/-) MEFs, hypoxia-induced transcription of HIF1alpha-dependent genes such as vascular endothelial growth factor (VEGF) and glucose transporter 1 (Glut-1) is markedly reduced. These results show that SENP1 plays a key role in the regulation of the hypoxic response through regulation of HIF1alpha stability and that SUMOylation can serve as a direct signal for ubiquitin-dependent degradation.


The Compromising Interpretive Model as a Harm Reduction Strategy for Families that Have Chosen High School Football.
In a reply to Ross, I argue that, as head injuries often lack external indicators, it is imperative that youth-patient-athletes themselves be convinced to report these injuries. Parents, although part of the pediatric triad, will be no help if the adolescent chooses to conceal the information from them as well. Further, I explain why a more deliberate focus on the role of parents in this relationship does not alter my support of the compromising interpretive model as a harm reduction strategy.


Involvement of gap junctions in the manifestation and control of the duration of seizures in rats in vivo.
The possible role of gap junctions in the manifestation and control of the duration of seizures was tested on the 4-aminopyridine-induced epilepsy model in rats in vivo, by using electrophysiologic, pharmacologic, and molecular biologic techniques. METHODS; In electrophysiologic experiments, the functional states of the gap junctions were manipulated with a specific blocker (carbenoxolone) or opener (trimethylamine) at the already active focus of adult, anesthetized rats, 60 min after the induction of the first seizure, which was repeated spontaneously thereafter. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) amplification was used to measure the levels of connexin (Cx) 32, 43, and 36 messenger RNAs (mRNAs) prepared from the areas of the already active primary and mirror foci. After repeated seizures, the expression levels of Cx32, Cx43, and Cx36 mRNAs at the epileptic foci were increased significantly. Blockade of the gap junctions with carbenoxolone shortened the duration of seizures and decreased the amplitude of the seizure discharges, whereas their opening with trimethylamine lengthened the duration and increased the amplitude. Secondary epileptogenesis was facilitated when the gap junctions were opened. CONCLUSIONS; Our findings support the idea that, in epileptic foci, the gap junctions are involved in the expression of rhythmic ictal discharges and in the control of the duration and propagation of the individual seizures in vivo.


The deletion in both common types of hereditary persistence of fetal hemoglobin is approximately 105 kilobases.
The most common forms of hereditary persistence of fetal hemoglobin (HPFH) involve large deletions that remove the adult delta and beta genes but leave the paired fetal genes (G gamma and A gamma) intact. The size of these deletions has previously eluded exact definition. Using pulsed-field gel electrophoresis and the enzyme SfiI, which cuts only rarely in genomic DNA, we have constructed a large-scale restriction map of the beta-globin cluster in normal and HPFH DNA. The deletions in HPFH-1, which occurs in American blacks, and in HPFH-2, which occurs in Ghanaian blacks, are found to be approximately 105 kilobases (kb) in length, though the endpoints are staggered by approximately 5 kb. The fact that two previously reported gamma delta beta-thalassemia deletions to the 5' side of the beta-globin cluster are also about 100 kb suggests a common mechanism, possibly involving the loss of a complete chromatin loop.


'Overjoyed that I can go outside': Using walking interviews to learn about the lived experience and meaning of neighbourhood for people living with dementia.
This study explores the relationships between people living with dementia and their neighbourhood as they venture out from home on a regular and often routine basis. Here, we report findings from the Swedish field site of an international 5-year project: Neighbourhoods: our people, our places. The aims of this study were to investigate the lived experience of the neighbourhood for people with dementia and through this to better understand the meaning that neighbourhood held for the participants. In this study, we focus on the walking interviews which were conducted with 14 community-dwelling people with dementia (11 men and 3 women) and were analysed using an interpretative phenomenological method. Four themes were revealed from these interviews: life narratives embedded within neighbourhood; the support of selfhood and wellbeing through movement; the neighbourhood as an immediate social context; and restorative connections to nature. These themes were distilled into the 'essence' of what neighbourhood meant for the people we interviewed: A walkable area of subjective significance and social opportunity in which to move freely and feel rejuvenated. We have found that the neighbourhood for community-dwelling people with dementia holds a sense of attachment and offers the potential for freedom of movement. Our research indicates that a dementia diagnosis doesn't necessarily reduce this freedom of movement. The implications for practice and policy are considered: future research should explore and pay closer attention to the diverse living conditions of people living with dementia, and not least the particular challenges faced by people living alone with dementia.


[Oxidase activity of ceruloplasmin and the state of hemocoagulation in patients with chronic pancreatitis].
We examined oxidase activity of ceruloplasmin, fibrinogen content in the blood serum and the state of hemocoagulation in 80 patients with chronic pancreatitis of different etiology. The presence of ceruloplasmin was considered to be paraphenylenediamine oxidase. It was shown that at the acute stage of the disease oxidase activity of ceruloplasmin is increased and depends on the severity, duration and presence of complications. An increase of the anti-oxidant action protein content is accompanied by hypercoagulation and an increase of the fibrinogen content. Data are given on the availability of correlation relationship between the fibrinogen content and general blood coagulation constant.


Clinical characteristics and treatment outcomes of vancomycin-resistant Enterococcus faecium bacteremia.
Vancomycin-resistant Enterococcus faecium (VRE-fm) bacteremia causes significant mortality in hospitalized patients. We sought to investigate clinical characteristics, treatment outcomes, and microbiological eradication associated with VRE-fm bacteremia. A retrospective cohort study was conducted and included 210 adult patients admitted between January 1, 2011 and December 31, 2015. The mean Pitt bacteremia score was 4.7. ICU stay (48.6%) and mechanical ventilation (46.2%) were common. Diabetes mellitus was the most common concomitant disease (43.3%), followed by malignancies, including hematologic malignancies (14.3%) and solid cancers (28.1%). The 14-day and 28-day mortality rates were 37.1% and 50.5%, respectively. Linezolid or daptomycin treatment for at least 10 days and higher Pitt bacteremia scores were independently associated with 14-day and 28-day mortality. Longer treatment duration of linezolid or daptomycin predicted microbiological eradication independently. Daptomycin-treated patients tended to have higher 14-day and 28-day mortality, and lower microbial eradication rates (20.8% versus 8.7%; 40.6% versus 26.1%; 14.1% versus 26.1%; respectively) than linezolid-treated patients, and cumulative survival rates at 14 and 28 days tended to be lower in patients who received low-dose daptomycin (<10 mg/kg/day) than that in those who received linezolid and high-dose daptomycin (≥10 mg/kg/day); however, the differences were not statistically significant. Higher disease severity and inappropriate treatment were associated with increased mortality and longer treatment duration of linezolid or daptomycin was associated with microbial eradication for the patient with VRE-fm bacteremia.


Characterization and genetic analysis of a light- and temperature-sensitive spotted-leaf mutant in rice.
A rice spotted-leaf mutant was isolated from an ethane methyl sulfonate (EMS) -induced IR64 mutant bank. The mutant, designated as spl30 (spotted-leaf30), displayed normal green leaf color under shade but exhibited red-brown lesions under natural summer field conditions. Initiation of the lesions was induced by light and the symptom was enhanced at 33 (°) C relative to 26 (°) C. Histochemical staining did not show cell death around the red-brown lesions. Chlorophyll contents in the mutant were significantly lower than those of the wild type while the ratio of chlorophyll a/b remained the same, indicating that spl30 was impaired in biosynthesis or degradation of chlorophyll. Disease reaction patterns of the mutant to Xanthomonas oryzae pv. oryzae were largely unchanged to most races tested except for a few strains. Genetic analysis showed that the mutation was controlled by a single recessive gene, tentatively named spl30(t), which co-segregated with RM15380 on chromosome 3, and was delimited to a 94 kb region between RM15380 and RM15383. Spl30(t) is likely a novel rice spotted-leaf gene since no other similar genes have been identified near the chromosomal region. The genetic data and recombination populations provided in this study will enable further fine-mapping and cloning of the gene.


Polarization management based on dipolar interferences and lattice couplings.
We have achieved efficient polarization manipulations based on dipolar interferences and lattice couplings in one-dimensional cylindrical metalattices. First, we employ the scattering asymmetry factor g to quantify the directional scattering ability and find the maximum |g|max=1/2 for a cylinder with effective excitations of electric and magnetic dipoles simultaneously. Further, the strong negative-g (gp = -0.38) for p-polarization and positive-g (gs = 0.68) for s-polarization are obtained within a narrow visible band using c-Si with experimental data. Inspired by the polarization-dependent phenomena, we design a metalattice-based linear polarizer considering lattice effects with an optimal particle arrangement. The metalattice performs near-perfect reflection for p-polarized waves but with zero reflection for s-polarized waves with large extinction ratios for transmission (17 dB) and reflection (24 dB). The perfect functionalities can be attributed to the near-field lattice couplings with dipolar interferences. And, we reveal that the polarization-dependent scattering coefficients, which are sensitive to the lattice period, can be largely tuned owing to lattice effects, therefore contributing to modifying far-field scattering patterns. More specifically, the proposed linear polarizers also show robust and reliable functionalities when considering lattice imperfections, the effects of system sizes, oblique incident angles, and the tunbility for different working wavelengths. The present study paves a way to stimulate many advanced practical implements based on multipolar interferences and lattice couplings.


Determining functional activity profiles in patients with upper extremity disorders: is there effect modification by hand-grip strength?
The purposes of this study were to investigate the effect of hand-grip strength (HGS) on the Disabilities of the Arm, Shoulder, and Hand (DASH) score in women with upper extremity musculoskeletal disorders (UEMDs) living in rural communities and examine whether upper extremity diseases affected upper extremity functional activity in each group (normal/low HGS) and whether grip strength (GS) was an effect modifier in upper extremity functional activity. A total of 239 women older than 60 years who had completed a medical workup for epicondylitis, rotator cuff tears, and/or hand osteoarthritis were included in the final study. Functional activity was assessed by DASH, and muscle strength was measured by GS. Low HGS was defined according to the Asian Working Group for Sarcopenia (HGS <18 kg in women). Pearson correlation analysis was performed to evaluate the relationship between HGS and the DASH score. A multiple regression analysis was performed after defining DASH as a dependent variable and dividing subjects into two groups (low HGS and normal HGS). Statistical analyses were performed using SPSS Statistics V.24. HGS in the participants correlated with the DASH score (r=-0.320, P<0.001). In the low HGS group, waist circumference (B=-0.526, P=0.010) and the DASH score were significantly correlated. In addition, DASH scores were statistically significantly increased as the number of upper extremity diseases increased to 2 (B=11.592, P=0.016) and 3 (B=15.716, P=0.001). The DASH score in the normal HGS group was correlated with the Patient Health Questionnaire-2 score (β=2.680, P<0.001) after adjusting covariates. We found that HGS in UEMD patients affected health-related quality of life as measured by the DASH. Maintaining hand muscle strength may improve patient functional activity in age-related UEMDs.


Structure-From-Motion in Spherical Video Using the von Mises-Fisher Distribution.
In this paper, we present a complete pipeline for computing structure-from-motion from the sequences of spherical images. We revisit problems from multiview geometry in the context of spherical images. In particular, we propose methods suited to spherical camera geometry for the spherical-n-point problem (estimating camera pose for a spherical image) and calibrated spherical reconstruction (estimating the position of a 3-D point from multiple spherical images). We introduce a new probabilistic interpretation of spherical structure-from-motion which uses the von Mises-Fisher distribution to model noise in spherical feature point positions. This model provides an alternate objective function that we use in bundle adjustment. We evaluate our methods quantitatively and qualitatively on both synthetic and real world data and show that our methods developed for spherical images outperform straightforward adaptations of methods developed for perspective images. As an application of our method, we use the structure-from-motion output to stabilise the viewing direction in fully spherical video.


Idiopathic giant-cell myocarditis--natural history and treatment. Multicenter Giant Cell Myocarditis Study Group Investigators.
Idiopathic giant-cell myocarditis is a rare and frequently fatal disorder. We used a multicenter data base to define the natural history of giant-cell myocarditis and the effect of treatment. We identified 63 patients with idiopathic giant-cell myocarditis through journal announcements and direct mailings to cardiovascular centers worldwide. The patients consisted of 33 men and 30 women with an average age of 42.6 years; 88 percent were white, 5 percent were black, 5 percent were Southeast Asian or Indian, and 2 percent were Middle Eastern. Most presented with congestive heart failure (47 patients, or 75 percent), ventricular arrhythmia (9 patients, or 14 percent), or heart block (3 patients, or 5 percent), although in some cases the initial symptoms resembled those of acute myocardial infarction (4 patients). Nineteen percent had associated autoimmune disorders. The rate of survival was worse than among 111 patients with lymphocytic myocarditis in the Myocarditis Treatment Trial (P<0.001); among our patients, the rate of death or cardiac transplantation was 89 percent, and median survival was only 5.5 months from the onset of symptoms. The 22 patients treated with corticosteroids and cyclosporine, azathioprine, or both therapies survived for an average of 12.3 months, as compared with an average of 3.0 months for the 30 patients who received no immunosuppressive therapy (P=0.001). Of the 34 patients who underwent heart transplantation, 9 (26 percent) had a giant-cell infiltrate in the transplanted heart and 1 died of recurrent giant-cell myocarditis. Giant-cell myocarditis is a disease of relatively young, predominantly healthy adults. Patients usually die of heart failure and ventricular arrhythmia unless cardiac transplantation is performed. Despite the possibility of fatal disease recurrence, transplantation is the treatment of choice for most patients.


Identifying cumulative trauma disorders of the upper extremity in workers' compensation databases.
Impeding the use of workers' compensation databases for surveillance of cumulative trauma disorder of the upper extremity (CTDUE) is the lack of valid and reliable extraction strategies. Using the Z795-96 Coding of Work Injury or Disease Information standard, an algorithm was developed to classify claims as definite, possible, or non-CTDUE. Reliability was assessed with standardized claim reviews. Moderate to substantial agreement (Kappa = 0.48, 95% CI 0.42-0.54, n = 328; weighted Kappa = 0.75, 95% CI 0.70-0.80, n = 328) was demonstrated. The algorithm produced relatively homogeneous groups of definite and non-CTDUE claims but 29.1% of the possible CTDUE claims were categorized as definite CTDUE by claim review. Part of body agreement was almost perfect (Kappa = 0.81-1.00) when determining whether the upper extremity or specific parts of the upper extremity were involved. The algorithm can be used to estimate the number of CTDUE and extract homogeneous groups of definite and non-CTDUE claims. Furthermore, certain upper extremity part of body codes can be used to target anatomically defined claims.


Multitrophic interactions involving genetically modified potatoes, nontarget aphids, natural enemies and hyperparasitoids.
Genetically modified (GM) potatoes expressing a cysteine proteinase inhibitor (cystatin) have been developed as an option for the management of plant parasitic nematodes. The relative impact of such plants on predators and parasitoids (natural enemies) of nontarget insects was determined in a field trial. The trial consisted of GM plants, control plants grown in soil treated with a nematicide and untreated control plants. The quantity of nontarget aphids and their quality as hosts for natural enemies were studied. Aphid density was significantly reduced by nematicide treatment and few natural enemies were recorded from treated potatoes during the study. In contrast, similar numbers of aphids and their more abundant predators were recorded from the untreated control and the GM potatoes. The size of aphids on GM and control plants was recorded twice during the study. During the first sampling period (2-9 July) aphids clip-caged on GM plants were smaller than those on control plants. During the second sampling period (23-30 July) there was no difference in aphid size between those from the GM and control plants. Host size is an important component of host quality. It can affect the size and fecundity of parasitoid females and the sex ratio of their offspring. However, neither the fitness of females of Aphidius ervi, the most prevalent primary parasitoid, nor the sex ratio of their progeny, were affected when the parasitoids developed on aphids feeding on GM plants. Two guilds of secondary parasitoid were also recorded during the study. The fitness of the most abundant species, Aspahes vulgaris, was not affected when it developed on hosts from GM plants. The transgene product, OC I Delta D86, was not detected in aphids that had fed on GM plants in the field, suggesting that there is minimal secondary exposure of natural enemies to the inhibitor. The results indicate that transgenic nematode resistance is potentially more compatible with aphid biological control than is current nematicide use.


Allograft-induced proliferation of vascular smooth muscle cells: potential targets for treating transplant vasculopathy.
Despite advances in immunosuppressive drugs, coronary artery transplant vasculopathy (CATV) is the major cause of graft failure that limits long-term survival of cardiac transplantation. The pathogenesis of CATV involves a chronic immune response of the recipient to the donor vasculature in which activated recipient immune cells damage the endothelium and produce cytokines, resulting in vascular smooth muscle cell (VSMC) activation. Activated VSMC migrate from the media into the lumen, proliferate, and elaborate cytokines and matrix proteins, resulting in loss of lumen diameter and vascular contractility. Because of its extensive nature, interventions which are successful in patients with conventional coronary artery disease are often not applicable to the majority of patients with CATV. Although intended for immune suppression, many immunosuppressive agents owe at least part of their efficacy to their anti proliferative effects on VSMC, including rapamycin, mycophenolic acid, cyclosporin, calcium channel blockers, and HMG CoA reductase inhibitors. Because activation of VSMC is responsible for most of the obliterative arterial intimal thickening present in solid organ allografts, the induction of expression of a selected set of genes may reflect the status of acceptance of the vasculature by the recipient, and the activation, migration, and proliferation of VSMC represent potential points for therapeutic intervention. The risk of infection and malignancy associated with immunosuppressive therapy further promote the need to identify a molecular target which directly modulates the VSMC response to injury. This review will summarize the anti proliferative effects that immunosuppressive drugs have on VSMC proliferation. We will also describe efforts to define the genes which regulate the vascular response to allograft injury, and describe how some of these proteins may represent targets to reduce VSMC proliferation and attenuate CATV.


Purified hepatitis B virus induces human mesangial cell proliferation and extracellular matrix expression in vitro.
Hepatitis B virus (HBV) induces proliferation of human mesangial cells (HMCs), and extracellular matrix expression through the deposition of immune complexes in renal tissue. However, it is unclear whether HBV can directly affect HMCs. In this study, the effects of purified HBV on HMC proliferation and extracellular matrix expression in vitro was determined. HBV was purified using sucrose density gradient centrifugation. HMCs were co-cultured with purified HBV (104-106 copies/ml) for 48 h, and cell proliferation determined using 5-ethynyl-2'-deoxyuridine immunofluorescence assays. After HMCs were co-cultured with 106 copies/ml purified HBV for 0, 12, 24, 36 and 48 h, expression of type IV collagen and fibronectin was measured using enzyme-linked immunosorbent assays. Three titers of purified HBV (10(4), 10(5), and 10(6) copies/ml) induced HMC proliferation, with the proportion of increases in cell numbers at 24.7 ± 4.3, 31.2 ± 9.4, and 36.8 ± 7.5%, respectively. All these increases were significantly higher than those for the control group (13.6 ± 4.2%) (All p < 0.05). Purified HBV (10(6) copies/ml) significantly increased the levels of type IV collagen and fibronectin in supernatants compared with the control group at 12 and 48 h (All p < 0.05). Purified HBV can directly promote HMC proliferation and expression of type IV collagen and fibronectin, and could be involved in the pathogenesis of HBV-associated glomerulonephritis.


A cross-cultural comparison of autistic traits in the UK, India and Malaysia.
The disorder of autism is widely recognised throughout the world. However, the diagnostic criteria and theories of autism are based on research predominantly conducted in Western cultures. Here we compare the expression of autistic traits in a sample of neurotypical individuals from one Western culture (UK) and two Eastern cultures (India and Malaysia), using the Autism-spectrum Quotient (AQ) in order to identify possible cultural differences in the expression of autistic traits. Behaviours associated with autistic traits were reported to a greater extent in the Eastern cultures than the Western culture. Males scored higher than females and science students scored higher than non-science students in each culture. Indian students scored higher than both other groups on the Imagination sub-scale, Malaysian students scored higher than both other groups on the Attention Switching sub-scale. The underlying factor structures of the AQ for each population were derived and discussed.


Preparation of occupational therapists to work in early intervention programs.
This paper presents the results of a survey of 43 occupational therapy academic programs regarding their preparation of students to work with young children with special needs. The number of instructional hours devoted to topics related to services for infants or toddlers and their families varied greatly. Some programs plan an increase in hours but are limited by the total hours available within the curriculum. This paper also shares the recommendations of a panel of occupational therapists with expertise in early intervention and entry-level education. The panel was concerned with the quality of preparation of therapists entering early intervention programs and encouraged the profession to review the amount of course work within each curriculum that introduces students to basic knowledge and skills related to early intervention. Some knowledge, such as the consultant's role and working with families of persons who are physically or mentally challenged, are common to other practice areas. The panel stressed that students be taught strategies for obtaining the training necessary for postgraduate entry into a specialty area such as early intervention.


Proteasome alpha-type subunit C9 is a primary target of autoantibodies in sera of patients with myositis and systemic lupus erythematosus.
Autoantibodies occur in low frequencies among patients with myositis characterizing only distinct subsets of this disease. Most of these known antibodies are directed to enzymatically active complexes. The 20S proteasome represents an essential cytoplasmatic protein complex for intracellular nonlysosomal protein degradation, and is involved in major histocompatibility complex class I restricted antigen processing. In this study we investigated whether the 20S proteasome complex is an antibody target in myositis and in other autoimmune diseases. 34 sera of poly/dermatomyositis patients were assayed for antiproteasomal antibodies using enzyme-linked immunosorbent assay, immunoblot, and two-dimensional non-equilibrium pH gradient electrophoresis (NEPHGE). Sera was from patients with systemic lupus erythematosus (SLE), mixed connective tissue disease, and rheumatoid arthritis; healthy volunteers served as controls. In 62% (21/34) of the cases sera from patients with myositis and in 58% (30/52) of the cases sera from patients with SLE reacted with the 20S proteasome. These frequencies exceeded those of sera from patients with mixed connective tissue disease, rheumatoid arthritis, and healthy controls. The alpha-type subunit C9 of the 20S proteasome was determined to be the predominant target of the autoimmune sera in myositis and SLE. Lacking other frequent autoantibodies in myositis, the antiproteasome antibodies are the most common humoral immune response so far detected in this disease entity.


Bayesian phylogeographic inferences reveal contrasting colonization dynamics among European groundwater isopods.
The potentially important role of northern microrefugia during postglacial dispersal is challenging the view of southern Europe as a refuge and source area of European biota. In groundwaters, large geographic ranges of presumably good dispersers are increasingly suspected to consist of assemblages of cryptic species with narrow ranges. Moreover, a large species range, even when confirmed by molecular evidence, tells us little about the spatiotemporal dynamics of dispersal. Here, we used phylogenetic inferences, species delineation methods and Bayesian phylogeographic diffusion models to test for the likelihood of postglacial colonization from distant refugia among five morphospecies of Proasellus (Isopoda, Asellidae). All morphospecies except one were monophyletic, but they comprised a total of 15-17 cryptic species. Three cryptic species retained ranges that spanned a distance >650 km, similar to that of the nominal morphospecies. Bayesian diffusion models based on mitochondrial markers revealed considerable spatiotemporal heterogeneity in dispersal rates, suggesting that short-time dispersal windows were instrumental in shaping species ranges. Only one species was found to experience a recent, presumably postglacial, range expansion. The Jura and Alpine foothills probably played a major role in maintaining diversity within Proasellus in northern regions by acting both as diversification hotspots and Pleistocene refugia. Gaining insight into the spatiotemporal heterogeneity of dispersal rates revealed contrasting colonization dynamics among species that were not consistent with a global postglacial colonization of Europe from distant refugia.


Remote triggered release of doxorubicin in tumors by synergistic application of thermosensitive liposomes and gold nanorods.
Delivery of chemotherapeutic agents after encapsulation in nanocarriers such as liposomes diminishes side-effects, as PEGylated nanocarrier pharmacokinetics decrease dosing to healthy tissues and accumulate in tumors due to the enhanced permeability and retention effect. Once in the tumor, however, dosing of the chemotherapeutic to tumor cells is limited potentially by the rate of release from the carriers and the size-constrained, poor diffusivity of nanocarriers in tumor interstitium. Here, we report the design and fabrication of a thermosensitive liposomal nanocarrier that maintains its encapsulation stability with a high concentration of doxorubicin payload, thereby minimizing "leak" and attendant toxicity. When used synergistically with PEGylated gold nanorods and near-infrared stimulation, remote triggered release of doxorubicin from thermosensitive liposomes was achieved in a mouse tumor model of human glioblastoma (U87), resulting in a significant increase in efficacy when compared to nontriggered or nonthermosensitive PEGylated liposomes. This enhancement in efficacy is attributed to increase in tumor-site apoptosis, as was evident from noninvasive apoptosis imaging using Annexin-Vivo 750 probe. This strategy affords remotely triggered control of tumor dosing of nanocarrier-encapsulated doxorubicin without sacrificing the ability to differentially dose drugs to tumors via the enhanced permeation and retention effect.


Quantitation of serum monoclonal proteins: relationship between agarose gel electrophoresis and immunonephelometry.
Previous comparisons of monoclonal protein quantification identified a bias between serum protein electrophoresis (SPEP) and immunonephelometry (NEPH). We reviewed data from 2845 patients in whom a single sample provided a gamma fraction M-spike by SPEP, a heavy chain isotype by immunofixation electrophoresis (IFE), and an Ig quantification by NEPH. We examined the relationship between SPEP and NEPH. Selected sera with high monoclonal protein concentrations were diluted and reassessed. For all isotypes, the relationship between SPEP and NEPH was best fitted with cubic curves. We determined the concentrations of each isotype that fitted a linear relationship. IgA had the best correspondence (slope 0.92, 95% CI 0.87-1.02), whereas IgM demonstrated a systematic bias of higher values by NEPH (slope 1.80, 95% CI 1.68-1.92). IgG demonstrated a nonlinear relationship between SPEP and NEPH, with a linear region <19.2 g/L having a slope of 0.83 (95% CI 0.79-0.89) and a second linear region having a slope of 1.47 (95% CI 1.39-1.53) at higher concentrations. Dilutions of high-concentration IgG monoclonal proteins were linear by NEPH and nonlinear by SPEP. There are systematic differences in the quantification of monoclonal IgM and IgG by SPEP and NEPH. The bias in IgM is from NEPH overestimation. The nonlinearity of SPEP at high monoclonal IgG concentrations may obscure changes in plasma cell populations. Clinicians should be made aware of the biases and nonlinearity in these tests to make proper conclusions regarding treatment response.


[The role of oxidative stress in normal and pathological adaptive reactions].
After a brief presentation of the data concerning the mechanism of production of oxidative stress as an expression of cellular and molecular stressing aggression, the main actions and functional implications of the excess of free radicals at the level of the main tissues and organs are presented. Emphasis is made on the nuclear, cytosolic and membrane alterations produced by the lipid peroxidation phenomena and the cell protein degradation induced by the oxidative stress. Special attention is given to the beneficial and harmful properties of the free radical species of oxygen and nitrogen, beginning with their involvement in the production of the normal adaptive reactions and ending with their involvement in the pathogenesis of various pathological states. In the group of beneficial effects are included along with the antibacterial and antiviral properties of the free radicals and their participation in the autoregulation of the local arteriolar-capillary circulation network. As harmful properties are mentioned the cellular destructive phenomena produced by the free radicals, which are considered as the generators of a true radicals pathology (senescence, atherogenesis, cancerogenesis, neurodegenerative diseases, etc).


Isotopic niche reflects stress-induced variability in physiological status.
The isotopic niche has become an established concept in trophic ecology. However, the assumptions behind this approach have rarely been evaluated. Evidence is accumulating that physiological stress can affect both magnitude and inter-individual variability of the isotopic signature in consumers via alterations in metabolic pathways. We hypothesized that stress factors (inadequate nutrition, parasite infestations, and exposure to toxic substances or varying oxygen conditions) might lead to suboptimal physiological performance and altered stable isotope signatures. The latter can be misinterpreted as alterations in isotopic niche. This hypothesis was tested by inducing physiological stress in the deposit-feeding amphipod Monoporeia affinis exposed to either different feeding regimes or contaminated sediments. In the amphipods, we measured body condition indices or reproductive output to assess growth status and δ13C and δ15N values to derive isotope niche metrics. As hypothesized, greater isotopic niche estimates were derived for the stressed animals compared to the control groups. Moreover, the δ15N values were influenced by body size, reproductive status and parasite infestations, while δ13C values were influenced by body size, oxygen conditions and survival. Using regression analysis with isotope composition and growth variables as predictors, we were able to discriminate between the amphipods exposed to nutritionally or chemically stressful conditions and those in the control groups. Thus, interpretation of isotopic niche can be confounded by natural or anthropogenic stressors that may induce an apparent change in isotopic niche. These findings stress the importance of including measures of growth and health status when evaluating stable isotope data in food web studies.


The use of anti-D prophylaxis in the management of miscarriage in general practice.
Deaths from rhesus (Rh) haemolytic disease dropped steeply after anti-D immunoglobin became available for prophylaxis in Britain in 1969. Nevertheless, Rh incompatibility remains a cause of perinatal mortality and some unregistered fetal deaths before 28 weeks gestation. Some of these deaths are attributed to a failure to administer anti-D immunoglobin in the appropriate circumstances. The prophylactic administration of anti-D immunoglobin to Rh negative women or women whose Rh type was unknown was explored as part of a survey of the management of miscarriage in general practitioner training practices in the West of Scotland. Trainees were found to be the most likely, and general practitioners who had qualified before 1970 the least likely to offer anti-D prophylaxis. The advice of the Health Departments is currently unambiguous about the need to administer anti-D immunoglobin after miscarriage. The findings described here indicate the need to implement this advice more effectively until the question of first trimester sensitisation has been resolved.


Radiofrequency volume turbinate reduction versus partial turbinectomy: clinical and histological features.
Nasal obstruction is a common symptom related to turbinate hypertrophy in 20% of cases. When medical treatment failed different surgical options were available. Actually, nasal physiology impairment after surgical treatment is not fully clear. This study evaluates microscopic mucosal changes and physiological function, by means of mucociliary transport time (MCT), after radiofrequency volume turbinate reduction and partial inferior turbinectomy. Forty-eight nonallergic patients were treated for chronic nasal obstruction. Twenty-six patients (group A) underwent radiofrequency turbinate reduction and 22 patients (group B) underwent partial turbinectomy associated with septoplasty. Mucosal specimens obtained before T(0) and 6 months (T(1)) after surgery were compared by means of optical microscope and transmission electron microscope. All patients were evaluated using MCT at T(0) and T(1). Optical analysis showed circumscribed squamous metaplasia and fibrosis in specimens obtained from group A. Same changes were more evident in group B. Ultrastructural analysis evidenced loss of ciliated epithelium in group B, whereas in group A a normal number of cilia was found. In all patients at T(1), MCT time was prolonged in comparison with the preoperative values. After surgery, group B showed significantly prolonged MCT in comparison with group A (p < 0.05). In our study both surgical techniques achieved good clinical outcomes with improved nasal function, although the ciliated epithelium appeared partially impaired. These findings resulted in a prolonged MCT in all patients, especially in those treated with partial turbinectomy. Compared to partial resection, intraturbinal turbinate reduction seems to be the method of choice to better preserve nasal physiology.


Plasmonically enhanced electron escape from gold nanoparticles and their polarization-dependent excitation transfer along DNA nanowires.
Here we show plasmon mediated excitation transfer along DNA nanowires over up to one micrometer. Apparently, an electron excitation is initiated by a femtosecond laser pulse that illuminates gold nanoparticles (AuNP) on double stranded DNA (dsDNA). The dependency of this excitation on laser wavelength and polarization are investigated. Excitation of the plasmon resonance of the AuNPs via one- and two-photon absorption at 520 and 1030 nm, respectively, was explored. We demonstrate an excitation transfer along dsDNA molecules at plasmon supported four-photon excitation of AuNP cluster or at laser field driven nanoparticle electron tunneling for an alignment of the attached dsDNA to the polarization of the electric field of the laser light. These results extend the previously observed plasmonically induced three-photon excitation transfer along DNA nanowires to another nanoparticle material (gold) and the adapted irradiation wavelengths.


The prognostic biomarkers HOXB13, IL17BR, and CHDH are regulated by estrogen in breast cancer.
We previously identified three genes, HOXB13, IL17BR, and CHDH, that strongly predict clinical outcome in estrogen receptor (ER)-positive breast cancer patients receiving tamoxifen monotherapy. The biological mechanisms linking these genes to estrogen signaling and tamoxifen response in breast cancer remain to be determined. In a consecutive series of 148 ER-positive and ER-negative breast cancers, HOXB13, IL17BR, and CHDH gene expression was measured by quantitative real-time PCR and correlated with ER, PR, and HER2 expression. The role of estrogen and ER in the regulation of these three genes was assessed in several ER-positive and ER-negative breast cancer cell lines. In primary breast tumors, HOXB13 expression correlated negatively, and IL17BR and CHDH expression correlated positively, with ER status, and all three genes exhibited an ER-dependent correlation pattern with HER2 status that differs from PR and PS2, two canonical estrogen-regulated genes. Results using breast cancer cell lines show that these genes are regulated by estradiol in an ER-dependent manner, and that this regulation is abrogated by tamoxifen. HOXB13, IL17BR, and CHDH are estrogen-regulated genes, but their pattern of correlation with known positive (ER, PR) and negative (HER2) predictors of tamoxifen response differs from canonical ER signature genes. These results provide a biological rationale for the prognostic utility of these three genes in early-stage ER-positive breast cancer and for their potential to predict anti-estrogen resistance.


Isolation and characterization of Borrelia burgdorferi from Illinois Ixodes dammini.
Ixodes dammini ticks from two northwestern Illinois sites were found to be infected with Borrelia burgdorferi at rates of 19 and 32%. B. burgdorferi isolates, one from each site, had protein and antigenic patterns similar to those of the B-31 strain. An indirect immunofluorescence method proved to be more sensitive than dark-field microscopy in detection of these spirochetes. A modified BSK medium containing rifampin was found to be more efficient for spirochete isolation than unsupplemented BSK medium.


The endoscopic evaluation of gastritis, gastric remnant residue, and the incidence of secondary cancer after pylorus-preserving and transverse gastrectomies.
Pylorus-preserving gastrectomy (PPG) and transverse gastrectomy (TrG) have been accepted as function-preserving procedures for node-negative early gastric cancer. It is believed that a better quality of life is guaranteed after PPG or TrG compared to that after distal subtotal gastrectomy (DSG) with Billroth type-I reconstruction. However, objective evaluations of the gastric remnant following gastrectomy have not been widely reported, and the real advantages and disadvantages of PPG or TrG over DSG remain unclear. Moreover, the risk of secondary cancer after PPG or TrG is uncertain. Between 1991 and 2000, 834 DSGs were carried out in our institute for preoperatively diagnosed patients with early gastric cancer. The degree of residual gastritis and the amount of diet residue in the gastric remnant were evaluated by annual gastrointestinal endoscopic investigations prospectively for 72 patients after PPG, 95 patients after TrG, and 60 patients after DSG. These analyses were performed using the RGB classification (residue, gastritis, bile). The incidence of disease greater than or equal to grade 2 was calculated, and the time trends of the incidence for each procedure were also studied for 3 years after gastrectomy. In addition, secondary cancer cases in the gastric remnant mucosa were checked for each procedure during this period, and the incidence of secondary cancer after each operation was calculated. The incidence of gastritis, of grade 2 or more, found in the gastric remnant was significantly lower after PPG (1.4%) and TrG (2.1%) than after DSG (43.3%). However, the incidence of moderate or greater residue in the gastric remnant, grade 2 or more, was significantly higher after PPG (45.8%) and TrG (40.0%) than after DSG (11.7%). The analysis of time trends of gastritis and diet residue reflected the significant advantage or disadvantage for each procedure 1 year after surgery. The analysis also included these factors without consideration of elapsed time following surgery. Two patients after PPG (2.8%) and three patients after TrG (3.2%) developed secondary cancer in the gastric remnant. No DSG-treated patient showed new cancer genesis in the remaining stomach. PPG and TrG have the advantage over DSG in preventing postoperative gastritis in the gastric remnant. On the other hand, moderate or greater diet residue in the gastric remnant is more common after PPG or TrG than after DSG. For the risk of carcinogenesis in the remnant gastric mucosa, we could not conclude that there was any apparent difference between these range-limited gastrectomies and conventional DSG. Further study is necessary to determine the significant advantages and disadvantages of using PPG or TrG.


Clara cell secretory protein (CC16): features as a peripheral lung biomarker.
Clara cell protein (CC16 or CC10) is a 15.8-kDa protein secreted all along the tracheobronchial tree and especially in the terminal bronchioles where Clara cells are localized. Even though the exact in vivo function of CC16 remains to be clarified, evidence is accumulating that CC16 plays an important protective role in the respiratory tract against oxidative stress and inflammatory response. CC16, however, presents also a major interest as a peripheral lung marker for assessing the cellular integrity or the permeability of the lung epithelium. The serum concentrations of CC16 are decreased in subjects with chronic lung damage caused by tobacco smoke and other air pollutants as a consequence of the destruction of Clara cells. By contrast, serum CC16 increases in acute or chronic lung disorders characterized by an increased airways permeability. The sensitivity of serum CC16 to an increased leakiness of the lung allows for the detection of defects of the epithelial barrier at ozone levels below current air-quality guidelines. Although the clinical significance of these early epithelial changes detected by serum CC16 remains to be determined, these results clearly show that the assay in serum of lung secretory proteins such as CC16 represents a new noninvasive approach to evaluate the integrity of the respiratory tract.


Flexible Wearable Sensors for Cardiovascular Health Monitoring.
Cardiovascular diseases account for the highest mortality globally, but recent advances in wearable technologies may potentially change how these illnesses are diagnosed and managed. In particular, continuous monitoring of cardiovascular vital signs for early intervention is highly desired. To this end, flexible wearable sensors that can be comfortably worn over long durations are gaining significant attention. In this review, advanced flexible wearable sensors for monitoring cardiovascular vital signals are outlined and discussed. Specifically, the functional materials, configurations, mechanisms, and recent advances of these flexible sensors for heart rate, blood pressure, blood oxygen saturation, and blood glucose monitoring are highlighted. Different mechanisms in bioelectric, mechano-electric, optoelectric, and ultrasonic wearable sensors are presented to monitor cardiovascular vital signs from different body locations. Present challenges, possible strategies, and future directions of these wearable sensors are also discussed. With rapid development, these flexible wearable sensors will potentially be applicable for both medical diagnosis and daily healthcare use in tackling cardiovascular diseases.


Lumbar plexus blockade reduces pain after hip arthroscopy: a prospective randomized controlled trial.
Hip arthroscopy causes moderate to severe postoperative pain. We hypothesized that performance of a lumbar plexus block (LPB) would reduce postoperative pain in the postanesthesia care unit (PACU) for patients discharged home on the day of surgery. Patients received a combined spinal epidural with IV sedation, ondansetron, and ketorolac. Half of the patients (n = 42) also underwent a single-injection bupivacaine LPB. Postoperative analgesia (PACU and after discharge) was provided with oral hydrocodone/acetaminophen (5/500 mg) and an oral nonsteroidal antiinflammatory drug. IV hydromorphone was given as needed in the PACU. The LPB reduced pain at rest in the PACU (GEE: β estimate of the mean on a 0 to 10 scale = -0.9; 95% confidence interval = -1.7 to -0.1; P = 0.037). Mean PACU pain scores at rest were reduced by the LPB from 4.2 to 3.3 (P = 0.048, 95% confidence interval for difference = 0.007-1.8; uncorrected for multiple values per patient, using independent samples t test for preliminary evaluation comparing pain between the groups). There were no statistically significant differences in PACU analgesic usage, PACU pain with movement, and patient satisfaction. No permanent adverse events occurred, but 2 LPB patients fell in the PACU bathroom, without injury. Three unplanned admissions occurred; one LPB patient was admitted for epidural spread and urinary retention. Two control patients were admitted, one for oxygen desaturation and one for pain and nausea. LPB resulted in statistically significant reductions in PACU resting pain after hip arthroscopy, but the absence of improvement in most secondary outcomes suggests that assessment of risks and benefits of LPB should be individualized.


Association between second-generation antipsychotics and newly diagnosed treated diabetes mellitus: does the effect differ by dose?
The benefits of some second-generation antipsychotics (SGAs) must be weighed against the increased risk for diabetes mellitus. This study examines whether the association between SGAs and diabetes differs by dose. Patients were ≥18 years of age from three US healthcare systems and exposed to an SGA for ≥45 days between November 1, 2002 and March 31, 2005. Patients had no evidence of diabetes before index date and no previous antipsychotic prescription filled within 3 months before index date.49,946 patients were exposed to SGAs during the study period. Person-time exposed to antipsychotic dose (categorized by tertiles for each drug) was calculated. Newly treated diabetes was identified using pharmacy data to determine patients exposed to anti-diabetic therapies. Adjusted hazard ratios for diabetes across dose tertiles of SGA were calculated using the lowest dose tertile as reference. Olanzapine exhibited a dose-dependent relationship for risk for diabetes, with elevated and progressive risk across intermediate (diabetes rate per 100 person-years = 1.9; adjusted Hazard Ratio (HR), 1.7, 95% confidence interval (CI), 1.0-3.1) and top tertile doses (diabetes rate per 100 person-years = 2.7; adjusted HR, 2.5, 95% CI, 1.4-4.5). Quetiapine and risperidone exhibited elevated risk at top dose tertile with no evidence of increased risk at intermediate dose tertile. Unlike olanzapine, quetiapine, and risperidone, neither aripiprazole nor ziprasidone were associated with risk of diabetes at any dose tertile. In this large multi-site epidemiologic study, within each drug-specific stratum, the risk of diabetes for persons exposed to olanzapine, risperidone, and quetiapine was dose-dependent and elevated at therapeutic doses. In contrast, in aripiprazole-specific and ziprasidone-specific stratum, these newer agents were not associated with an increased risk of diabetes and dose-dependent relationships were not apparent. Although, these estimates should be interpreted with caution as they are imprecise due to small numbers.