Sexual function in men older than 50 years of age: results from the health professionals follow-up study.
Although many studies have provided data on erectile dysfunction in specific settings, few studies have been large enough to precisely examine age-specific prevalence and correlates. To describe the association between age and several aspects of sexual functioning in men older than 50 years of age. Cross-sectional analysis of data from a prospective cohort study. U.S. health professionals. 31 742 men, age 53 to 90 years. Questionnaires mailed in 2000 asked about sexual function, physical activity, body weight, smoking, marital status, medical conditions, and medications. Previous biennial questionnaires since 1986 asked about date of birth, alcohol intake, and other health information. When men with prostate cancer were excluded, the age-standardized prevalence of erectile dysfunction in the previous 3 months was 33%. Many aspects of sexual function (including overall function, desire, orgasm, and overall ability) decreased sharply by decade after 50 years of age. Physical activity was associated with lower risk for erectile dysfunction (multivariable relative risk, 0.7 [95% CI, 0.6 to 0.7] for >32.6 metabolic equivalent hours of exercise per week vs. 0 to 2.7 metabolic equivalent hours of exercise per week), and obesity was associated with higher risk (relative risk, 1.3 [CI, 1.2 to 1.4] for body mass index >28.7 kg/m2 vs. <23.2 kg/m2). Smoking, alcohol consumption, and television viewing time were also associated with increased prevalence of erectile dysfunction. Men who had no chronic medical conditions and engaged in healthy behaviors had the lowest prevalence. Several modifiable health behaviors were associated with maintenance of good erectile function, even after comorbid conditions were considered. Lifestyle factors most strongly associated with erectile dysfunction were physical activity and leanness.


Cannabis Use and Consequences.
As an increasing number of states legalize cannabis use for recreational and/or medical purposes, it is increasingly important to understand the neural and cognitive consequences of recreational cannabis use in adolescent consumers. Adolescence is marked by ongoing neuromaturational processes, making this a particularly vulnerable period, particularly regarding exposure to drugs, including cannabis. This review highlights evidence from studies documenting the neural impact of cannabis use in adolescence and explores mediating factors related to cannabis use.


Treatment of type 2 diabetes mellitus by viral eradication in chronic hepatitis C: Myth or reality?
Chronic hepatitis C is a systemic disease inducing metabolic alterations leading to extrahepatic consequences. In particular, hepatitis C virus (HCV) infection seems to increase the risk of incident type 2 diabetes mellitus in predisposed individuals, independently of liver disease stage. The mechanisms through which hepatitis C induces T2DM involve direct viral effects, insulin resistance, pro-inflammatory cytokines and other immune-mediated processes. Many studies have reported the clinical consequences of type 2 diabetes mellitus on hepatitis C outcome, but very few studies have addressed the issue of microangiopathic complications among patients with hepatitis C only, who develop type 2 diabetes mellitus. Moreover, clinical trials in HCV-positive patients have reported improvement in glucose metabolism after antiviral treatment; recent studies have suggested that this metabolic amelioration might have a clinical impact on type 2 diabetes mellitus-related complications. These observations raise the question as to whether the HCV eradication may also have an impact on the future morbidity and mortality due to type 2 diabetes mellitus. The scope of this review is to summarise the current evidence linking successful antiviral treatment and the prevention of type 2 diabetes mellitus and its complications in hepatitis C-infected patients.


Reversing the trend of resistant infections.
Set up alerts for at-risk patients. With antibiotic trend patterns, cost per admission in terms of antibiotics dropped 10%. Narrowing coverage in using antibiotics critical.


Hormonal influence on the secretory immune system of the eye: endocrine impact on the lacrimal gland accumulation and secretion of IgA and IgG.
The objective of the current investigation was to explore the processes underlying the androgen control of tear IgA and to determine whether hormone exposure also modifies tear IgG content. In addition, studies evaluated the impact of diabetes on the androgen regulation of secretory immunity in the eye. Tears and lacrimal glands were collected from age-matched, adult male rats, which had undergone hypophysectomy, selective ablation of the anterior pituitary, streptozotocin-induced diabetes, sham-surgery and/or orchiectomy and had been exposed to vehicle or physiological amounts of testosterone for varying periods of time. Our findings demonstrated that testosterone administration selectively increased the accumulation of IgA, but not IgG, in tears and lacrimal glands of orchiectomized rats. This hormone effect was associated with a 2-fold enhancement of the IgA transfer from lacrimal tissue to tears; IgA movement was against a gradient. In contrast, androgen exposure had no significant influence on the lacrimal gland/tear transfer of IgG, which was down a 90-fold gradient. Testosterone action on the lacrimal gland appeared to involve an increase in IgA production, but not a consistent alteration in the total number of IgA-containing cells. Similarly, androgen exposure had no impact on the population of IgG-containing lymphocytes in lacrimal tissue. Of interest, ablation of the anterior or entire pituitary in orchiectomized rats, which procedure inhibits testosterone-induced stimulation of tear IgA levels, significantly reduced the total number of IgA-containing cells in the lacrimal gland. Induction of diabetes by streptozotocin injection to orchiectomized rats resulted in diminished tear IgA content and decreased numbers of lacrimal IgA-positive lymphocytes, but did not prevent the testosterone-associated rise in IgA antibody content. In summary, our findings demonstrate that androgens increase the lacrimal gland production and secretion of IgA, but not IgG.


Integrated personalized diabetes management improves glycemic control in patients with insulin-treated type 2 diabetes: Results of the PDM-ProValue study program.
Globally, many patients with insulin-treated type-2 diabetes are suboptimally controlled. The PDM-ProValue study program evaluated whether integrated personalized diabetes management (iPDM) has the potential to improve clinical outcomes. 101 practices with 907 patients participated in the 12-month, prospective, controlled, cluster-randomized study program. HbA1c levels, therapy changes, frequency of hypoglycemic episodes, patient reported outcomes, and physician satisfaction were assessed. iPDM led to a greater reduction in HbA1c after 12 months vs. usual care (-0.5%, p < 0.0001 vs. -0.3%, p < 0.0001), (Diff. 0.2%, p = 0.0324). Most of the HbA1c reduction occurred after 3 months and remained stable thereafter. The percentage of patients with therapy adjustments was higher in the iPDM group at all visits (p < 0.01 at week 3, month 3, month 6). Patient adherence at month 12 was higher in the iPDM group compared to baseline (Odds ratio = 2.39; p = 0.0003); also, patient treatment satisfaction (DTSQc: 12.2 vs. 10.4, δ = 1.78, p = 0.004; DTSQs: 31.0 vs. 30.0, δ = 0.924, p = 0.02), and physician satisfaction was higher in the intervention group. iPDM improved the use of diagnostic data leading to better glycemic control, more timely treatment adjustments (indicating reduced clinical inertia), and increased patient adherence and treatment satisfaction among patients and physicians.


Skeletal muscle protein turnover responses to parenteral nutrition in patients with alcoholic liver cirrhosis and sarcopenia.
Alcoholic liver cirrhosis (ALC) is accompanied by sarcopenia. The aim of this study was to investigate the acute effects of balanced parenteral nutrition (PN) on skeletal muscle protein turnover in ALC. Eight male patients with ALC and seven age- and sex-matched healthy controls were studied for 3 h of fasting followed by 3 h of intravenous PN (SmofKabiven 1,206 mL: amino acid = 38 g, carbohydrates = 85 g, and fat = 34 g) 4 mL/kg/h. We measured leg blood flow and sampled paired femoral arteriovenous concentrations and quadriceps muscle biopsies while providing a primed continuous infusion of [ring-2d5]-phenylalanine to quantify muscle protein synthesis and breakdown. Patients with ALC exhibited shorter 6-min walking distance (ALC: 487 ± 38 vs. controls: 722 ± 14 m, P < 0.05), lower hand-grip strength (ALC: 34 ± 2 vs. controls: 52 ± 2 kg, P < 0.05), and computed tomography (CT)-verified leg muscle loss (ALC: 5,922 ± 246 vs. controls: 8,110 ± 345 mm2, P < 0.05). Net leg muscle phenylalanine uptake changed from negative (muscle loss) during fasting to positive (muscle gain) in response to PN (ALC: -0.18 ± +0.01 vs. 0.24 ± 0.03 µmol/kg muscle·min-1; P < 0.001 and controls: -0.15 ± 0.01 vs. 0.09 ± 0.01 µmol/kg muscle·min-1; P < 0.001) but with higher net muscle phenylalanine uptake in ALC than controls (P < 0.001). Insulin concentrations were substantially higher in patients with ALC during PN. Our results suggest a higher net muscle phenylalanine uptake during a single infusion of PN in stable patients with ALC with sarcopenia compared with healthy controls.NEW & NOTEWORTHY Muscle protein turnover responses to parenteral nutritional (PN) supplementation have not previously been studied in stable alcoholic liver cirrhosis (ALC). We applied stable isotope tracers of amino acids to directly quantify net muscle protein turnover responses to PN in sarcopenic males with ALC and healthy controls. We found a higher net muscle protein gain in ALC during PN, thereby providing the physiological rationale for future clinical trials of PN as a potential countermeasure to sarcopenia.


Energy-minimized structures and packing states of a homologous series of mixed-chain phosphatidylcholines: a molecular mechanics study on the diglyceride moieties.
Phosphatidylcholines or C(X):C(Y)PC, quantitatively the most abundant lipids in animal cell membranes, are structurally composed of two parts: a headgroup and a diglyceride. The diglyceride moiety consists of the glycerol backbone and two acyl chains. It is the wide diversity of the acyl chains, or the large variations in X and Y in C(X):C(Y)PC, that makes the family of phosphatidylcholines an extremely complex mixture of different molecular species. Since most of the physical properties of phospholipids with the same headgroup depend strongly on the structures of the lipid acyl chains, the energy-minimized structure and steric energy of each diglyceride moiety of a series of 14 molecular species of phosphatidylcholines with molecular weights identical to that of dimyristoylphosphatidylcholine without the headgroup are determined in this communication by molecular mechanics (MM) calculations. Results of two types of trans-bilayer dimer for each of the 14 molecular species of phosphatidylcholines are also presented; specifically, the dimeric structures are constructed initially based on the partially interdigitated and mixed interdigitated packing motifs followed subsequently by the energy-minimized refinement with MM calculations. Finally, tetramers with various structures to model the lateral lipid-lipid interactions in a lipid bilayer are considered. Results of laborious MM calculations show that saturated diacyl C(X):C(Y)PC with delta C/CL values greater than 0.41 prefer topologically to assemble into tetramers of the mixed interdigitated motif, and those with delta C/CL values less than 0.41 prefer to assemble into tetramers with a repertoire of the partially interdigitated motif. Here, delta C/CL, a lipid asymmetry parameter, is defined as the normalized acyl chain length difference between the sn-1 and sn-2 acyl chains for a C(X):C(Y)PC molecule; an increase in delta C/CL value is an indication of increasing asymmetry between the two lipid acyl chains. These computational results are in complete accord with the calorimetric data presented previously from this laboratory (H-n. Lin, Z-q. Wang, and C. Huang. 1991. Biochim. Biophys. Acta. 1067:17-28).


Effect of DiscoGel treatment of the intervertebral disc at MRI.
To determine the impact of ethanol gel chemonucleolysis (EGCh) on the radiological picture of the treated intervertebral disc, the relationship between the initial radiological status and the clinical status of the patient after EGCh treatment, and the optimal radiographic criteria for qualifying a patient for EGCh treatment. The study involved a group of 45 patients (25 men and 20 women) aged 23-68 years (46 ± 11) who underwent an EGCh procedure after qualification, radiography, and clinical questionnaire evaluation. The results showed a decrease in the size of the protrusion and Gadolinium-Enhanced (GI) zone in the treated intervertebral disc. The presence of a high-intensity zone (HIZ) on baseline magnetic resonance imaging was found to be a good predictor of the timing and outcome of treatment, and an increase in disc height was observed in adjacent segments. These findings suggest that EGCh is a promising treatment for spine diseases, and the HIZ on baseline magnetic resonance imaging can be used as a qualification criterion for this procedure.


Solid-state NMR spectroscopy as a tool supporting optimization of MALDI-TOF MS analysis of polylactides.
We report systematic structural studies of poly(l-lactide) (PLLA) employing matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and solid-state NMR spectroscopy. (13)C cross polarization magic angle spinning (CP/MAS) NMR data for 1,8-dihydroxy-9-anthracenone (DT), 2,5-dihydroxybenzoic acid (DHB), 2-(4-hydroxyphenylazo)-benzoic acid (HABA), and trans-3-indoleacrylic acid (IAA), four matrices commonly used in MALDI-TOF analysis of polymers, were analyzed to test the influence of crystallization conditions (solvent, inorganic salt) on sample morphology. (13)C principal elements of chemical shift tensor (CST) and line-shape analyses were employed to study of the nature of hydrogen bonding and to evaluate the crystallinity and amorphicity of the pure polymer. NMR parameters for PLLA were compared with data for polylactide crystallized with the four matrices under different conditions with the addition of two inorganic salts as cationization agents. This study revealed that the semicrystalline structure of the polymer does not change when it is embedded in the matrix.


Occurrence and trophic transfer of per- and polyfluoroalkyl substances in an Antarctic ecosystem.
Information on the occurrence and trophodynamics of per- and polyfluoroalkyl substances (PFASs) in the Antarctic region is limited. We investigated the occurrence of PFASs in an ecosystem in the Fildes Peninsula at King George Island and Ardley Island, Antarctica. The profiles, spatial distribution, and trophic transfer behavior of PFASs were further studied. ∑PFASs ranged from 0.50 ± 38.0 ng/g dw (dry weight) in algae to 4.97 ± 1.17 ng/g dw in Neogastropoda (Ngas), which was lower than those in the low- and mid-latitude regions and even Arctic regions. Perfluorobutyric acid (PFBA) was predominant with detection frequencies above 50% in all types of samples, and the relative contribution of PFBA ranged from 22% to 57% in the biota samples. The biomagnification factors of PFBA, perfluoroheptanoate (PFHpA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) between Archaeogastropoda (Agas) and Ngas were 0.67 ± 0.54, 0.77 ± 0.38, 1.04 ± 1.56, 3.30 ± 4.07, and 1.61 ± 0.89, respectively. The trophic magnification factors of PFHxS and PFOS were 2.09 and 2.92, respectively, which indicated that they could be biomagnified through the food chain. Considering the increasing production and uncertain toxicological risks of emerging PFASs and the sensitive ecosystems in Antarctic regions, more attention should be paid, especially for the short-chain ones in the Antarctic region.


Concurrent detection of cholecystocolic fistula and hepatic abscess by hepatobiliary scintigraphy.
We report the case of a 58-year-old male with cholecystocolic fistula and hepatic abscess that were not diagnosed by routine radiologic examinations, but concurrently detected by hepatobiliary scintigraphy with 99mTc-PMT, and confirmed at operation. Hepatobiliary scintigraphy is noninvasive and useful in the detection of a biliary enteric fistula and lesions about related organs. Concurrent detection of cholecystocolic fistula and hepatic abscess on hepatobiliary series is of great clinical value in planning surgical intervention.


Three Days of Chronic Intermittent Hypoxia Induce β1-Adrenoceptor Dependent Increases in Left Ventricular Contractility.
Sleep apnea is characterized by bouts of chronic intermittent hypoxia (CIH) that elicit sympathetic hyperactivity resulting in residual hypertension. We previously demonstrated that exposure to CIH increases cardiac output and sought to determine if enhanced cardiac contractility manifests prior to hypertension.Male Wistar rats were exposed to cyclical bouts of hypoxia (FiO2 = 0.05 nadir; 90 s) and normoxia (FiO2 = 0.21; 210 s) 8 h/day for 3 days (CIH; n = 6). Control animals (n = 7) were exposed to room air. Data are presented as mean ± SD and were analyzed using unpaired Student t-tests.Three-day exposure to CIH did not elicit changes in heart rate and blood pressure (p > 0.05). However, baseline left ventricular contractility (dP/dtMAX) was significantly increased in CIH-exposed animals compared with control (15300 ± 2002 vs. 12320 ± 2725 mmHg/s; p = 0.025), despite no difference in catecholamine concentrations. Acute β1-adrenoceptor inhibition reduced contractility in CIH-exposed animals (-7604 ± 1298 vs. -4747 ± 2080 mmHg/s; p = 0.014), to levels equivalent to control, while preserving cardiovascular parameters. Sympathetic ganglion blockade (hexamethonium 25 mg/kg; i.v.) produced equivalent cardiovascular responses suggesting similar global sympathetic activity between groups. Interestingly, gene expression of the β1-adrenoceptor pathway in cardiac tissue was unchanged.Our results suggest that CIH increases cardiac contractility via β1-adrenoceptor dependent mechanisms prior to development of global sympathetic hyperactivity suggesting that positive cardiac inotropy contributes to the development of hypertension in CIH-exposed rats.


The hippocampus as a common target of neurotoxic agents.
The hippocampus (HPC) is in a strategic position to process information derived from the polymodal association areas of the neocortex and to redistribute it to cortical and subcortical regions involved in the modulation of complex behavioral processes. Several converging lines of evidence indicate that the HPC and its cholinergic input are an important neurobiological substrate for learning and memory processes. Destruction of the HPC proper, its afferent projections, and its cholinergic innervation, produces a persistent impairment in cognitive function. Since alterations in learning and memory are a common consequence of toxicant exposure it is possible that the HPC is an important target site for neurotoxicity. In fact, the HPC has been shown to be preferentially susceptible to a wide variety of toxic insults and disease states. For example, the HPC is damaged by a number of environmental toxicants (heavy metals and their alkyl derivatives), metabolic perturbations, neuroactive viruses, cerebrovascular insufficiency, and neurodegenerative diseases. The susceptibility of this structure to a broad spectrum of insults and its involvement in higher order cognitive processes makes it an important focal point for studies of behavioral and neurological toxicity. Neurobiological characteristics of the HPC that might make this structure uniquely susceptible to toxic insult are discussed.


Association between perfluorinated compounds and time to pregnancy in a prospective cohort of Danish couples attempting to conceive.
Perfluorinated chemicals (PFCs) have been widely used and have emerged as important food contaminants. A recent study on pregnant women suggested that PFC exposure was associated with a longer time to pregnancy (TTP). We examined the association between serum concentrations of PFCs in females and TTP in 222 Danish first-time pregnancy planners during the years 1992-1995. The couples were enrolled in the study when discontinuing birth control and followed for six menstrual cycles or until a clinically recognized pregnancy occurred. Fecundability ratio (FR) was calculated using discrete-time survival models. In addition, odds ratio (OR) for TTP >6 cycles was calculated. OR for TTP >6 cycles for those with PFC concentrations above the median were 0.96 [95% confidence interval (CI): 0.54-1.64] for perfluorooctane sulfonic acid (PFOS), the major PFC, compared with those below the median. FRs for those with PFOS concentrations above the median were 1.05 (95% CI: 0.74-1.48) compared with those below the median. Other PFCs showed the same lack of association with TTP. The results were not affected by adjustment for covariates. PFOS and perfluorooctanoic acid concentrations were similar to those observed in a previous Danish study. These findings suggest that exposure to PFCs affects TTP only to a small extent, if at all.


Autonomic neural control of liver glycogen metabolism.
Neural and humoral induction of hepatic glycogenolysis occurs via different pathways. Sympathetic nerve stimulation activates alpha adrenergic receptors to produce what is probably a cyclic AMP independent, Ca++ dependent activation of glycogen phosphorylase. Evidence suggests that phosphorylase 'a' is activated by inhibition of phosphorylase phosphatase and perhaps by activation of phosphorylase kinase. Blood borne catecholamines act via beta adrenergic receptors to produce a cyclic AMP dependent activation of phosphorylase kinase. Additionally, hepatic parasympathetic nerves can produce a dramatic shut-down of hepatic glucose output by activation of glycogen synthetase and inhibition of glycogen phosphorylase. The observed minor effect of insulin or intravenous glucose on hepatic glucose uptake compared to the effect of oral doses of glucose suggests that an additional factor other than insulin can produce hepatic glucose uptake: this factor could be, and probably is, the hepatic parasympathetic nerves. The present hypotheses result from a combination and extrapolation of whole animal physiological and in vitro biochemical data.


Phenotypic and cytolytic activity of Macaca nemestrina natural killer cells isolated from blood and expanded in vitro.
Natural killer (NK) cells from nonhuman primates have not been completely characterized, and methods for expanding nonhuman primates NK cells in vitro have been described only in rhesus species. The purpose of this report was to characterize NK cells in pigtail macaques (Macaca nemestrina), a species that is frequently used in studies of transplantation biology/immunology, virology, vaccine development, and reproductive biology. NK cells from Macaca nemestrina peripheral blood were best defined by the expression of CD16 and CD8alpha, and the absence of CD3. Subsets of these cells express CD56, NKp30, and NKp46. An enhanced ability to kill K562 cells was not present in fluorescence activated cell sorted (FACS)-purified CD16-/CD3+ and CD16-/CD56+ cells isolated from fresh peripheral blood. However, FACS-purified CD16+/CD3- and CD16+/CD56- cells were highly efficient killers of K562 cells. Macaca nemestrina NK cells can be expanded by in vitro culturing of FACS-purified CD16+/CD2-/CD3-/CD56- cells, or from peripheral blood cells depleted of cells expressing CD3, CD4, and HLA-DR. Cells in these cultures expand 70-fold after 21 days of culturing. After culturing, these cells express high levels of natural cytotoxicity receptors (NCRs) NKp30 and NKp46. NK cell populations obtained from FACS-purified CD16+/CD3-, CD16+/CD56- cells and CD3/CD4/HLA-DR-depleted cells were highly efficient killers of K562 cells. These data suggest that a population of highly enriched cytolytic NK cells can be obtained from purified CD16+/CD3- and CD16+/CD56- cells obtained from peripheral blood, as well as from cells that have been cultured and expanded from peripheral blood that is depleted of CD3/CD4/HLA-DR-expressing cells.


Is dopamine a neurohormone of the adrenal medulla? Studies with morphine stimulation.
Dopamine (da) concentrations in rat adrenals, plasma and brain were variably elevated 1 h after a large parenteral dose of morphine. In adrenals, unlabelled DA increased 2-fold and labelled DA, synthesized from 3H-tyrosine, increased more than 4-fold. The increases could be prevented by inhibition of DA-synthesizing enzymes and spinal cord transection, respectively. Labelled DA in plasma increased 2.7-fold after morphine in intact rats but did not increase in those with spinal cord transection. It is concluded that: (1) morphine stimulates the adrenal by increasing nerve impulse flow, (2) increased nerve impulse flow increases DA synthesis and levels, and (3) the increased DA levels result in increased release of DA into the bloodstream.


Increased inspiratory pressure for reduction of atelectasis in children anesthetized for CT scan.
Atelectasis is more frequent and more severe in children anesthetized for CT scan than it is in children sedated for CT scan. To determine the effect of increased inspiratory pressure on atelectasis during chest CT in anesthetized children. Atelectasis on chest CT was assessed by two observers in three groups of patients. Group A comprised 13 children (26 lungs) anesthetized at inspiratory pressures up to and including 25 cm H2O. Group B included 11 children anesthetized at inspiratory pressures > or =30 cm H2O. Group C included 8 children under deep sedation. Atelectasis was significantly more severe in group A than in groups B and C. There was no significant difference between groups B and C. An inspiratory pressure of 30 cm H2O is recommended for children anesthetized for CT scan of the chest.


Volvulus of the sigmoid colon.
The clinical presentation and treatment of 31 consecutive patients with sigmoid volvulus are reviewed. Nearly half of these patients had a history of mental illness and one-third of all patients were chronically constipated. The main clinical features of abdominal pain and gross abdominal distension had been present for an average of 8 days before presentation of the patient to hospital. The clinical diagnosis of sigmoid volvulus was not difficult but the presence of non-viable bowel was more difficult to establish. A silent abdomen was the most valuable indication of the presence of gangrenous bowel. Conservative measures, including sigmoidoscopy and therapeutic barium enema, successfully reduced the volvulus in half of the cases so treated. In those patients undergoing surgery the procedure associated with the lowest mortality was sigmoid resection with end-to-end anastomosis. The overall mortality was 35%.


Using photovoice to understand and improve healthy lifestyles of people diagnosed with serious mental illness.
WHAT IS KNOWN ON THE SUBJECT?: People diagnosed with serious mental illness (SMI): Live 10 to 20 years less than the general population, and this can be related to lifestyle factors such as poor diet and low levels of physical activity. Have a good understanding of what healthy lifestyle comprises of, but face barriers and challenges related to their mental health, treatment, and life situation. There is limited participatory research that considers the specific beliefs of people diagnosed with SMI about what "being healthy" means to them. People diagnosed with SMI value health and are often already engaged in activities that promote both physical and mental health. They experience the "vicious cycle" of barriers to engage in healthier lifestyle, including medication effects, poor sleep routines, fatigue, low mood and establishing a routine, but this shows how healthy activities can improve their mental health. The importance of meaningful places and their role in supporting healthy lifestyles was identified Some people diagnosed with SMI face significant socio-economic challenges (such as lack of cooking facilities; limited money for purchasing healthy food) to support healthy lifestyles. To truly understand the perspectives of people with SMI, who are typically voiceless and disempowered, research methods need to allow the participants to set the agenda for discussion, to not only provide rich data but also have the added benefit of empowerment and enhanced engagement. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Mental health nurses should: Explore the practical barriers to healthy lifestyle such as financial concerns and ensure that people can access support to obtain what they need from the local community resources. Instigate a mental health and/or medication review if mental health symptoms or medication side effects are a barrier to healthy lifestyles Explore what places have meaning and consider how to use meaningful places as motivating factors for healthy lifestyles and promoting mental well being. INTRODUCTION: People diagnosed with serious mental illness (SMI) live 10-20 years less than the general population, due in part to co-existing physical illness linked to lifestyle factors. To inform individualized care plans to promote healthy lifestyles, it is important to understand the views of people diagnosed with SMI. To truly understand their lived experience, research methods should allow participants to set the agenda for discussion, enhancing engagement and empowerment in the research process. To use a participatory research approach to capture what healthy lifestyle means to people who are diagnosed with SMI. Eight people diagnosed with SMI participated in six, weekly focus groups using Photovoice. Data were analysed using thematic analysis. The overarching theme was 'mental health is the main priority', and the other themes were barriers to a healthy lifestyle, represented as a vicious cycle, and three themes, which were facilitators - the importance of place, meaningful activities, and the importance of others. The methodology allowed participants to choose images that reflected their lived experience. The themes describe the interaction of physical and mental health and practical barriers and will inform the design of individualized care plans. In co-designing care plans, mental health nurses should draw on peoples' preferences and explore the barriers identified in this study.


Investigation of the transverse topology of the microsomal membrane using combinations of proteases and the non-penetrating reagent diazobenzene sulfonate.
Intact microsomal vesicles from rat liver were subjected to combined treatment with trypsin and an unspecific protease and were also examined after reaction with the chemical probe p-diazobenzene sulfonate. In addition, the latency of various enzymes in intact microsomal vesicles has been investigated. All microsomal electron transport enzymes studied, i.e. NADH-ferricyanide and cytochrome c reductases, cytochrome b5, NADPH-cytochrome c reductase and cytochrome P-450, were either solubilized or inactivated by one or both treatments. The experimental data indicate that UDPglucuronyl-transferase is also localized at the outer surface of microsomes. In contrast, a number of hydrolytic enzymes are apparently located inside the permeability barrier of the membrane and presumably at the inner surface. Under conditions where the levels of electron transport enzyme activities or amounts are changed, such as in newborn rats and rats treated with phenobarbital or methylcholanthrene, the intramembranous position of these enzymes is the same as in control adult rats. This indicates that the enzyme molecules are not relocated after their insertion into the membrane.


A Novel Katanin-Tethering Machinery Accelerates Cytokinesis.
Cytokinesis is fundamental for cell proliferation [1, 2]. In plants, a bipolar short-microtubule array forms the phragmoplast, which mediates vesicle transport to the midzone and guides the formation of cell walls that separate the mother cell into two daughter cells [2]. The phragmoplast centrifugally expands toward the cell cortex to guide cell-plate formation at the cortical division site [3, 4]. Several proteins in the phragmoplast midzone facilitate the anti-parallel bundling of microtubules and vesicle accumulation [5]. However, the mechanisms by which short microtubules are maintained during phragmoplast development, in particular, the behavior of microtubules at the distal zone of phragmoplasts, are poorly understood. Here, we show that a plant-specific protein, CORTICAL MICROTUBULE DISORDERING 4 (CORD4), tethers the conserved microtubule-severing protein katanin to facilitate formation of the short-microtubule array in phragmoplasts. CORD4 was specifically expressed during mitosis and localized to preprophase bands and phragmoplast microtubules. Custom-made two-photon spinning disk confocal microscopy revealed that CORD4 rapidly localized to microtubules in the distal phragmoplast zone during phragmoplast assembly at late anaphase and persisted throughout phragmoplast expansion. Loss of CORD4 caused abnormally long and oblique phragmoplast microtubules and slow expansion of phragmoplasts. The p60 katanin subunit, KTN1, localized to the distal phragmoplast zone in a CORD4-dependent manner. These results suggest that CORD4 tethers KTN1 at phragmoplasts to modulate microtubule length, thereby accelerating phragmoplast growth. This reveals the presence of a distinct machinery to accelerate cytokinesis by regulating the action of katanin.


Expression of beta 1-6-branched N-linked oligosaccharides is associated with activation in human T4 and T8 cell populations.
Activation of human T lymphocytes by phorbol 12-myristate 13-acetate and leukoagglutinin from Phaseolus vulgaris (L-PHA) results in important changes in N-glycosylation. The most important event is the increase, in both T4 and T8 cells (especially the latter), of L-PHA+ structures characterized by beta 1-6-branching of complex-type oligosaccharides. Moreover, the existence of a CD4-mediated increase of these beta 1-6-branched structures on positively selected T4 cells, as compared with the negatively selected ones, suggests that the presence of these structures, not detectable on T8 resting cells, could be related to stimulation events triggered by both selection methods. This beta 1-6-branching on N-glycans, strongly associated with a metastatic phenotype in human and rodent tumors, is exhibited by numerous glycoproteins on stimulated cells, as shown by blot analysis.


Cyberbullying in Adolescents: Resilience as a Protective Factor of Mental Health Outcomes.
The present cross-sectional research examined the moderating role of resilience in the relationship between cyberbullying victimization and mental health outcomes, measured based on depression symptoms and life satisfaction. The sample consisted of 2,108 adolescents aged 12-17 who completed measures of cyberbullying victimization, resilience, depression, and life satisfaction. Structural equation models showed an appropriate fit of the moderation model of resilience in the relationship between cyberbullying victimization and mental health outcomes [χ2 (149) = 1,270.368; root-mean-squared error of approximation = 0.066; comparative fit index = 0.923; Tucker-Lewis index = 0.907]. Regression analyses revealed significant interaction effects, indicating that among adolescents with high levels of resilience, cyberbullying victimization was associated with fewer symptoms of depression and a smaller reduction in life satisfaction. This study highlights the importance of working on resilience in adolescents as a mechanism to deal with cyberbullying victimization.


Sequence-specific RNA Photocleavage by Single-stranded DNA in Presence of Riboflavin.
Constant efforts have been made to develop new method to realize sequence-specific RNA degradation, which could cause inhibition of the expression of targeted gene. Herein, by using an unmodified short DNA oligonucleotide for sequence recognition and endogenic small molecule, vitamin B2 (riboflavin) as photosensitizer, we report a simple strategy to realize the sequence-specific photocleavage of targeted RNA. The DNA strand is complimentary to the target sequence to form DNA/RNA duplex containing a G • U wobble in the middle. The cleavage reaction goes through oxidative elimination mechanism at the nucleoside downstream of U of the G • U wobble in duplex to obtain unnatural RNA terminal, and the whole process is under tight control by using light as switch, which means the cleavage could be carried out according to specific spatial and temporal requirements. The biocompatibility of this method makes the DNA strand in combination with riboflavin a promising molecular tool for RNA manipulation.


Iron encapsulated in boron and nitrogen codoped carbon nanotubes as synergistic catalysts for Fenton-like reaction.
Iron nanoparticles (NPs) encapsulated in B, N-codoped carbon nanotubes (Fe@C-BN) as heterogeneous Fenton-like catalysts were obtained by a simple and scalable pyrolysis method, and their performances were examined in the oxidative degradation of various organics in the presence of the different oxidants. The results showed that organic dyes can be effectively degraded by Fe@C-BN in the presence of peroxymonosulfate. Calcination temperature and mass of iron salt significantly affected the structures and performances of the catalysts. The effects of several reaction conditions, such as initial dye concentration, oxidant type (peroxymonosulfate, peroxydisulfate, and H2O2) and dosage, initial pH, inorganic anions, reaction temperature and dye types on oxidation as well as the stability of the composite were extensively evaluated in view of the practical applications. Through the investigation of reaction processes, HO(·) and SO4(·-) radicals were identified using quenching experiments. Owing to the synergistic effects between the iron NPs and B, N-doped carbon, Fe@C-BN catalysts intrinsically display an excellent catalytic activity for Fenton-like reaction. This study gives new insights into the design and preparation of iron NPs encapsulated in B, N-codoped carbon nanotubes as an effective strategy to enhance the overall catalytic activity.


[Obstructive jaundice caused by Ascaris lumbricoides].
In middle Europe biliary complications caused by Ascaris lumbricoides are very rare. We report on endoscopic removal of an Ascaris out of the common bile duct in a 81-years-old woman.


Augmentation of postresection mucosal hyperplasia by plerocercoid growth factor (PGF). Analog of human growth hormone.
Postresection villus hyperplasia is a major compensatory mechanism in the short-bowel patient. Substances capable of augmenting postresection mucosal hyperplasia could have therapeutic implications. Human growth hormone (hGH) and human growth hormone releasing factor (hGHRF) stimulate growth of the gastrointestinal tract; however, the diabetogenic actions of growth hormone limit its usefulness in clinical practice. Plerocercoid larvae of the tapeworm Spirometra mansonoides produce an analog of hGH void of diabetogenic side effects. We assessed effects of plerocercoid growth factor (PGF) on mucosal adaptation following 70% proximal jejunoileal resection in young rats. Mucosal weight, DNA, protein, and total sucrase activity per centimeter of bowel were increased in resected PGF-treated animals compared to resected controls. We conclude PGF augments intrinsic postresection mucosal hyperplasia following extensive intestinal resection.


Unrelated donor marrow transplantation for B-cell chronic lymphocytic leukemia after using myeloablative conditioning: results from the Center for International Blood and Marrow Transplant research.
To determine the role of myeloablative conditioning and unrelated donor (URD) bone marrow transplantation in the treatment of patients with advanced B-cell chronic lymphocytic leukemia (CLL). A total of 38 CLL patients received a matched URD transplant using bone marrow procured by the National Marrow Donor Program. The median age was 45 years (range, 26 to 57 years), the median time from diagnosis was 51 months, and the median number of prior chemotherapy regimens was three. Fifty-five percent of patients were chemotherapy refractory and 89% had received fludarabine. Conditioning included total-body irradiation in 92% of patients. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate with cyclosporine or tacrolimus for 82% of patients. Twenty-one patients (58%) achieved complete response and six (17%) achieved partial response. Incidences of grades 2 to 4 acute GVHD were 45% at 100 days and incidences of chronic GVHD were 85% at 5 years. Eleven patients are alive and disease free at a median of 6 years (range, 3.0 to 9.0 years). Five-year overall survival, failure-free survival, disease progression rates, and treatment-related mortality (TRM) were 33%, 30%, 32%, and 38% respectively. These data demonstrate that lasting remissions can be achieved after URD transplantation in patients with advanced CLL. High TRM suggest that myeloablative conditioning and HLA-mismatched donors should be avoided in future protocols, and it is mandatory to investigate transplant strategies with a lower morbidity and mortality, including the use of nonmyeloablative regimens.


Surgical Treatment of the Middle Nasal Vault.
The middle nasal vault is a sensitive region of the nose from both an esthetic and a functional perspective. It is critical for the rhinoplasty surgeon to properly evaluate and identify abnormalities of the middle vault when considering patients for primary or secondary surgery. This article addresses the surgical management of the cosmetic deformities and functional deficits of the middle vault and provides guidance for avoiding complications in this structurally critical region of the nose.


Considerations of management and marketing courses within pharmacy curricula in the United States.
To assess the extent pharmacy programs are offering courses in management and marketing. We sampled the extent of management and marketing coursework in the doctor of pharmacy (PharmD) curricula in the United States (US) by examining website descriptions of the best pharmacy schools in 2020 (N = 134) as ranked by the US News and World report. Links to curriculum descriptions and catalogs were reviewed for coursework having the words, marketing, management, entrepreneurship, or business plan in the title. Of the 134 PharmD curricula reviewed, 36 (27%) had no required or elective management courses, and 101 (75%) had no required or elective marketing courses in their curriculum. Most schools did offer a core (n = 89) or elective (n = 9) management course. However, of those, about half (n = 46) provided only a single management course over the entire curriculum. Only 33 (25%) schools offered a marketing course, of which most (n = 27) were elective. Many pharmacy schools in the US are not providing pharmacy graduates with the business management and marketing education required for the role of a pharmacist. Pharmacy education should consider curriculum changes that equip pharmacy students with sufficient business knowledge and skills to be innovative and entrepreneurial in all practice settings.


Targeted deletion of von-Hippel-Lindau in the proximal tubule conditions the kidney against early diabetic kidney disease.
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Glomerular hyperfiltration and albuminuria subject the proximal tubule (PT) to a subsequent elevation of workload, growth, and hypoxia. Hypoxia plays an ambiguous role in the development and progression of DKD and shall be clarified in our study. PT-von-Hippel-Lindau (Vhl)-deleted mouse model in combination with streptozotocin (STZ)-induced type I diabetes mellitus (DM) was phenotyped. In contrary to PT-Vhl-deleted STZ-induced type 1 DM mice, proteinuria and glomerular hyperfiltration occurred in diabetic control mice the latter due to higher nitric oxide synthase 1 and sodium and glucose transporter expression. PT Vhl deletion and DKD share common alterations in gene expression profiles, including glomerular and tubular morphology, and tubular transport and metabolism. Compared to diabetic control mice, the most significantly altered in PT Vhl-deleted STZ-induced type 1 DM mice were Ldc-1, regulating cellular oxygen consumption rate, and Zbtb16, inhibiting autophagy. Alignment of altered genes in heat maps uncovered that Vhl deletion prior to STZ-induced DM preconditioned the kidney against DKD. HIF-1α stabilization leading to histone modification and chromatin remodeling resets most genes altered upon DKD towards the control level. These data demonstrate that PT HIF-1α stabilization is a hallmark of early DKD and that targeting hypoxia prior to the onset of type 1 DM normalizes renal cell homeostasis and prevents DKD development.


Photobiomodulation therapy as a high potential treatment modality for COVID-19.
COVID-19 is now a worldwide concern, causing an unprecedented pandemic. The infected cases show different symptoms based on the severity of the disease. In asymptomatic and non-severe symptomatic cases, the host immune system can successfully eliminate the virus and its effects. In severe cases, however, immune system impairment causes cytokine release syndrome which eventually leads to acute respiratory distress syndrome (ARDS). In recent years, photobiomodulation (PBM) has shown promising results in reducing acute pulmonary inflammation. Considering the high potential impact of PBM on immune responses, we hypothesized that using PBM could be an effective treatment modality for ARDS management in COVID-19 patients.


[Activity of antioxidant enzymes and intensity of free radical oxidation processes in swine tissues during postnatal adaptation].
It was studied the activity of superoxide dismutase, glutathione peroxidase, glutathione reductase, and contents of malondialdehyde and hydroperoxide lipids in the tissues of skeletal muscles, heart, lungs, testicles in the piglets of 1-, 3-, 5- and 10-days age. It was found, that tissues of 1-days piglets characterized by high contents of products of hydroperoxide lipids and activity of superoxide dismutase by low activity of glutathione peroxidase and glutathione reductase. The products contents of hydroperoxide lipids in piglets tissues in the period of 1 to 10-days age reduced. The activity of enzymes of antioxidant system depends from stage of postnatal adaptation and from the kinds of tissues.


The synovial prostaglandin system in chronic inflammatory arthritis: differential effects of steroidal and nonsteroidal anti-inflammatory drugs.
1 The present study was undertaken to characterize the spectrum of arachidonic acid metabolites present in synovial effusions of patients with rheumatoid or psoriatic arthritis, and to compare changes in their concentration following a short-term treatment with 6alpha-methyl-prednisolone (6-MeP: 4-8 mg/day) or indoprofen (1.2 g/day), a nonsteroidal anti-inflammatory agent with proven synovial prostaglandin inhibitory effect.2 Measurements of prostaglandin E(2) (PGE(2)), thromboxane (TX) B(2), 6-keto-PGF(1alpha) and PGF(2alpha) were performed by radioimmunoassay techniques in synovial effusions obtained from 23 patients, and validated by thin-layer chromatographic analysis of the extracted immunoreactivity.3 PGE(2) and TXB(2) accounted for more than 60% of the total immunoreactivity in untreated patients. The absence of any constant ratio between the different arachidonic acid metabolites detected in synovial fluid is consistent with a heterogeneous cellular origin of these compounds.4 Indoprofen treatment was associated with a consistent reduction of synovial prostaglandin and thromboxane concentrations, ranging from 36% in the case of 6-keto-PGF(1alpha) to 90% in the case of PGE(2).5 In contrast, 6-MeP caused opposite changes on different metabolites originating via the cyclo-oxygenase pathway. Thus, 6-keto-PGF(1alpha) concentrations were reduced by 35%, PGF(2alpha) concentrations were increased by 30%, while PGE(2) and TXB(2) were unchanged following 6-MeP.6 Although the mechanism(s) underlying the failure of 6-MeP to reduce synovial PGE(2) and TXB(2) levels are uncertain, the results of the present study clearly indicate that therapeutic doses of steroidal and nonsteroidal anti-inflammatory drugs cause quite distinct changes in arachidonic acid metabolism, which might be relevant to their specific therapeutic actions and side-effects.


Thoracic outlet syndrome with congenital pseudarthrosis of the clavicle: treatment by brachial plexus decompression, plate fixation and bone grafting.
Although a number of cases of congenital pseudarthrosis of the clavicle have been described in the literature, they provide little direction for the treatment of this condition when it is associated with thoracic outlet syndrome. The authors describe their experience with such a case in a 20-year-old woman. Symptoms of pain in the ulnar distribution of the right forearm and discoloration of the hand with abduction of the extremity had developed over 3 years. The radial pulse was obliterated by abduction of the arm. Exploration of the brachial plexus revealed a constricting band arising from the distal fragment of the clavicle running to the first rib which, together with the mass of the pseudarthrosis, comprised the thoracic outlet. The patient was successfully treated by division of the fibrous band, reduction of the clavicle, internal fixation with a plate and iliac crest bone grafting. At follow-up the patient had a full range of motion in the shoulder and was asymptomatic.


Effects of Purple Corn Anthocyanin on Growth Performance, Meat Quality, Muscle Antioxidant Status, and Fatty Acid Profiles in Goats.
This study was conducted to examine the effect of purple corn anthocyanin on performance, meat quality, muscle antioxidant activity, antioxidant gene expression, and fatty acid profiles in goats. The feeding trial period lasted 74 d. The adaptation period was 14 d, and the formal experimental period was 60 d. Eighteen Qianbei-pockmarked goats (Guizhou native goat breed; body weight, 21.38 ± 1.61 kg; mean ± standard deviation) were randomly allotted into three equal groups, including a control with no purple corn pigment (PCP) and groups receiving either 0.5 g/d PCP or 1.0 g/d PCP. The inclusion of PCP did not affect (p > 0.05) the dry matter intake, average daily gain, or feed conversion ratio compared to the control group. The addition of PCP reduced (p < 0.05) shear force in the longissimus thoracis et lumborum muscle (LTL) during the growth phase of the goats. Goats receiving PCP showed higher (p < 0.05) levels of reduced glutathione, 2,2-diphenyl-1-picrylhydrazyl scavenging activity and peroxidase in LTL compared to the control. Moreover, compared to the control, the PCP group displayed lower (p < 0.05) concentrations of 12:0, C16:0, and total saturated fatty acids, but increased (p < 0.05) concentrations of various unsaturated fatty acids, including C18:1n9, C20:3n6, C20:4n6, C18:2n6 cis, C20:3n6, C22:5n3, C22:6n3, and total polyunsaturated fatty acids (PUFAs). The abundance of nuclear factor, erythroid 2 like 2, superoxide dismutase 1, glutathione peroxidase 1, and catalase was upregulated (p < 0.05) in the LTL of goats receiving 0.5 g/d PCP in comparison to the other groups. Collectively, result of the current study indicated that PCP anthocyanin could be used as a source of natural functional additive because anthocyanin-rich PCP has the potential to improve meat quality and enhance muscle antioxidant status as well as improve the proportions of PUFAs in goat muscle.


Evolutionary conservation and variation of protein folding pathways. Two protease inhibitor homologues from black mamba venom.
The pathways of unfolding and refolding of three homologous proteins are shown to be closely related. This implies that folding pathways, as well as the final folded conformation, have been largely conserved during the presumed evolutionary divergence of these proteins from a common ancestor. The pathways of the homologous proteins I and K from black mamba venom were determined here, using the disulphide interaction between their six cysteine residues to trap and identify the intermediate states, and are compared with those determined previously in the same way for the homologous bovine pancreatic trypsin inhibitor. The major one- and two-disulphide intermediates are the same with all three proteins; their kinetic roles are similar, although there are differences in the rates at which they are interconverted and in the minor intermediates that accumulate. As a consequence, different pathways may predominate with another homologous protein, even though the various most favourable pathways are the same. The energetics of the folding transitions and the stabilities of the folded states differ substantially for the three proteins. The differences in stabilities of the fully folded states are primarily reflected kinetically in the rate-determining rearrangements of the native-like conformation; the rates and equilibria of the other steps are not affected markedly. With the less stable proteins, the direct folding pathway of sequential formation of the three correct disulphide bonds becomes significant and is the most facile when considered on a solely intramolecular basis.


MoDUO1, a Duo1-like gene, is required for full virulence of the rice blast fungus Magnaporthe oryzae.
Duo1, a major component of the Dam1 complex which has been found in two species of yeast (the budding yeast Saccharomyces cerevisae and the fission yeast Schizosaccharomyces pombe), is involved in mitosis-related chromosome segregation, while its relevance to pathogenicity in filamentous fungi remains unclear. This report elucidated this very fact in the case of the rice blast fungus Magnaporthe oryzae. A gene designated MoDUO1 that encodes a Duo1-like homolog (MoDuo1) was discovered in the M. oryzae genome. Two types of MoDUO1 mutants were obtained using genetic approaches of Agrobacterium-mediated gene disruption and homologous recombination. Both disruption and deletion of MoDUO1 can exert profound effects on the formation pattern of conidiophores and conidial morphology, such as abnormal nucleic numbers in conidia and delayed extension of infectious hyphae. Intriguingly, plant infection assays demonstrated that inactivation of MoDUO1 significantly attenuates the virulence in its natural host rice leaves, and functional complementation can restore it. Subcellular localization assays showed that MoDuo1 is mainly distributed in the cytosol of fungal cells. Proteomics-based investigation revealed that the expression of four mitosis-related proteins is shut down in the MoDUO1 mutant, suggesting that MoDuo1 may have a function in mitosis. In light of the fact that Duo1 orthologs are widespread in plant and human fungal pathogens, our finding may represent a common mechanism underlying fungal virulence. To the best of our knowledge, this is the first example of linking a Duo1-like homolog to the pathogenesis of a pathogenic fungus, which might provide clues to additional studies on the role of Dam1 complex in M. oryzae and its interaction with rice.


Antigen presentation by brain microvessel smooth muscle and endothelium.
It has been previously reported that cultured brain microvessel smooth muscle cells (SM) express major histocompatibility complex (MHC) class II antigen. Here we report that SM is able to present ovalbumin (OVA) antigen to an OVA-specific T cell hybridoma (A2.2E10) and also presents keyhole limpet hemocyanin (KLH) to a KLH-specific T cell clone (HDK-1). Both the class II expression and the antigen-presenting capacity of SM cells is increased by interferon-gamma stimulation. Antigen presentation by SM is also MHC restricted as it is blocked by anti-Ia monoclonal antibodies. In contrast to SM, brain endothelium (En) presents whole OVA, digested OVA and KLH poorly, to a much lesser degree than SM, to the same antigen-specific T cells.


Hemodynamic and catecholamine responses during tracheal intubation using a lightwand device (Trachlight) in elderly patients with hypertension.
Tracheal intubation using a lightwand device (Trachlight) should minimize hemodynamic change by avoiding direct-vision laryngoscopy. We evaluated hemodynamic and catecholamine responses during tracheal intubation using a Trachlight in elderly patients with hypertension. Twenty-six hypertensive patients aged over 65 years undergoing orthopedic surgery were randomly divided into two groups, group L (n = 13) and group T (n = 13). Anesthesia was induced with fentanyl (2 microg x kg(-1)) and propofol (1.5 mg x kg(-1)), and then muscle relaxation was obtained with vecuronium (0.15 mg x kg(-1)). The trachea was intubated with either a Macintosh laryngoscope (group L) or a Trachlight (group T). Hemodynamics, plasma catecholamine concentrations, and arterial blood gases were measured before the induction of anesthesia (T0), before tracheal intubation (T1), immediately after tracheal intubation (T2), and 3 min after tracheal intubation (T3). The intubation time was shorter in group T than in group L (12.6 +/- 1.7 vs 23.5 +/- 2.9 s, mean +/- SE; P < 0.01). Compared with the preinduction (T0) value, systolic blood pressure (SBP) showed a significant decrease at T1 and T3 in group L and at T1, T2, and T3 in group T. The heart rate (HR) and plasma norepinephrine (NE) concentration showed no change in either group throughout the time course, whereas the plasma epinephrine (E) concentration showed a significant decrease at T2 and T3 in both groups. The mean values of the rate-pressure product (RPP: HR x SBP) were less than 15000 after tracheal intubation in both groups. There was no significant difference in hemodynamic or catecholamine responses between groups at any point. No patient had ischemic ST-T changes in either group. A lightwand has no advantage over a laryngoscope in terms of hemodynamic and plasma catecholamine responses to tracheal intubation in elderly patients with hypertension, despite a shorter intubation time.


Initiation-promotion skin carcinogenesis: inhibition by cyclic and non-cyclic nucleotides.
The effect of nucleotides on initiation-promotion skin carcinogenesis in Swiss mice was investigated. Cyclic AMP was given before initiation with DMBA, between initiation and promotion, and at the same time as promotion with croton oil. Cyclic AMP was more effective in inhibiting tumor development when injected at the same as promotion with croton oil. 5'-adenosine-monophosphate (5'-AMP) and cyclic GMP were as effective as cyclic AMP in inhibiting tumor development under these conditions. However, adenosine, dibutyryl-cyclic AMP and 5'-guanosine-monophosphate (5'-GMP) were ineffective.


Compilation of Modern Technologies To Map Genome-Wide Cytosine Modifications in DNA.
Over the past few decades, various DNA modification detection methods have been developed; many of the high-resolution methods are based on bisulfite treatment, which leads to DNA degradation, to a degree. Thus, novel bisulfite-free approaches have been developed in recent years and shown to be useful for epigenome analysis in otherwise difficult-to-handle, but important, DNA samples, such as hmC-seal and hmC-CATCH. Herein, an overview of advances in the development of epigenome sequencing methods for these important DNA modifications is provided.


Proteomic identification of malignant transformation-related proteins in esophageal squamous cell carcinoma.
Esophageal cancer (EC) persists to be a leading cancer-related death in northern China. Clinical outcome of EC is the most dismal among many types of digestive tumors because EC at early stage is asymptomatic. The current study used 2-DE-based proteomics to identify differentially expressed proteins between esophageal cancer cell lines and immortal cell line. Fifteen proteins were identified with differences of more than five folds, comprising the down-regulation of annexin A2, histone deacetylase 10 isoform beta and protein disulfide-isomerase ER-60 precursor, and the up-regulation of heat shock 70 kDa protein 9B precursor, solute carrier family 44 Member 3, heterogeneous nuclear ribonucleoprotein L (hnRNP L), eukaryotic translation initiation factor 4A isoform 2, triosephosphate isomerase1 (TPI), peroxiredoxin1 (PRX1), forminotransferase cyclodeaminase form (FTCD), fibrinogen gamma-A chain precursor, kinesin-like DNA binding protein, lamin A/C, cyclophilin A (CypA), and transcription factor MTSG1. Expression pattern of annexin A2 was verified by Western blotting, immunocytochemistry and immunohistochemistry analysis. The implication of these protein alterations correlated to the esophageal malignant transformation is discussed.


The contribution of gender-role orientation, work factors and home stressors to psychological well-being and sickness absence in male- and female-dominated occupational groups.
The associations of work stress, types of work and gender-role orientation with psychological well-being and sickness absence were investigated in a questionnaire survey of 588 male and female nurses and 387 male and female accountants. We hypothesised that health might be impaired among women working in the male-dominated occupation (accountancy), and men in the female-dominated occupation (nursing), but that effects might be moderated by job strain (perceptions of high demand and low control), work and home hassles, and traditional male (instrumentality) and female (expressivity) psychological characteristics. Responses were analysed from 172 female and 61 male nurses, and from 53 female and 81 male commercial accountants. Female accountants were more likely than other groups to have high anxiety scores on the Hospital Anxiety and Depression Scales, while male nurses had the highest rates of sickness absence. Male nurses and female accountants also reported more work-related hassles than did female nurses and male accountants. Men and women in the same occupation did not differ in job strain or job social support, but nurses reported greater job strain than accountants, due to higher ratings of demands and lower skill utilisation. After adjusting for age, sex, occupation, paid work hours and a measure of social desirability bias, risk of elevated anxiety was independently associated with higher job strain, lower job social support, more work hassles, more domestic responsibility, lower instrumentality and higher expressivity. The association between sex and anxiety was no longer significant after instrumentality had been entered into the regression model. Sickness absence of more than three days over the past 12 months was independently associated with higher job strain, more work hassles, lower instrumentality and higher expressivity. The results suggest that when men and women occupy jobs in which they are in the cultural and numerical minority, there may be adverse health effects that are gender-specific. Psychological traits related to socially constructed gender roles may also be relevant, and mediate in part the differences in psychological well-being between men and women.


MABTRAINS: Numerous anti-infective modalities ride together.
In this issue of Cell Host & Microbe, Buckley et al. report a biological entity called a mAbtyrin, which combines various antimicrobial functions. The authors demonstrate through in vitro and in vivo experiments that this approach can lead to highly effective antimicrobial action against Staphylococcus aureus.


Localized septal hypertrophy: part of the spectrum of hypertrophic cardiomyopathy or an incidental echocardiographic finding?
In a prospective study of the results of 5582 consecutive two-dimensional echocardiographic examinations, hypertrophy of a localized region of the basal ventricular septum was identified in 26 patients. Proven diagnoses were coronary disease in five patients, coronary plus valvular disease in three, valvular disease in seven, and miscellaneous in four. Localized septal hypertrophy was the only cardiac diagnosis in seven patients. The ratio of the thickness of the hypertrophied area to that of the adjacent septum was greater than or equal to 1.7 (mean 1.93 +/- 0.19) in all patients. The ration of the length of the hypertrophied portion (mean 0.34 +/- 06) to the length (apex to base) of the septum was less than 0.39 in all but one patient. Although the mitral valve tended to be more anterior than expected in 20, other features of hypertrophic cardiomyopathy were generally lacking. Of four patients undergoing left ventricular angiography, the bulge was identified in only one in whom cranial-caudal angulation was added to the 60-degree left anterior oblique view. An autopsy was performed in one patient; the hypertrophy was identified, although results of microscopic examination showed no fiber disarray. These data suggest that, in most instances, localized septal hypertrophy is an incidental echocardiographic finding. The diagnosis of hypertrophic cardiomyopathy should generally not be made on the basis of this feature alone.


Solid lipid nanoparticles (SLN) of Efavirenz as lymph targeting drug delivery system: Elucidation of mechanism of uptake using chylomicron flow blocking approach.
The aim of the present work was to develop a lymph targeted SLN formulation of antiretroviral (ARV) drug and to have an understanding of its underlying mechanism of uptake by the lymphatics. The lymphatics are the inaccessible reservoirs of HIV in human body. Efavirenz (EFV) is a BCS class II, ARV drug that undergoes extensive first pass metabolism. The EFV SLN formulation was prepared using Gelucire 44/14, Compritol 888 ATO, Lipoid S 75 and Poloxamer 188 by hot homogenization technique followed by ultrasonication method, with mean particle size of 168 nm, polydispersity index (PDI) <0.220, and mean zeta potential of -35.55 mV. DSC and XRPD studies revealed change in crystallinity index of drug when incorporated into SLN. In vitro drug release was found to be prolonged and biphasic in PBS pH 6.8. There was no significant change in the mean particle size, PDI, zeta potential and entrapment efficiency of EFV SLN after storage at 30 ± 2°C/60 ± 5%RH for two months. The results from lymphatic transport and tissue distribution study indicate that a significant part of the EFV had by-passed portal system and was recovered in the lymph via chylomicron uptake mechanism. Reduction in the amount (44.70%) of the EFV reaching to liver indicates that major amount of EFV bypasses the liver and thereby, enhances the oral bioavailability of the EFV. A significant amount of EFV was found in spleen, a major lymphatic organ. EFV SLN seems to have potential to target the ARV to lymphatics for the better management of HIV.


Alterations in peripheral joint muscle force control in adults with musculoskeletal disease, injury, surgery, or arthroplasty: A systematic review and meta-analysis.
To systematically review and analyse whether musculoskeletal conditions affect peripheral joint muscle force control (i.e. magnitude and/or complexity of force fluctuations). A literature search was conducted using MEDLINE, CINAHL and SPORTDiscus databases (from inception-8th April 2021) for studies involving: 1) participants with musculoskeletal disease, injury, surgery, or arthroplasty in the peripheral joints of the upper/lower limb; 2) comparison with an unaffected control group or unaffected contralateral limb; and 3) measures of the magnitude and/or complexity of force fluctuations during targeted isometric contractions. The methodological quality of studies was evaluated using a modified Downs and Black Quality Index. Studies were combined using the standardized mean difference (SMD) in a random-effects model. 14 studies (investigating 694 participants) were included in the meta-analysis. There was a significant effect of musculoskeletal conditions on peripheral joint muscle force coefficient of variation (CV; SMD = 0.19 [95 % CI 0.06, 0.32]), whereby individuals with musculoskeletal conditions exhibited greater CV than controls. Subgroup analyses revealed that CV was only greater: 1) when comparison was made between symptomatic and asymptomatic individuals (rather than between affected and contralateral limbs; SMD = 0.22 [95 % CI 0.07, 0.38]); 2) for conditions of the knee (SMD = 0.29 [95 % CI 0.14, 0.44]); and 3) for ACL injury post-surgery (SMD = 0.56 [95 % CI 0.36, 0.75]). Musculoskeletal conditions result in an increase in peripheral joint muscle force CV, with this effect dependent on study design, peripheral joint, and surgical status. The greater force CV is indicative of decreased force steadiness and could have implications for long-term tissue health/day-to-day function.


Swallowing disorders in Parkinson's disease.
Parkinson's disease is a type of chronic neurodegenerative pathology with a typical movement pattern, as well as different, less studied symptoms such as dysphagia. Disease-related disorders in efficacy or safety in the process of swallowing usually lead to malnutrition, dehydration or pneumonias. The aim of this study was identifying and analyzing swallowing disorders in Parkinson's disease. The initial sample consisted of 52 subjects with Parkinson's disease to whom the specific test for dysphagia SDQ was applied. Nineteen participants (36.5%) with some degree of dysphagia in the SDQ test were selected to be evaluated by volume-viscosity clinical exploration method and fiberoptic endoscopic evaluation of swallowing. Disorders in swallowing efficiency and safety were detected in 94.7% of the selected sample. With regards to efficiency, disorders were found in food transport (89.5%), insufficient labial closing (68.4%) and oral residues (47.4%), relating to duration of ingestion. Alterations in security were also observed: pharynx residues (52.7%), coughing (47.4%), penetration (31.64%), aspiration and decrease of SaO2 (5.3%), relating to the diagnosis of respiratory pathology in the previous year. The SDQ test detected swallowing disorders in 36.5% of the subjects with Parkinson's disease. Disorders in swallowing efficiency and safety were demonstrated in 94.7% of this subset. Disorders of efficiency were more frequent than those of safety, establishing a relationship with greater time in ingestion and the appearance of respiratory pathology and pneumonias.


Treatment of patent ductus arteriosus.
Patent ductus arteriosus (PDA) continues to be one of the most common problems found in premature infants. The incidence is inversely related to gestation, but may be reduced by use of antenatal steroids, lower volume fluid regimen and judicious use of phototherapy. However, there continues to be controversy as to the appropriate indications for treatment, varying from prophylaxis on the basis of gestation to treatment only when a PDA is demonstrably significant. The situation is further complicated by differing diagnostic criteria for ductal patency or significance. Prophylactic treatment is likely to result in up to 64% of babies being treated unnecessarily. Early treatment of significant or symptomatic PDA depends upon accurate diagnosis. PDA closure can then be achieved using medical means, with surgery reserved for patients in whom this fails or in whom there are contra-indications. However, the optimum timing for intervention remains unknown.


Comparison of transcatheter leaflet-approximation and direct annuloplasty in tricuspid regurgitation.
Transcatheter repair emerges as a treatment option in patients with tricuspid regurgitation (TR) and high surgical risk. This study aimed to compare leaflet-based and annuloplasty-based transcatheter repair in patients with TR. In a retrospective analysis consecutive patients undergoing either transcatheter edge-to-edge repair (TEER) or direct annuloplasty (AP) for relevant TR at 2 centers were compared with respect to baseline characteristics, procedural efficacy and safety (death, myocardial infarction, procedure or device-related cardiothoracic surgery, or stroke at 30 days). 161 patients (57% female, median age 79 [75-82] years) with comparable clinical baseline characteristics in the TEER (n = 87) and AP (n = 74) group were examined. Baseline TR grade was significantly less severe in the TEER compared to the AP group (torrential 9.2 vs. 31.1%, p = 0.001). Technical success and improvement of TR grades were not significantly different across groups. In analysis matched for baseline TR severity, reduction of TR grade to less than moderate was significantly more common in the AP group (47.8 vs. 26.1%, p = 0.031). Major or more severe bleeding occurred in 9.2% of TEER and 20.3% of AP patients (p = 0.049) without any fatal bleedings. Major adverse events (MAE) were similar across groups with four patients (4.7%) in the TEER group and five patients (6.9%) in the AP group (p = 0.733) and 6-month survival did not differ significantly. Differences observed between patients treated with TEER and AP provide first evidence for tailoring distinct transcatheter treatment techniques to individual patient characteristics.


Ion exchanger in the brain: Quantitative analysis of perineuronally fixed anionic binding sites suggests diffusion barriers with ion sorting properties.
Perineuronal nets (PNs) are a specialized form of brain extracellular matrix, consisting of negatively charged glycosaminoglycans, glycoproteins and proteoglycans in the direct microenvironment of neurons. Still, locally immobilized charges in the tissue have not been accessible so far to direct observations and quantifications. Here, we present a new approach to visualize and quantify fixed charge-densities on brain slices using a focused proton-beam microprobe in combination with ionic metallic probes. For the first time, we can provide quantitative data on the distribution and net amount of pericellularly fixed charge-densities, which, determined at 0.4-0.5 M, is much higher than previously assumed. PNs, thus, represent an immobilized ion exchanger with ion sorting properties high enough to partition mobile ions in accord with Donnan-equilibrium. We propose that fixed charge-densities in the brain are involved in regulating ion mobility, the volume fraction of extracellular space and the viscosity of matrix components.


[Biomechanical investigations of the ankle joint after shortening of the distal end of the fibula (author's transl)].
Shortening of the distal fibula after malleolar fracture is accompanied with important alterations of the biomechanics and the compressive forces of the ankle joint. The relationship between the extent of shortening, the degree of valgus position of the talus and the reduction of the joint surfaces is described on the basis of experimental investigations. The importance of these circumstances for treatment of malleolar fractures is discussed.


Individual- and Environmental- Level Predictors of Recess Activity and Sedentary Behavior: Findings from the I-CAN! study.
Recess represents a prime opportunity for physical activity during the school day. However, evidence is mixed with regard to factors associated with activity during recess. Data were collected as a part of the Texas Initiative for Children's Activity and Nutrition (I-CAN!) program from 14 elementary schools and 1,049 4th-grade students. Percent of time in moderate-to-vigorous physical activity (MVPA) and sedentary behavior during recess was measured using GT3X+ accelerometers. Students' demographics, aerobic fitness, and body mass index (BMI) were collected from school records and FITNESSGRAM® data. Aspects of the playground environment supporting activity (e.g. soccer goals) or sedentary behavior (e.g. benches) were calculated following the procedures of the System for Observing Play and Leisure Activity in Youth (SOPLAY), with recess spatial area calculated via the polygon measurement tool in Google™ Earth Pro software. Recess time was collected from school data. Weather during recess was determined using time-stamped archived weather data from Weather Underground. Two-level, linear mixed model regression examined associations between individual- and school-level characteristics and percent time in MVPA. At the student-level, boys were more active than girls (effect size (ES)=0.50) and percent time in MVPA was directly associated with aerobic fitness (ES=0.35). At the school-level, recess infrastructure was associated with percent time in MVPA (ES=1.45), except for factors related to sedentary behavior, which were indirectly associated with percent time in MVPA (ES=-1.98). Patterns for sedentary behavior mirrored these effects. This is one of the few studies to test the associations of fitness and sedentary upgrades to play areas with MVPA and sedentary behavior. The results suggest that recess is most likely to support MVPA in boys and those who are already most fit (i.e., those who would not be the target of intervention). This is not surprising because the focus of recess is on free choice of play, and thus recess might be supported more for social and emotional benefits than the impact on physical activity.


Numerical study on the adhesion of a circulating tumor cell in a curved microvessel.
The adhesion of a circulating tumor cell (CTC) in a three-dimensional curved microvessel was numerically investigated. Simulations were first performed to characterize the differences in the dynamics and adhesion of a CTC in the straight and curved vessels. After that, a parametric study was performed to investigate the effects of the applied driven force density f (or the flow Reynolds number Re) and the CTC membrane bending modulus Kb on the CTC adhesion. Our simulation results show that the CTC prefers to adhere to the curved vessel as more bonds are formed around the transition region of the curved part due to the increased cell-wall contact by the centrifugal force. The parametric study also indicates that when the flow driven force f (or Re) increases or when the CTC becomes softer (Kb decreases), the bond formation probability increases and the bonds will be formed at more sites of a curved vessel. The increased f (or Re) brings a larger centrifugal force, while the decreased Kb generates more contact areas at the cell-wall interface, both of which are beneficial to the bond formation. In the curved vessel, it is found that the site where bonds are formed the most (hotspot) varies with the applied f and the Kb. For our vessel geometry, when f is small, the hotspot tends to be within the first bend of the vessel, while as f increases or Kb decreases, the hotspot may shift to the second bend of the vessel.


Bilateral symptomatic large cavernous carotid artery aneurysms treated by extracranial-intracranial bypass with parent artery occlusion.
Bilateral large cavernous sinus internal carotid aneurysms (CCAs) occur very rarely. While the choice of treatment method is important, the timing of contralateral side treatment is equally important. We herein report the case of a 72-year-old woman who presented with progressive bilateral visual impairment and was treated by two-stage. First, the left CCAs had been treated, and the aneurysm was thrombosed, but her left visual acuity did not recover; the right CCA was becoming larger 2 years later, and her right visual acuity began worsening. The right CCAs was treated by almost same method. Her right visual acuity improved compared with the second preoperative findings. Our case findings suggest the importance of considering the appropriate timing to avoid symptom aggravation in patients with bilateral CCAs.


Effects of the daily consumption of protein enriched bread and protein enriched drinking yoghurt on the total protein intake in older adults in a rehabilitation centre: a single blind randomised controlled trial.
To investigate the effects of protein enriched bread and drinking yoghurt, substituting regular products, on the total protein intake and the distribution of protein intake over the day in older adults. A single blind randomised controlled trial. Rehabilitation centre. Older adults (≥ 55 years) admitted to a rehabilitation centre after hospital discharge (n=34). Participants received a high protein diet (protein enriched bread and protein enriched drinking yoghurt; n=17) or a regular diet (regular bread and regular drinking yoghurt; n=17) for three consecutive weeks. Total protein intake and protein intake per meal, measured twice weekly over a three weeks period (six measurements per participant). Compared with controls, patients who received the protein enriched products had a significantly higher protein intake (115.3 g/d vs 72.5 g/d, P<0.001; 1.6 g/kg/d vs 1.1 g/kg/d, P<0.001). The intervention group consumed quantities over the recommended level (25-30 g/meal) during each of the three meals (32.5 g, 30.0 g, 34.8 g/meal), where the control group consumed quantities below the recommended level during breakfast (17.7 g) and lunch (18.4 g). The use of protein enriched products, replacing regular products, results in a significant increased daily protein intake in older adults. In addition, the daily consumption of protein enriched products improves protein distribution over the day.


The usefulness of subtraction ictal SPECT coregistered to MRI in single- and dual-headed SPECT cameras in partial epilepsy.
To prove the clinical usefulness of SISCOM and compare SISCOM images derived from single- and dual-headed single-photon computed tomography (SPECT) cameras for localization of partial epileptic seizures. We retrospectively studied 38 partial epilepsy patients, using subtraction SPECT coregistered to magnetic resonance imaging (MRI; SISCOM). SPECT imaging of the first 15 patients was performed by single-headed camera, and the next 23 patients by dual-headed camera. Side-by-side ictal-interictal SPECT evaluation and SISCOM images were blindly reviewed and classified as either localizing to one of 16 sites or nonlocalizing. A third reviewer evaluated cases of disagreement between primary reviewers. Results were compared with seizure localization by any of the following three traditional techniques: surgical outcome, invasive, and noninvasive video-EEG monitoring. The results from the single- and dual-headed SPECT cameras were compared. Reviewers localized areas of hyperperfusion with SISCOM images more often than with side-by-side SPECT evaluation (71.0 vs. 47.4%; p = 0.01). When we compared results of SPECT evaluation with traditional techniques, SISCOM showed greater concordance than side-by-side SPECT evaluation (60.53 vs. 36.84%; p = 0.006). There were no differences in localization between images derived from single- and dual-headed cameras. Concordance of seizure localization, compared with traditional techniques, also was not different between these groups [kappa = 0.38, 95% confidence interval (CI), 0.18-0.58] vs. kappa = 0.63, 95% CI (0.45-0.81)]. SISCOM is a worthwhile technique for preoperative evaluation in partial epilepsy patients and improves the sensitivity and specificity of seizure localization of SPECT images derived from both single- and dual-headed SPECT cameras.


Performance and mechanism of a novel S-scheme heterojunction sonocatalyst CuS/BaWO4 for degradation of bisphenol A by ultrasonic activation.
A novel CuS/BaWO4 heterojunction catalyst was prepared and characterized. Taking bisphenol A as the target pollutant for catalytic degradation, the sonocatalytic activity of CuS/BaWO4 composite was evaluated, and the combination with persulfate improved the sonocatalytic degradation of bisphenol A. The results showed that CuS/BaWO4 composite had good sonocatalytic degradation activity for bisphenol A, and the degradation rate was 70.99% ± 1.46%. After combined with persulfate, the degradation rate was further increased to 95.34% ± 0.10%, and the reaction time was relatively shortened. The results of the trapping experiment and calculated energy band positions showed that the formation of S-scheme heterojunction and the formation of hydroxyl radicals and holes were the key to the catalytic degradation of bisphenol A by CuS/BaWO4 composite. In this study, a new CuS/BaWO4 heterojunction sonocatalyst was synthesized. The catalyst can efficiently remove bisphenol A from the water environment and can be used as a potential solution for endocrine disruptor pollution in the water environment.


Reactive landing of peptide ions on self-assembled monolayer surfaces: an alternative approach for covalent immobilization of peptides on surfaces.
Soft landing of mass-selected peptide ions onto reactive self-assembled monolayer surfaces (SAMs) was performed using a newly constructed ion deposition apparatus. SAM surfaces before and after soft landing were characterized ex situ using time-of-flight secondary-ion mass spectrometry (TOF-SIMS) and infrared reflection-absorption spectroscopy (IRRAS). We demonstrate that reactive landing (RL) results in efficient covalent linking of lysine-containing peptides onto the SAM of N-hydroxysuccinimidyl ester-terminated alkylthiol on gold (NHS-SAM). Systematic studies of the factors that affect the efficiency of RL revealed that the reaction takes place upon collision and is promoted by the kinetic energy of the ion. The efficiency of RL is maximized at ca. 40 eV collision energy. At high collision energies the RL efficiency decreases because of the competition with scattering of ions off the surface. The reaction yield is independent of the charge state of the projectile ions, suggesting that peptide ions undergo efficient neutralization upon collision. Chemical and physical properties of the SAM surface are also important factors that affect the outcome of RL. The presence of chemically reactive functional groups on the SAM surface significantly improves the reaction efficiency. RL of mass- and energy-selected peptide ions on surfaces provides a highly specific approach for covalent immobilization of biological molecules onto SAM surfaces.


The in vitro fertilization of supernumerary oocytes in a gamete intrafallopian transfer program.
Gamete intrafallopian transfer (GIFT) was performed on a series of 42 couples in whom four oocytes were replaced into the fallopian tubes and the remaining oocytes were inseminated with 100,000 motile spermatozoa. Fertilization in vitro was assessed 16 to 20 hours later. An overall pregnancy rate after GIFT of 40.0% (12/30) in normospermic couples and 16.7% (2/12) in oligospermic couples was seen. Supernumerary oocytes were submitted to in vitro fertilization (IVF) and the findings related to the likelihood of pregnancy. No correlation between IVF and the likelihood of GIFT pregnancies was found in either the oligospermic or normospermic couples. A similar proportion of pregnancies was seen in couples with or without evidence of fertilization of the supernumerary oocytes in both the oligospermic and normospermic couples. However, a high proportion of normospermic couples with no evidence of fertilization had only one oocyte remaining for insemination. These results suggest that the failure of low numbers of supernumerary oocytes to fertilize in vitro after GIFT relates to oocyte selection criteria and does not mean a reduced chance of conception in that treatment cycle.


Clinical evaluation of rare copy number variations identified by chromosomal microarray in a Hungarian neurodevelopmental disorder patient cohort.
Neurodevelopmental disorders are genetically heterogeneous pediatric conditions. The first tier diagnostic method for uncovering copy number variations (CNVs), one of the most common genetic etiologies in affected individuals, is chromosomal microarray (CMA). However, this methodology is not yet a routine molecular cytogenetic test in many parts of the world, including Hungary. Here we report clinical and genetic data of the first, relatively large Hungarian cohort of patients whose genetic testing included CMA. Clinical data were retrospectively collected for 78 children who were analyzed using various CMA platforms. Phenotypes of patients with disease-causing variants were compared to patients with negative results using the chi squared/Fisher exact tests. A total of 30 pathogenic CNVs were identified in 29 patients (37.2%). Postnatal growth delay (p = 0.05564), pectus excavatum (p = 0.07484), brain imaging abnormalities (p = 0.07848), global developmental delay (p = 0.08070) and macrocephaly (p = 0.08919) were more likely to be associated with disease-causing CNVs. Our results allow phenotypic expansion of 14q11.2 microdeletions encompassing SUPT16H and CHD8 genes. Variants of unknown significance (n = 24) were found in 17 patients. We provide detailed phenotypic and genetic data of these individuals to facilitate future classification efforts, and spotlight two patients with potentially pathogenic alterations. Our results contribute to unraveling the diagnostic value of rare CNVs.


Lepidopteran defence droplets - a composite physical and chemical weapon against potential predators.
Insects often release noxious substances for their defence. Larvae of Zygaena filipendulae (Lepidoptera) secrete viscous and cyanogenic glucoside-containing droplets, whose effectiveness was associated with their physical and chemical properties. The droplets glued mandibles and legs of potential predators together and immobilised them. Droplets were characterised by a matrix of an aqueous solution of glycine-rich peptides (H-WG11-NH2) with significant amounts of proteins and glucose. Among the proteins, defensive proteins such as protease inhibitors, proteases and oxidases were abundant. The neurotoxin β-cyanoalanine was also found in the droplets. Despite the presence of cyanogenic glucosides, which release toxic hydrogen cyanide after hydrolysis by a specific β-glucosidase, the only β-glucosidase identified in the droplets (ZfBGD1) was inactive against cyanogenic glucosides. Accordingly, droplets did not release hydrogen cyanide, unless they were mixed with specific β-glucosidases present in the Zygaena haemolymph. Droplets secreted onto the cuticle hardened and formed sharp crystalline-like precipitates that may act as mandible abrasives to chewing predators. Hardening followed water evaporation and formation of antiparallel β-sheets of the peptide oligomers. Consequently, after mild irritation, Zygaena larvae deter predators by viscous and hardening droplets that contain defence proteins and β-cyanoalanine. After severe injury, droplets may mix with exuding haemolymph to release hydrogen cyanide.


Gait analysis of leprosy patients with foot drop using principal component analysis.
Peripheral nerve injury caused by leprosy can lead to foot drop, resulting in an altered gait pattern that has not been previously described using 3D gait analysis. Gait kinematics and dynamics were analyzed in 12 patients with unilateral foot drop caused by leprosy and in 15 healthy controls. Biomechanical data from patients' affected and unaffected limbs were compared with controls using inferential statistics and a standard distance, based on principal components analysis (PCA). Patients walked slower than controls (0.8 ± 0.2 vs. 1.1 ± 0.2 m/s, p = 0.003), with a reduced stance and increased swing percentage. The affected limb increased (p < 0.05) plantar flexion at the initial contact (-16.8o ± 8.3), terminal stance (-29.1o ± 11.5), and swing (-12.4o ± 6.2) in the affected limb compared to unaffected (-6.6o ± 10.3; -14.6o ± 11.6; 2.4o ± 7.6) and controls (-5.4o ± 2.5; -18.8o ± 5.8; -1.4o ± 3.9). Increased pelvic tilt and knee adduction/abduction range, with lower hip adduction, were observed. The second peak of ground reaction force (98.6 ± 5.2 %BW), ankle torque (0.99 ± 0.33 Nm/kg), and net ankle work in stance (-0.03 ± 5.4 J/Kg) decreased in the affected limb compared to controls (104.1 ± 5.5 %BW; 1.24 ± 0.4 Nm/kg; -4.58 ± 5.19 J/kg; p < 0.05). There were decreasing multivariate standard distances in the affected limb compared with the unaffected and controls. PCA loading factors highlighted the major differences between groups. Leprosy patients with foot drop presented altered gait patterns in affected and unaffected limbs. There were remarkable differences in ankle kinematics and dynamics. Rehabilitation devices, such as ankle foot orthosis or tendon transfer surgeries to increase ankle dorsiflexion, could benefit these patients and reduce deviations from normal gait.


Mediation and mechanisms of the hypotensive effect of L-dopa in the sea-gull: Larus argentatus.
We have investigated the mediation of the hypotensive action of L-DOPA after peripheral DOPA decarboxylase (DC) inhibition in the sea-gull, Larus argentatus. Vagotomy prevented the bradycardia and hypotension occurring after L-DOPA in birds pretreated with an inhibitor of peripheral DC. L-DOPA alone, given to intact birds, resulted in a slight increase in blood pressure (BP), accompanied by a tendency to bradycardia. Spinal transection in combination with vagotomy reversed the bradycardia and reinforced the increase in BP seen in intact birds after L-DOPA. The dopamine receptor antagonist spiroperidol did not alter the hypotension and bradycardia after L-DOPA in birds pretreated with a peripherally acting DC inhibitor. Yohimbine antagonized the effects of L-DOPA, restoring the BP to near basal values within 5 min after i.v. injections, while prazosin had no such effect. The heart rate returned towards basal values after both yohimbine and prazosin. We conclude that L-DOPA elicits its hypotensive action in the sea-gull via activation of central alpha-adrenoceptors, which may belong to the alpha 2-subtype. The bradycardia may involve central activation of adrenoceptors of both the alpha 1- and alpha 2-types. The hypotension and bradycardia are mediated via vagal activation and probably also inhibition of sympathetic nervous output. The functional significance of sympathetic fibres running along with the vagus nerve is suggested.


Interobserver variability, and visual and quantitative parameters of (123)I-FP-CIT SPECT (DaTSCAN) studies.
To evaluate the degree of interobserver agreement in the visual interpretation of (123)I-FP-CIT studies and to investigate for potential associations between visual and semi-quantitative parameters. Eighty-nine (123)I-FP-CIT studies were blindly reviewed by 3 independent observers: a consultant, a resident doctor and a radiographer. They classified every study as either "normal" or "abnormal" and assigned visual (123)I-FP-CIT uptake scores (2: normal, 1: reduced and 0: no uptake) in basal ganglia nuclei (right and left putamina and caudate nuclei) on every scan. Striatal (123)I-FP-CIT binding ratios were calculated using crescent-ROI software. The interobserver agreement for the interpretation of studies and for visual score assignment was evaluated by means of κ statistics. We investigated for associations of binding ratios with visual scores and clinical parameters; patients' clinical diagnoses served as the reference standard. There was excellent interobserver agreement (κ 0.89-0.93) in classifying studies as "normal" or "abnormal" and fine agreement in assignment of visual scores (κ 0.71-0.80 for putamina and 0.50-0.79 for caudate nuclei). Nuclei with scores of 1 and 0 showed significantly reduced binding ratios (about 30 and 50%, respectively) compared with the nuclei scored as 2. ROC analysis indicated the optimal cutoff point of striatal binding ratio at 3.8 (sensitivity 98.5%, specificity 95%) for the detection of parkinsonian syndromes. Striatal binding ratios were negatively associated with age in normal subjects and disease duration in Parkinson's disease patients. Visual interpretation of (123)I-FP-CIT studies showed very good interobserver agreement. We found significant associations among visual, semi-quantitative and clinical parameters.


β-Arrestin 1 (ARRB1) serves as a molecular marker of the peripheral circadian rhythm.
The control of the circadian rhythm is important for health because it regulates physiological functions and is associated with health hazards. We aimed to identify a circadian biomarker of health status in human saliva, since collecting saliva is non-invasive, straightforward, and cost-effective. Among 500 genes potentially controlled by the salivary clock identified using chromatin immunoprecipitation (ChIP) assays, 22 of them showed reasonable transcriptional responses according to a DNA array in a salivary model system. Among these 22 genes, ARRB1, which is expressed in human salivary glands, was also expressed in model HSG cells at the transcriptional and translational levels. The profile of ARRB1 expression in human saliva was circadian, suggesting that ARRB1 could serve as a candidate circadian biomarker in saliva. We compared ARRB1 with other biomarkers in salivary samples from jet-lagged individuals. The circadian profile of ARRB1 reflected the time lag more than the profile of melatonin, whereas the profiles of cortisol and α-amylase did not reflect the time lag. Overall, these findings suggest that salivary ARRB1 could serve as a candidate biomarker that could be used to monitor the internal body clock.