A comparison of primary dysmenorrhoea and intrauterine device related pain.
A pain questionnaire designed to measure sensory, affective, evaluative and temporal components of pain was administered to 119 patients with primary dysmenorrhoea and 75 patients with intrauterine device (IUD) related pain. In addition "self-report" information was obtained on the behavioural effects of pain, global ratings and biographical details of these patients. It was found that dysmenorrhoea and IUD related pain were generally similar in nature. This led to the conclusion that IUD insertion does not in general lead to an exacerbation of presenting dysmenorrhoea, nor does it radically alter the type of sensations experienced by the patient. While no differences between patient groups emerged, the implications of the different pain components did vary. Thus, pain intensity scores were reflected in a larger sensory component with IUD users, whereas with dysmenorrhoea the affective component predominated. The results show sufficient consensus in the two patient groups of word adjectives used to describe their pain, to allow the development and evaluation of a rapid card sort system for pain assessment.


Prelingual Deafness: An Overview of Treatment Outcome.
Prelingually deaf child is one who is either born deaf or who lost his or her hearing early in childhood, before acquiring language. A child with subnormal hearing acuity suffers from consequences of hearing loss compounded by impaired speech development. The period from birth to 3 years of life is critical for the development of speech and language, therefore, there is need for early identification and assessment of hearing loss and early rehabilitation in children. 40 patients were evaluated clinically, radiologically and audiologically to assess the degree of patient's handicap. The modes of treatment included use of hearing aid in patients with moderate, moderately-severe, severe or profound HL and cochlear implantation in patients with profound HL. Each patient was followed for 18 months and results were calculated in terms of speech perception (CAP) and language (REELS) development of the patient. Out of the 40 patients, 60% (n = 24) were females and 40% (16) were males. 50% (n = 20) patients had PSNHL, 32.5% (n = 13) had SSNHL, 10% (n = 4) had MSSNHL and 7.5% (n = 3) had MSNHL. 30% (n = 12) of patients had significant radiological findings. Among the hearing aid users patients with PSNHL got no benefit at the end of 18 months whereas the patients with cochlear implantation had significant improvement. Also the patients managed at a younger age (<3 years) had a significantly better outcome then those managed later. Early identification of hearing loss, that is followed by immediate and appropriate intervention results in better language, speech, and social-emotional development when compared to children treated at a later age.


Mitral annular calcium, inducible myocardial ischemia, and cardiovascular events in outpatients with coronary heart disease (from the Heart and Soul Study).
We sought to determine whether mitral annular calcium (MAC) is associated with inducible myocardial ischemia and adverse cardiovascular outcomes in ambulatory patients with coronary artery disease (CAD). MAC is associated with cardiovascular disease (CVD) in the general population, but its association with CVD outcomes in patients with CAD has not been evaluated. We examined the association of MAC with inducible ischemia and subsequent cardiovascular events in 1,020 ambulatory patients with CAD who were enrolled in the Heart and Soul Study. We used logistic regression to determine the association of MAC with inducible ischemia and Cox proportional hazards models to determine the association with CVD events (myocardial infarction, heart failure, stroke, transient ischemic attack or death). Models were adjusted for age, gender, race, smoking, history of heart failure, blood pressure, high-density lipoprotein, and estimated glomerular filtration rate. Of the 1,020 participants 192 (19%) had MAC. Participants with MAC were more likely than those without MAC to have inducible ischemia (adjusted odds ratio 2.06, 95% confidence interval 1.41 to 3.01, p = 0.0002). During an average of 6.26 ± 2.11 years of follow-up, there were 310 deaths, 161 hospitalizations for heart failure, 118 myocardial infarctions, and 55 cerebrovascular events. MAC was associated with an increased rate of cardiovascular events (adjusted hazard ratio 1.39, 95% confidence interval 1.08 to 1.79, p = 0.01). In conclusion, we found that MAC was associated with inducible ischemia and subsequent CVD events in ambulatory patients with CAD. MAC may indicate a high atherosclerotic burden and identify patients at increased risk for adverse cardiovascular outcomes.


Immunological and physicochemical characterization of heat-labile enterotoxins isolated from two strains of Escherichia coli.
Heat-labile enterotoxins from Escherichia coli strains of human and porcine origins had identical subunit composition, arrangement, and size in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunological differences recently described by others were shown to reside exclusively in the B subunits.


N- and C-terminal truncations of a GH10 xylanase significantly increase its activity and thermostability but decrease its SDS resistance.
XynII from Volvariella volvacea has high sodium dodecyl sulfate (SDS) resistance, with the potential for industrial applications under harsh conditions. It consists of a single glycoside hydrolase family 10 (GH10) catalytic domain but contains an additional unique 10 and 4 amino acid residues at the N- and C-terminus, respectively. In this study, five XynII derivatives with N- and/or C-terminus deletions were constructed to determine the effects of these regions on enzyme activity, substrate specificity, thermostability, and SDS resistance. Our results revealed that N- and/or C-terminal truncations significantly increased enzyme activity and thermostability, but reduced SDS resistance. Specifically, the XynIIΔNC4 mutant had 2.53-fold more catalytic efficiency (k cat/K m) towards beechwood xylan than wild-type and 3.0-fold more thermostability (t 1/2 [55°C]). XynIIΔNC4 displayed 3.33-, 4.38-, 1.37-, and 1.98-fold more activity against xylotriose, xylotetraose, xylopentaose, and xylohexaose, respectively, than XynII did. However, its half-life (t 1/2) in 4 % SDS was only 1.72 h, while that of XynII was 4.65 h. Circular dichroism analysis revealed that deletion of N- and C-terminal segments caused minor changes in secondary structure. Our observations suggest that the extra N- and C-terminal segments in wild-type XynII evolved to strengthen the interaction between these regions of the protein, making the local structure more rigid and reducing structural flexibility. In this way, N- and C-terminal truncations increased the thermostability and activity of XynII on different xylans and linear xylooligosaccharides, but reduced its resistance to SDS.


Osmotic properties of human lymphocyte.
The osmotic properties of human lymphocytes isolated from 15 ml of venous blood were examined. Measurements of the permeability of the membrane to water under an osmotic gradient were also made. The Boyle-Van't Hoff relation held very well for the human lymphocyte when the cells were shrunken in hyperosmotic media to concentrations twice isosmotic. The volume of osmotically inactive material or "b" value averaged 32% of the mean corpuscular volume. These values were independent of temperature. Ponder's R ranged between 0.8 and 0.9. The average value for Lp, the hydralic coefficient was 0.46 mu/min atm +/- 0.02 (S.E.M.) at 25 degrees C. No significant effect of age, sex, or race was noted. The effect of temperature between 10 degrees C and 37 degrees C was measured and heats of activation between 11.1 and 17.4 kcal/mole were calculated with a mean of 14.1 kcal/mole +/- 1.6 (S.E.M.). Concanavalin A at 10 microgram/1.5 X 10(6) lymphocytes produced blastogenesis of 25% or more of the lymphocytes without clumping, agglutination, or toxicity. The mean corpuscular volume increased by 21% after 72 hours due to an increase in the "b" value which increased by 80%. The volume of free water remained constant. Histograms of the distribution of cell volumes showed that volume changes were uniform throughout the population with no evidence of agglutination of clumping. The significance of these results is discussed in the context of membrane fluidity and the state of intracellular water.


Evaluation of the nodal status in the 7th edition of the UICC-TNM classification for esophageal squamous cell carcinoma: proposed modifications for improved survival stratification : impact of lymph node metastases on overall survival after esophagectomy.
The 7th edition of the Union for International Cancer Control-TNM (UICC-TNM) classification for esophageal carcinoma made considerable modifications to the definition of N-staging by the number of involved lymph nodes and the regional node boundary. There were few validations of the regional boundary. We evaluated the nodal status of this classification for esophageal squamous cell carcinoma (ESCC). There were 665 patients reviewed who had ESCC and underwent esophagectomy between 1997 and 2012. We evaluated the impact of the location of lymph node metastasis on overall survival. There were 414 patients (61.7 %) who had lymph node metastases. The overall 5-year survival rate was 54.7 %. There were no significant differences in survival among N2, N3, and M1 patients. Cox regression analysis revealed that common hepatic or splenic node involvements (P = 0.001), pT stage (P = 0.0002), and pN stage (P < 0.0001) were independent predictors of survival, but supraclavicular node involvement (P = 0.29) was not. We propose a modified nodal status that designates supraclavicular node as regional: m-N0 (5-year survival = 79 %; n = 251); m-N1 (5-year = 56 %; n = 212); m-N2 (5-year = 30 %; n = 114); m-N3 (5-year = 18 %; n = 52); m-M1 (5-year = 6.2 %; n = 36). This modified nodal staging predicts survival better than the current staging system. The modification of supraclavicular lymph node from nonregional to regional in the 7th UICC classification of ESCC may allow for better stratification of overall survival.


Neutralisation of Trichoplusia ni nuclear polyhedrosis virus with antisera to two forms of the virus.
Two forms of a baculovirus, Trichoplusia ni nuclear polyhedrosis virus, one released at the plasma membrane of cells (cell released virus: CRV) and the other derived from polyhedra (polyhedron derived virus: PDV) occur naturally. Antisera raised against the two forms specifically neutralised the homologous form. The envelope proteins of the two forms were shown to be the major proteins involved in serum neutralisation and to be responsible for the antigenic diversity of the virus forms.


Relationship Between Fear of Falling and Physical Activity in People Aging With a Disability.
An estimated one billion people worldwide live with some form of disability and may face many challenges as they age, including increased fall risk. Understanding the risk factors linking falls, fear of falling, and activity restriction is critical for developing effective programs to increase activity levels among persons with disabilities. To determine if differences exist in the level of physical activity in people with different types of conditions associated with disability and to investigate if fear of falling is associated with physical activity in individuals who are aging with a long-term disability. Cross-sectional retrospective design. Community. A convenience sample of 1812 community-dwelling individuals who had one of four diagnoses: multiple sclerosis (MS), muscular dystrophy (MD), spinal cord injury (SCI), or post-polio syndrome (PPS). Descriptive statistics, chi-square, and analysis of variance, followed by multivariate linear regression analysis were used to examine the association between physical activity status and fear of falling. Physical activity volume and fear of falling. After controlling for age, sex, duration of disability, and mobility level, there was variation across diagnostic groups (P < .001). People with SCI reported greater physical activity (M = 25.19) compared to other groups (MS: M = 18.70; MD: M = 21.83; PPS: M = 15.47). Patients with PPS had the greatest concerns about falling (M = 16.08), and patients with MS had the lowest (M = 13.12). Fear of falling was associated with physical activity (P < .001), which remained significant after controlling for diagnosis type, falls history, and level of mobility. Level of physical activity appears to vary among disability diagnoses. These results highlight the importance of addressing fear of falling in people with long-term disability because fear of falling is associated with physical activity.


Correcting a block?: successful experience of a small British pacing centre.
The establishment of a local permanent pacemaker service in a district general hospital increased the pacemaker implantation rate from 22 per million population per year to 152 per million population per year over the first 6 years of the service. Forty eight per cent of patients were referred by general practitioners and 52% by hospital specialists. Single chamber demand pacing (VVI) was used exclusively. Indications for pacing and complications were comparable to those of specialist cardiac centres. Management of symptomatic bradycardia by cardiac pacing in the United Kingdom may be facilitated by further development of small pacing centres.


Urine glycosaminoglycans in a reference population: effects of age, body surface area, and postmenopausal status.
Urine glycosaminoglycans and hydroxyproline have been measured in an adult reference population containing significant numbers of those over 65 years. Urine concentrations of glycosaminoglycans remain constant into old age providing body weight is maintained and correlate significantly with body surface area. The urine ratio of glycosaminoglycans to creatinine rises markedly in women after menopause resulting in a bimodal frequency distribution. This ratio is worth further investigation as a marker of postmenopausal osteoporosis.


Antibody response three months after SARS-CoV-2 infection.
The coronavirus disease-19 (COVID-19) pandemic became the greatest public health challenge globally. In our study, it was aimed to determine the antibody levels in the third month after the COVID-19 infection and the symptoms that continued until the third month from the onset of the infection. One hundred people who applied to Tarsus State Hospital with the suspicion of COVID-19 and were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by real-time reverse transcriptase-polymerase chain reaction were included. We collected serum samples from individuals, who were 3 months postinfection, and tested them in anti-SARS-CoV-2 Quanti-Vac ELISA IgG kit coated with recombinant S1 antigen for testing SARS-CoV-2 antibodies. Antibody levels were found to be higher in those aged ≥55 years, nonsmokers, those with comorbidities, and those who were hospitalized. The four most common symptoms that individuals initially encounter; are weakness, muscle and joint pain, loss of taste and smell, and cough. In 3 months after COVID-19 infection, the most common four symptoms are; muscle and joint pain, insomnia, fatigue, and other problems were determined. In conclusion; more research is needed to determine threshold levels of serum antibodies that could prevent reinfection of SARS-CoV-2.


Expression of trophic factors receptors during reinnervation after recurrent laryngeal nerve injury.
An injury of the recurrent laryngeal nerve (RLN) triggers axonal regeneration but results in a poor functional recovery. Netrin-1 and glial cell-derived neurotrophic factor (GDNF) expression are up-regulated in laryngeal muscles during RLN regeneration, but the role of their receptors produced in the nucleus ambiguus is unknown. The aim of this work was to determine the timing of the production of Netrin-1 and GDNF receptors during RLN regeneration and correlate this with the previously identified timing of up-regulation of their trophic factors in the laryngeal muscles. Laboratory experiment with rat model. The right RLN was transected and dextran amine tracer applied. At 7, 14, and 21 days postinjury (DPI), brainstems were removed and harvested. Immunostaining was performed for Netrin-1 (deleted in colorectal carcinoma [DCC], UNC5A) and GDNF receptors (rearranged during transfection [Ret], glycosylphosphatidylinositol-linked cell surface receptors [GFRα1, GFRα2, GFRα3]). The timing and type of receptor production relative to injury as well as their position in the nucleus ambiguus was analyzed. Netrin-1 UNC5A receptors were minimal in the nucleus ambiguus during RLN regeneration. DCC, the receptor that plays an attract role, was immunopositive from 7 to 21 DPI. All GDNF receptors, except GFRα2, were clearly positive from 7 to 14 DPI. No differences of production were observed according to the position of the motor neurons in the nucleus ambiguus. An injury of the RLN leads to a higher production of Netrin-1 DCC and GDNF receptors in the nucleus ambiguus. The timing of receptor production is similar to up-regulation of their trophic factors in the laryngeal muscles. NA. Laryngoscope, 129:2537-2542, 2019.


Is the Chinese medicinal formula Guipi Decoction () effective as an adjunctive treatment for depression? A meta-analysis of randomized controlled trials.
To evaluate the effectiveness and safety of Guipi Decoction (, GPD) as an adjunctive in the treatment of depression. A review of all relevant studies retrieved from a search of the following databases were conducted without any language restriction: Excerpt Medica Database (EMBASE), PubMed, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), VIP Information, Wanfang Data, and the Chinese Biomedical Literature Database. Papers published until February 2013 were taken into consideration. The analysis was performed using the Cochrane software Revman 5.1. Nine randomized controlled trials involving 620 patients with depression were included in this review. The meta-analysis revealed that compared with antidepressant therapy alone, treatment with a combination of GPD and an antidepressant drug signifificantly improved the symptoms of depression [weighted mean difference (WMD):-3.09; 95% confifidence interval (CI):-4.11 to-2.07] and increased the rates of effectiveness (OR: 4.75; 95% CI: 2.66-8.51) as well as recovery (OR: 1.73; 95% CI: 1.17-2.56). The adverse effects of GPD were not found to be signifificant in these studies. The fifindings of this meta-analysis were in keeping with the notion that GPD formulations were effective in the treatment of depression without causing any serious adverse effects. However, currently available evidence was of low quality and therefore inadequate to justify a strong recommendation of using GPD formulations in the management of depression.


Severe weather event attribution: Why values won't go away.
We start by reviewing the complicated situation in methods of scientific attribution of climate change to extreme weather events. We emphasize the social values involved in using both so-called ″storyline″ and ordinary probabilistic or ″risk-based″ methods, noting that one important virtue claimed by the storyline approach is that it features a reduction in false negative results, which has much social and ethical merit, according to its advocates. This merit is critiqued by the probabilistic, risk-based, opponents, who claim the high ground; the usual probabilistic approach is claimed to be more objective and more ″scientific″, under the grounds that it reduces false positive error. We examine this mostly-implicit debate about error, which apparently mirrors the old Jeffrey-Rudner debate. We also argue that there is an overlooked component to the role of values in science: that of second-order inductive risk, and that it makes the relative role of values in the two methods different from what it first appears to be. In fact, neither method helps us to escape social values, and be more scientifically ″objective″ in the sense of being removed or detached from human values and interests. The probabilistic approach does not succeed in doing so, contrary to the claims of its proponents. This is important to understand, because neither method is, fundamentally, a successful strategy for climate scientists to avoid making value judgments.


Subcortical dementia. Frontal cortex hypometabolism detected by positron tomography in patients with progressive supranuclear palsy.
The dementia associated with progressive supranuclear palsy (PSP) is considered to be subcortical because the cerebral cortex, unlike the subcortical structures, is usually free from major neuropathological lesions; the characteristic symptoms point to a dysfunction of the prefrontal lobe. The regional cerebral metabolic rate of glucose (rCMR Glu) was studied by positron emission tomography and 18F-fluoro-2-deoxyglucose18FDG in 6 patients presumed to have PSP and was compared with values found in 8 control subjects of similar age. The results obtained showed a highly significant rCMR Glu decrease in the prefrontal cortex of our patients. The loss of several subcortical afferents to prefrontal cortex may be responsible for the frontal cortical hypometabolism present in PSP.


Risk factors for hepatitis C virus infection among blood donors in Beijing and implications for improving the pretesting donor screening process.
The objective was to determine risk factors of hepatitis C virus (HCV) infection in blood donors in Beijing. A cross-sectional study was conducted in a total of 112 volunteer blood donors at Beijing Red Cross Blood Center (BRCBC) who were identified between January 2002 and December 2003 due to isolated HCV antibody reactivity at a donor screening procedure. The donors were recalled and interviewed about possible risk factor history. Additional blood samples were tested in repeated enzyme immunoassay, recombinant immunoblot assay, and nested reverse transcription-polymerase chain reaction. Chi-square test, analysis of variance, and multivariate logistic regression analysis were conducted to examine associations between HCV serostatus and potential risk factors. Among donors identified with isolated HCV antibody reactivity at donor screening, the prevalence of confirmed HCV infection was 31.3 percent (95% confidence interval [CI], 22.0%-39.2%) and indeterminate HCV infection was 22.3 percent (95% CI, 14.7%-30.3%), and the negative prevalence was 46.4 percent (95% CI, 37.5%-56.1%). The confirmed HCV cases were more likely than the indeterminate HCV cases to have the histories of previous transfusion, plasma donation, and hepatitis infection or elevated alanine aminotransferase (ALT), whereas the HCV-negative subjects were least likely to have the above histories (p < 0.05). Histories of blood transfusion before 1995, plasma donation, previous hepatitis infection, or elevated ALT were risk factors for HCV infection among blood donors in Beijing.


LC determination of the diastereomers of 1-(beta-D-glucopyranosyl)phenobarbital in human urine.
The "product enantioselectivity" associated with the urinary excretion of the phenobarbital N-glucoside conjugates has not been determined previously. A liquid chromatography method using gradient elution was developed for quantifying both phenobarbital N-glucoside conjugates, phenobarbital, and p-hydroxyphenobarbital. Following a single oral dose of phenobarbital to male Caucasian and Oriental subjects, both phenobarbital N-glucoside conjugates were observed in the urine. In seven subjects, 3.3-10.6% of the phenobarbital dose was detected as a single phenobarbital N-glucoside (S configuration at the C-5 position of the barbiturate ring). The other phenobarbital N-glucoside diastereomer accounted for less than 1.5% of the phenobarbital dose. The urinary excretion of the major phenobarbital N-glucoside diastereomer paralleled the urinary excretion of phenobarbital and was comparable in both Caucasian and Oriental subjects. These results indicate a pronounced selectivity for the formation and/or urinary excretion of the phenobarbital N-glucosides.


Iron reduction and gley formation by nitrogen-fixing clostridia.
Studies on iron reduction and the mechanism of gley formation by nitrogen-fixing clostridia are reported. Up to 106 cells/g soil of anaerobic, nitrogen-fixing clostridia, capable of reducing iron (III)-oxide, were counted in samples taken from various top soils. In a gleyed subsoil as many as 105 bacteria per g soil, capable of reducing and fixing nitrogen, were enumerated using the most probable number technique. In general, the ratio of the auxotrophic iron reducing clostridia (glucose+yeast extract fermenters) to the prototrophic iron reducing flora (glucose fermenters) was found much larger in the top soil samples than in those derived from various gleyed subsoils.An enrichment method for the isolation of nitrogen-fixing, iron reducing clostridia of the butyric-butyl type is described. The iron reducing capacity of this type of clostridia as well as of Clostridium pasteurianum was determined quantitatively. Generally, the presence of soil or soil extract enhanced the amount of dissolved ferrous iron, both with butyric acid fermenters and with Cl. pasteurianum.When enriched iron reducing clostridia were incubated anaerobically under N2-atmosphere in a sterile, red-colored, lateritic type of soil with glucose, intense gleying occurred within a few days. Microscopic observations indicated the presence of sporeforming bacteria of the Clostridium butyricum type or related species.The biological and chemical mechanism of gley formation is discussed.


B16 melanoma development in black mice exposed to low-level microwave radiation.
The effect of low-level microwave exposure, 2,450 MHz, at a power density of 1 mW/cm2 and specific absorption rate of 1.2 mW/g, continuous waves (CW) or pulsed waves (PW), 2.5 h/day, 6 sessions/week until death (up to 690 h of irradiation), has been studied in black C57/6J mice with B16 melanoma. The results show that no significant effects are observed on tumor development or on survival times compared to controls, or between CW- and PW-treated animals.


Involvement of pertussis toxin-sensitive G-proteins in the hormonal inhibition of dihydropyridine-sensitive Ca2+ currents in an insulin-secreting cell line (RINm5F).
Adrenaline inhibits insulin secretion via pertussis toxin-sensitive mechanisms. Since voltage-dependent Ca2+ currents play a key role in insulin secretion, we examined whether adrenaline modulates voltage-dependent Ca2+ currents of the rat insulinoma cell line, RINm5F. In the whole-cell configuration of the patch-clamp technique, dihydropyridine- but not omega-conotoxin-sensitive Ca2+ currents were identified. Adrenaline via alpha 2-adrenoceptors inhibited the Ca2+ currents by about 50%. Somatostatin which also inhibits insulin secretion was less efficient (inhibition by 20%). The hormonal inhibition of Ca2+ currents was not affected by intracellularly applied cAMP but blocked by the intracellularly applied GDP analog guanosine 5'-O-(2-thiodiphosphate) and by pretreatment of cells with pertussis toxin. In contrast to adrenaline and somatostatin, galanin, another inhibitor of insulin secretion, reduced Ca2+ currents by about 40% in a pertussis toxin-insensitive manner. Immunoblot experiments performed with antibodies generated against synthetic peptides revealed that membranes of RINm5F cells possess four pertussis toxin-sensitive G-proteins including Gi1, Gi2, Go2, and another Go subtype, most likely representing Go1. In membranes of control but not of pertussis toxin-treated cells, adrenaline via alpha 2-adrenoceptors stimulated incorporation of the photo-reactive GTP analog [alpha-32P]GTP azidoanilide into pertussis toxin substrates comigrating with the alpha-subunits of Gi2, Go2, and the not further identified Go subtype. The present findings indicate that activated alpha 2-adrenoceptors of RINm5F cells interact with multiple G-proteins, i.e. two forms of Go and with Gi2. These G-proteins are likely to be involved in the adrenaline-induced inhibition of dihydropyridine-sensitive Ca2+ currents and in other signal transduction pathways contributing to the adrenaline-induced inhibition of insulin secretion.


Underweight Patients Are the Greatest Risk Body Mass Index Group for 30-Day Perioperative Adverse Events After Total Shoulder Arthroplasty.
Existing literature investigating the correlation of body mass index (BMI) with surgical complications has focused on those with elevated BMI. These investigations have reported mixed conclusions, possible because of insufficient power, poor controlling of confounding variables, and inconsistent definitions of BMI categories (eg, underweight, overweight, and varying classifications of obese). Few studies have considered complications of patients with low BMI. The aim of the current study was to analyze the spectrum of categories for BMI with 30-day perioperative adverse events after primary total shoulder arthroplasty (TSA) to better assess where along the BMI spectrum patients are at risk for complications. Patients undergoing elective TSA were abstracted from the National Surgical Quality Improvement Program (NSQIP) databases from 2005 to 2016. Patients were then aggregated into BMI categories, and 30-day adverse events were normalized to average risk of normal-weight subjects (BMI 18.5 to 24.9 kg/m2). Risk-adjusted multivariate regressions were performed, controlling for demographic variables and overall health. In total, 15,717 patients met the inclusion criteria. Underweight TSA patients (BMI < 18.5 kg/m2) had the greatest odds for multiple perioperative adverse events compared with any other BMI category. By multivariate analysis, underweight patients were more likely to experience any adverse event (odds ratio [OR] = 2.22, P = 0.034), serious adverse events (OR = 3.18, P = 0.004), or have postoperative infections (OR = 2.77, P = 0.012) within 30 days when compared with normal-weight patients. No significant difference was observed in these complications for elevated BMI categories when compared with normal-weight patients. Only underweight TSA patients were found to have higher rates of 30-day perioperative adverse events than normal BMI patients, unlike any overweight/obese category including the super morbidly obese. Underweight TSA patients were thus identified as an at-risk subpopulation of TSA patients who had not previously been described. Physicians and healthcare systems should give additional consideration to this fragile cohort because they often already do for those at the other end of the BMI spectrum. III.


Effects of Stress Relaxation Aging with Electrical Pulses on Microstructures and Properties of 2219 Aluminum Alloy.
To realize the high-efficiency and high-performance manufacture of complex high-web panels, this paper introduced electric pulse current (EPC) into the stress relaxation aging forming process of 2219 aluminum alloy and systematically studied the effects of EPC, stress, and aging time upon the microstructure and properties of 2219 aluminum alloy. It is discovered that: (a) EPC greatly enhanced the mechanical properties after stress relaxation aging and reduced the sensitivity of the yield strength for the initial stress under the aging system of 165 °C/11 h; (b) compared with general aging, stress relaxation aging instead delayed the aging process of 2219 aluminum alloy and greatly increased the peak strength value;


Quantitative informant- and self-reports of subjective cognitive decline predict amyloid beta PET outcomes in cognitively unimpaired individuals independently of age and APOE ε4.
Amyloid beta (Aβ) pathology is an Alzheimer's disease early hallmark. Here we assess the value of longitudinal self- and informant reports of cognitive decline to predict Aβ positron emission tomography (PET) outcome in cognitively unimpaired middle-aged individuals. A total of 261 participants from the ALFA+ study underwent [18F]flutemetamol PET and Subjective Cognitive Decline Questionnaire (SCD-Q) concurrently, and 3 years before scan. We used logistic regressions to evaluate the ability of SCD-Q scores (self and informant) to predict Aβ PET visual read, and repeated analysis of variance to assess whether changes in SCD-Q scores relate to Aβ status. Self-perception of decline in memory (odds ratio [OR] = 1.2), and informant perception of executive decline (OR = 1.6), increased the probability of a positive scan. Informant reports 3 years before scanning predicted Aβ PET outcome. Longitudinal increase of self-reported executive decline was predictive of Aβ in women (P = .003). Subjective reports of cognitive decline are useful to predict Aβ and may improve recruitment strategies.


Interaction between body mass index and blood pressure on the risk of vascular stiffness : A community-based cross-sectional study and implications for nursing.
This study aimed to analyze associations between body mass index (BMI) and vascular measurements (brachial ankle pulse wave velocity [baPWV] and ankle-brachial index [ABI]), whether blood pressure (BP) was involved in the relationship, and implications for nursing. A cross-sectional study was conducted, including 1,894 middle-aged and older adults who underwent routine health screening at a community medical center in the Zhangjiang community in Shanghai, China. Participants were divided into three groups based on BMI: normal weight (n = 1,202), overweight (n = 480), and obese (n = 212). Multivariate linear regression models and smooth curve fittings were used to evaluate the associations between BMI and indices of vascular stiffness. Mediation analysis examined whether blood pressure mediate the association between BMI and vascular stiffness. Multiple linear regression analysis showed that BMI to be significantly and negatively associated with baPWV (β = -0.06 [-0.10, -0.03]) and ABI (β = -0.004 [-0.005, -0.003]), respectively. The interaction test results of systolic blood pressure (SBP) in the relationship between BMI and baPWV were significant (P for interaction = 0.01). After adjusting for age and sex, mediation analyses showed that BMI and baPWV were correlated (β = 0.090, P < 0.001) and mediated by SBP (β = 0.533, P < 0.001) and diastolic blood pressure (DBP) (β = 0.338, P < 0.001). A negative association was found between BMI and ABI (β = -0.135, P < 0.001), which appeared to be partially mediated by SBP (β = 0.124, P < 0.001) and DBP (β = 0.053, P < 0.001). Additional subgroup analysis based on blood pressure levels did not revealed statistically significant mediating effects. Our findings showed conflicting associations between BMI and non-invasive vascular measurements of arterial stiffness. BP may have a biological interaction in the relationship between BMI and baPWV. Managing blood pressure and weight through comprehensive clinical care is crucial for preventing stiffness or blockage of vessels in middle-aged and older adults.


d-lactate-induced ETosis in cattle polymorphonuclear leucocytes is dependent on the release of mitochondrial reactive oxygen species and the PI3K/Akt/HIF-1 and GSK-3β pathways.
d-lactate is a metabolite originating from bacterial metabolism that accumulates as a result of dietary disturbances in cattle, leading to ruminal acidosis. d-lactate exerts functions as a metabolic signal inducing metabolic reprogramming and extracellular trap (ET) release in polymorphonuclear leucocytes (PMNs). We previously demonstrated that d-lactate induces metabolic reprogramming via hypoxia-induced factor 1 alpha (HIF-1α) stabilization in bovine fibroblast-like synoviocytes (FLSs). In the present study, the role of HIF-1 in ET formation induced by d-lactate was assessed. HIF-1α stabilization in PMNs was controlled by mitochondrial reactive oxygen species (mtROS) release. Furthermore, inhibition of mitochondrial complex I and scavenging of mtROS decreased d-lactate-triggered ETosis. d-lactate-enhanced HIF-1α accumulation was dependent on the PI3K/Akt pathway but independent of GSK-3β activity. Pharmacological blockade of the PI3K/Akt/HIF-1 and GSK-3β axes inhibited d-lactate-triggered ETosis and downregulated PDK1 and LDHA expression. However, only GSK-3β inhibition decreased the expression of glycogen metabolism enzymes and prevented the decline in glycogen stores induced by d-lactate exposure. The results of this study suggest that mtROS, PI3K/Akt/HIF-1 and GSK-3β axes regulate carbohydrate metabolism adaptations that support d-lactate-induced ET formation in cattle.


Gestational diabetes affects postnatal development of transport and enzyme functions in rat intestine.
The effect of alloxan-induced gestational diabetes on the postnatal development of brush border disaccharidases and D-glucose transport in rat intestine was studied. Pups born to diabetic mothers showed 92-22% increase in blood sugar levels compared with the controls. Western blot and RT-PCR analyses revealed that the activities of brush border sucrase, lactase and Sodium Glucose Co-transporter 1 (SGLT1) correlates with protein and mRNA levels in intestine of pups born to diabetic rat mothers after 5-45 days of birth. Intestinal histology in pups born to diabetic mothers at day 10 and 45 after birth showed distorted cellular organization of mucosa with a decrease in the number of secretary goblet cells and regression of tubular mass. These findings suggest that the genetic switch in utero regulates the postnatal expression of enzyme and transport functions in intestine of pups born to diabetic rat mothers. This may influence the growth and development of offsprings later in life.


Fasciculoventricular pathways-A rare and innocent variant: A Retrospective study focusing on clinical and electrophysiologic characteristics.
Fasciculoventricular pathways (FVPs) are variants of pre-excitation syndrome which were investigated insufficiently because of its rarity. This report aimed to represent one of the largest series of FVP, focusing on its clinical and electrophysiological properties. We analyzed retrospectively 26 consecutive patients who underwent electrophysiological study (EPS) for FVP between January 1998 and June 2020. Among 1437 patients with accessory pathways, 26 had FVP (1.80%). All the 26 patients (100%) were males, with a mean age of 22.15 ± 3.50 years (range, 20-34 years). In the baseline electrocardiograms of the patients with FVP, pre-excitation and transitional zone were seen in leads V2 -V4 . During EPS procedures, normal AH interval and shortened HV interval were detected. All the patients had AH prolongation after atrial pacing due to atrioventricular (AV) nodal delay without change in pre-excitation degree. Five of the FVP patients (19.2%) had extra accessory pathways, all of which were ablated successfully while the FVPs were followed clinically. Fasciculoventricular pathways are uncommon variants of pre-excitation syndrome; therefore, they should be diagnosed correctly and followed up noninvasively to avoid damages.


Determination of trace mercury in water based on N-octylpyridinium ionic liquids preconcentration and stripping voltammetry.
A novel method for determination of trace mercury in water is developed. The method is performed by extracting mercury firstly with ionic liquids (ILs) and then detecting the concentration of mercury in organic media with anodic stripping voltammetry. Liquid-liquid extraction of mercury(II) ions by four ionic liquids with N-octylpyridinium cations ([OPy](+)) was studied. N-octylpyridinium tetrafluoroborate and N-octylpyridinium trifluoromethylsulfonate were found to be efficient and selective extractant for mercury. Temperature controlled dispersive liquid phase microextraction (TC-DLPME) technique was utilized to improve the performance of preconcentration. After extraction, precipitated IL was diluted by acetonitrile buffer and mercury was detected by differential pulse stripping voltammetry (DPSV) with gold disc electrode. Mercury was enriched by 17 times while interfering ions were reduced by two orders of magnitude in the organic media under optimum condition. Sensitivity and selectivity for electrochemical determination of mercury were improved by using the proposed method. Tap, pond and waste water samples were analyzed with recoveries ranging from 81% to 107% and detection limit of 0.05 μg/L.


Significance of investigating allelopathic interactions of marine organisms in the discovery and development of cytotoxic compounds.
Marine sessile organisms often inhabit rocky substrata, which are crowded by other sessile organisms. They acquire living space via growth interactions and/or by allelopathy. They are known to secrete toxic compounds having multiple roles. These compounds have been explored for their possible applications in cancer chemotherapy, because of their ability to kill rapidly dividing cells of competitor organisms. As compared to the therapeutic applications of these compounds, their possible ecological role in competition for space has received little attention. To select the potential candidate organisms for the isolation of lead cytotoxic molecules, it is important to understand their chemical ecology with special emphasis on their allelopathic interactions with their competitors. Knowledge of the ecological role of allelopathic compounds will contribute significantly to an understanding of their natural variability and help us to plan effective and sustainable wild harvests to obtain novel cytotoxic chemicals. This review highlights the significance of studying allelopathic interactions of marine invertebrates in the discovery of cytotoxic compounds, by selecting sponge as a model organism.


In Vitro Amplification of Pathogenic Tau Seeds from Neurodegenerative Disease Patient Brains.
Aggregated microtubule-associated protein tau (tau) is the hallmark lesion of a group of neurodegenerative diseases, termed tauopathies. Normal endogenous tau is highly soluble and intrinsically disordered when it is not bound to microtubules. Pathological tau proteins are aggregates of bioactive filaments capable of inducing their normal counterparts into pathological conformations that are human tauopathy dependent. Taking advantage of this feature, we established an in vitro seeding reaction to amplify faithfully human-derived tau strains. This approach allows us to expand the quantity and improve the quality of pathogenic tau strains derived from human patient postmortem brains and to further understand tau pathogenesis in models of tauopathy. Here, we describe the approach to generate human pathogenic tau using human-derived tau seeds and recombinant human tau in vitro.


Initial-onset acute and chronic recurrent stages are two distinctive courses of Vogt-Koyanagi-Harada disease.
To describe distinctive stages of Vogt-Koyanagi-Harada (VKH) disease: initial-onset acute versus chronic recurrent disease. A comprehensive literature review regarding stages and clinical presentations of VKH disease was conducted. Despite a list of signs that has been described as characteristic features of early or late phases of VKH disease, the current classification -developed by an international committee and published in 2001- does not consider a distinction regarding the time from onset of disease symptoms, and specific findings observed at certain time point from the symptoms presentation and outcomes related to the stage of VKH disease. In that sense, chronic recurrent VKH disease is more refractory to treatment and is associated with a higher rate of complications. Accordingly, this subset of VKH patients has poorer functional and anatomical outcomes than patients with an initial-onset acute disease. An early clear distinction of VKH phenotype [Initial-onset acute versus chronic recurrent disease] should be considered in each clinical scenario, evaluating the delay in diagnosis and the clinical presentation, since it may help clinicians to perform a correct disease prognosis categorization and thus to make treatment decisions in terms of potential refractoriness or expected clinical outcomes.


Computational experience with an algorithm for tetrangle inequality bound smoothing.
An important component of computer programs for determining the solution conformation of proteins and other flexible molecules from nuclear magnetic resonance data are the so-called "bound smoothing algorithms", which compute lower and upper limits on the values of all the interatomic distances from the relatively sparse set which can usually be measured experimentally. To date, the only methods efficient enough for use in large problems take account of only the triangle inequality, but an appreciable improvement in the precision of the limits is possible if the algebraic relations between the distances among each quadruple of atoms are also considered. The goal of this paper is to use a recently improved algorithm for computing these "tetrangle inequality limits" to determine just how much improvement really is possible, given the types of experimental data that are usually available.


Screening potential hypertensive peptides using two consecutive bioassay-guided SPE fractionations and identification of an ACE inhibitory peptide, DHSTAVW (DW7), derived from pearl garlic protein hydrolysate.
The pearl garlic (Allium sativum L.) protein (PGP) was digested using pepsin, trypsin, α-chymotrypsin, thermolysin, and simulated gastrointestinal digestion. The α-chymotrypsin hydrolysate showed the highest angiotensin-I-converting enzyme inhibitory (ACEI) activity, with an IC50 value of 190.9 ± 11 µg/mL. A reversed-phase C18 solid-phase extraction (RP-SPE) cartridge was used for the first fractionation, and the S4 fraction from RP-SPE showed the most potent ACEI activity (IC50 =124.1 ± 11 3 µg/mL). The S4 fraction was further fractionated using a hydrophilic interaction liquid chromatography SPE (HILIC-SPE). The H4 fraction from HILIC-SPE showed the highest ACEI activity (IC50 =57.7 ± 3 µg/mL). Four ACEI peptides (DHSTAVW, KLAKVF, KLSTAASF, and KETPEAHVF) were identified from the H4 fraction using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and their biological activities were appraised in silico. Among the identified α-chymotryptic peptides, DHSTAVW (DW7), derived from I lectin partial protein, exhibited the most potent ACEI activity (IC50 value of 2.8 ± 0.1 µM). DW7 was resistant to simulated gastrointestinal digestion, and it was classified as a prodrug-type inhibitor according to the preincubation experiment. The inhibition kinetics indicated that DW7 was a competitive inhibitor, which was rationalized by the molecular docking simulation. The quantities of DW7 in 1 mg of hydrolysate, S4 fraction, and H4 fraction were quantified using LC-MS/MS to give 3.1 ± 0.1, 4.2 ± 0.1, and 13.2 ± 0.1 µg, respectively. The amount of DW7 was significantly increased by 4.2-fold compared with the hydrolysate, which suggested that this method is efficient for active peptide screening.


Beta-amyloid-activated cell cycle in SH-SY5Y neuroblastoma cells: correlation with the MAP kinase pathway.
Primary cultures of rat cortical neurons exposed to toxic concentrations of beta-amyloid peptide (betaAP) begin an unscheduled mitotic cell cycle that does not progress beyond the S phase. To analyze possible signal transduction pathways involved in this effect, the action of betaAP has been studied in SH-SY5Y neuroblastoma cells differentiated by a 7-d exposure to 10 microM retinoic acid. Treatment with the betaAP fragment, betaAP(25-35), (25 microM) for 24, 48, or 72 h caused apoptotic cell death, detected by flow cytometry as a prediploid cell population. Cell cycle analysis showed that betaAP(25-35) modified cell cycle profiles by markedly increasing the number of cells in the S phase and reducing the population of the G2/M area. These effects seem to involve activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK1/2). Inhibition of this pathway by the specific inhibitor PD98059 (2 microM) completely prevented changes of cell cycle distribution induced by betaAP and significantly reduced neuronal death. The data suggest that MAPK cascade can mediate the induction of cell cycle induced by betaAP, thus contributing to the toxicity of the peptide.


Effect of gene polymorphisms on the mechanical properties of human tendon structures.
Recent studies showed that polymorphisms in alpha 1 chains of types I (COL1A1) and V (COL5A1) collagen, growth and differentiation factor 5 (GDF5), and matrix metalloproteinase 3 (MMP3) genes were associated with injuries in tendons and ligaments (e.g., September et al. (Br J Sports Med 43: 357-365 2009)). In the present study, we aimed to investigate the effects of injury-associated polymorphisms within these four genes on the mechanical properties of human tendon structures in vivo. One hundred Japanese males participated in this experiment. The mechanical properties of tendon structures in knee extensors and plantar flexors were measured using ultrasonography. All subjects were genotyped for COL1A1 rs1800012, COL5A1 rs12722, GDF5 rs143383, and MMP3 rs679620 single nucleotide polymorphisms. For COL1A1, all subjects had a GG genotype. For COL5A1, maximal tendon elongation and strain of individuals with a CC genotype were significantly greater than individuals with other genotypes (combined TT and CT) for knee extensors, but not for plantar flexors. For GDF5 and MMP3, there were no differences in the mechanical properties of tendon structures in knee extensors and plantar flexors among the three genotypes. The present study demonstrated that subjects with a CC genotype of the COL5A1 gene had more extensible tendon structures than those of subjects with other genotypes (combined TT and CT) for knee extensors, but not for plantar flexors. The results presented in this study need to be confirmed in a larger cohort of subjects.


Improved competitive enzyme-linked immunoassay (ELISA) for albuminuria.
Microalbuminuria has been established as a marker strongly predictive of diabetic nephropathy. The appearance of microalbuminuria (30-150 micrograms/min) is considered to herald incipient nephropathy, and the progression to clinical proteinuria (greater than 200 mg/24 h) is believed to reflect a shift from reversible to irreversible renal damage in diabetic patients. Periodic monitoring of albumin excretion could thus detect diabetic renal disease at an early, potentially reversible stage. However, this is not routinely done, largely due to cumbersome collection and methodologic constraints. We therefore have developed a simplified competitive immunoassay (ELISA) that is sensitive to 10 ng and reproducibly quantifies urinary albumin levels between 0.1-10 micrograms/ml, a range appropriate to that demarcating normal from microalbuminuric patients. Examination of results obtained with aliquots of 24 h and fractional urine collections, without and with correction for creatinine (albumin: creatine ratio), in basal and post-exercise states indicates that (a) this assay can effectively measure urine albumin concentration in single void specimens, and albumin excretion rates in fractional collections, and (b) conversion to albumin:creatinine ratio is not necessary to discriminate normal from microalbuminuric states.


Divergent expression of cytotoxic and microbicidal functions of rabbit alveolar and peritoneal macrophages: effects of non-specific activation and a natural microbicidal peptide, MCP-1.
Alveolar macrophages from NZW rabbits were intrinsically toxic to 6 xenogeneic cell lines and to Candida albicans in vitro. Macrophage-mediated candidacidal activity, but not cytostasis (inhibition of [3H] thymidine incorporation by target cells) or cytotoxicity (reduction in target cell number), was enhanced by prior injection of rabbits with Freund's complete adjuvant (FCA). Compared with alveolar macrophages, peritoneal macrophages were less candidacidal (median C. albicans killed, 24% versus 16%, p less than 0.01). In contrast to alveolar macrophages, peritoneal macrophages were not consistently cytostatic or cytotoxic. Only candidacidal activity was enhanced in FCA-elicited peritoneal macrophages (median C. albicans killed 28% versus 16% for resident peritoneal macrophages, p less than 0.01). Microbicidal concentrations of a cationic peptide produced by rabbit alveolar macrophages (MCP-1, 25-100 micrograms/ml) did not inhibit growth of 4 murine cell lines in vitro. Macrophage-mediated cytostasis and cytotoxicity were not enhanced by culture with exogenous MCP-1. Macrophage-mediated cytostasis was also unchanged in cultures containing 10(-5) 2' deoxycytidine. We conclude that rabbit macrophage populations are restricted in their expression of cytostatic and cytotoxic functions, that microbicidal activation can occur independently of cytotoxic activation and that in this system mechanisms of macrophage-mediated cytotoxicity to xenogeneic target cells are independent of MCP-1 and thymidine.


Formalin fixed brains are useful for magnetic resonance imaging (MRI) study.
We carried out magnetic resonance imaging (MRI) studies on human brains which had been fixed in formalin solution for over 2 years and had been proven neuropathologically to be cases of multiple sclerosis (MS), progressive multifocal leukoencephalopathy (PML), and Balo's concentric sclerosis (Balo). Using spin echo (SE) and inversion recovery (IR) pulse sequences to detect demyelinated lesions in a living person with MS, the demyelinated lesions of the fixed brains in cases of MS, PML and Balo definitely re-appeared, although T1 and T2 in the gray and white matter were reduced following fixation. High signal areas on the SE images corresponded not only to the characteristic distribution of demyelinated lesions in the white matter but also to sparse myelin, gliosis and mild perivascular cuffing in the white matter around the demyelinated foci in cases of the fixed MS, PML and Balo brains. On the IR images, only MS plaques were evident. This MRI study of fixed brains proved useful to elucidate clinicopathological correlations.


The Chicken cGAS-STING Pathway Exerts Interferon-Independent Antiviral Function via Cell Apoptosis.
It has been recently recognized that the DNA sensing innate immune cGAS-STING pathway exerts an IFN-independent antiviral function; however, whether and how chicken STING (chSTING) exerts such an IFN-independent antiviral activity is still unknown. Here, we showed that chSTING exerts an antiviral activity in HEK293 cells and chicken cells, independent of IFN production. chSTING was able to trigger cell apoptosis and autophagy independently of IFN, and the apoptosis inhibitors, rather than autophagy inhibitors, could antagonize the antiviral function of chSTING, suggesting the involvement of apoptosis in IFN-independent antiviral function. In addition, chSTING lost its antiviral function in IRF7-knockout chicken macrophages, indicating that IRF7 is not only essential for the production of IFN, but also participates in the other activities of chSTING, such as the apoptosis. Collectively, our results showed that chSTING exerts an antiviral function independent of IFN, likely via apoptosis.


Effective degradation of anthraquinones in Folium Sennae with Monascus fermentation for toxicity reduce and efficacy enhancement.
Folium Sennae are widely used around the world, mainly in purging and removal of endogenous active substances, such as anthraquinone and its derivatives. However, the potential toxicity of anthraquinones to the liver, kidney, and intestinal limits the application of Folium Sennae. In this study, we aimed at safe regulation of Folium Sennae to degrade anthraquinones, boosting medicinal properties and reducing toxicity and potency with Monascus fermentation. Monascus strains H1102 for Folium Sennae fermentation were selected as the initial strain which was capable of producing high yields of functional pigment and low yields of hazardous citrinin. The anthraquinone degradation rate reached 41.2%, with 212.2 U mL-1 of the pigment and approximately 0.038 mg L-1 of the citrinin under optimal fermentation conditions followed by response surface streamlining, which met the requirements of reducing toxicity, increasing efficiency of Monascus fermented Folium Sennae. Furthermore, the Monascus/Folium Sennae culture had no observable toxic effect on HK-2 and L-02 cells in vitro and further inhibited cell apoptosis and necrosis. Overall, our results showed that Monascus fermentation could provide an alternative strategy for toxicity reduction of herbal medicines as well as efficacy enhancement.


Impact of COVID-19 on Liver Transplant Activity in the USA: Variation by Etiology and Cirrhosis Complications.
The COVID-19 pandemic has impacted the care of patients with liver disease. We examined impact of COVID-19 on liver transplant (LT) activity in the USA. LT listings in the United Network for Organ Sharing (UNOS) database (April 2018-May 2021) were analyzed to examine the impact of COVID-19 pandemic on the LT activity based on etiology: hepatitis C virus (HCV), alcohol-associated liver disease (ALD), alcoholic hepatitis (AH), and nonalcoholic steatohepatitis (NASH) complications: hepatocellular carcinoma (HCC) and acute-on-chronic liver failure (ACLF) grade 2 or 3) and Model for End-Stage Liver Disease (MELD) score. Joinpoint regression models assessed time trend changes on a log scale. Of 23,871 recipients (8,995 in the COVID era, April 2018-February 2020), mean age 52 years, 62% men, 61% Caucasian, 32% ALD, 15% HCC, 30% ACLF grades 2-3, and mean MELD score 20.5), monthly LT changes were a decrease of 3.4% for overall LTs and 22% for HCC after September 2020, and increase of 4.5% for ALD since 11/2020 and 17% since 03/2021 for ACLF grade 2-3. Monthly MELD scores increased by 0.7 and 0.36 after June 2020 for HCV and HCC respectively. The COVID-19 pandemic has impacted LT activity, with a decrease of LTs especially for HCC, and an increase of LTs for ALD and severe ACLF. Strategies are needed to reorganize cirrhosis patients to overcome the aftereffects of COVID-19 pandemic.


The More, the Merrier: DC3s Join the Human Dendritic Cell Family.
Recent studies have reported additional subpopulations of human dendritic cells (DCs), but whether they are distinct subsets has been unclear. In this issue of Immunity, Cytlak et al. and Bourdely et al. show that DC3s possess a specific precursor and represent a separate DC lineage.


Mechanism of histamine release from isolated mast cell granules by calcium with phosphatidyl serine.
Histamine is released from isolated mast cell granules with intact membranes by calcium (10 mM) in presence of phosphatidyl serine (25-50 micrograms/ml). The release occurs both in Krebs-Ringer solution and in sucrose solution without monovalent cations, but the release in Krebs-Ringer solution is somewhat higher. The histamine release is associated with increased calcium uptake. But calcium is taken up much faster, within 5 sec, while it takes several minutes before histamine release is completed. The observations suggest a rapid uptake of calcium to the granule membrane, from which it may be more slowly released to the matrix, displacing histamine from its binding sites. Phosphatidyl serine with calcium could also conceivably change the membrane permeability causing increased influx of sodium ions, thus accounting for the mild enhancement of the release in Krebs-Ringer solution.


Linguistic labels: conceptual markers or object features?
Linguistic labels affect inductive generalization; however, the mechanism underlying these effects remains unclear. According to one similarity-based model, SINC (similarity, induction, naming, and categorization), early in development labels are features of objects contributing to the overall similarity of compared entities, with early induction being similarity based. If this is the case, then not only identical but also phonologically similar labels may contribute to the overall similarity and thus to induction. These predictions were tested in a series of experiments with 5-year-olds and adults. In Experiments 1-5 participants performed a label extension task, whereas in Experiment 6 they performed a feature induction task. Results indicate that phonological similarity contributes to early induction and support the notion that for young children labels are features of objects.


Avoidant Coping and Poor Sleep Efficiency in Dementia Caregivers.
Caring for a spouse with dementia is a source of chronic stress and is associated with a heightened prevalence of self-reported sleep problems. Styles and strategies for coping with stress have been associated with objective measures of sleep in non-caregiver populations. The current study evaluated relationships between caregiver coping style and sleep disturbance using in-home polysomnography. Sixty spousal caregivers (mean [standard deviation] age = 73.31 [7.05] years; 81.7% female) completed the Brief Cope, the Hamilton Rating Scale for Depression, and three nights of in-home polysomnography. Participants were categorized into two groups based on the presence or absence of clinically significant low sleep efficiency (<80%). A factor analysis of the Brief Cope yielded higher-order factors that included approach coping and avoidant coping (explained variance, 27.2% and 16.9%, respectively). Coping factors were entered into a binary logistic regression predicting sleep efficiency group while controlling for sleep apnea, medication use, and depression, as measured by the Hamilton Rating Scale for Depression. In fully adjusted models, for each unit increase on the avoidant coping factor, participants were 3.4 times more likely to be classified in the low sleep efficiency group (B = 1.224, χ2(1) = 4.967, p = .026, exp(B) = 3.401, 95% confidence interval = 1.159-9.981). Approach coping was unrelated to sleep efficiency in both adjusted and unadjusted models. These findings highlight the importance of coping among caregivers and indicate that avoidant coping may be a modifiable predictor of sleep disturbance in conditions of chronic stress.


Two distinct (-)nicotine binding sites in goldfish brain. Identification and characterization of putative neuronal nicotinic acetylcholine receptor subtypes.
The binding of (-)-[3H]nicotine to membrane fragments and a detergent solubilized fraction of goldfish brain was characterized. (-)-[3H]nicotine binding was not displaced by alpha-bungarotoxin, but was displaced by (-)nicotine and carbamoylcholine with Ki of approximately 8.6 and 86 nM, respectively. Preincubation of solubilized membrane extract with alpha-bungarotoxin-coupled Sepharose resulted in the loss of approximately 50% of the (-)-[3H]nicotine binding protein from the eluent and an increase in (-)-[3H]nicotine binding to the gel compared to control, non-alpha-bungarotoxin Sepharose. 125I-alpha-bungarotoxin binding protein in the eluent from the same preincubation experiments was totally removed. In addition, incubation of the solubilized tissue extracts with alpha-bungarotoxin-coupled Sepharose resulted in an increase in the affinity for (-)-[3H]nicotine in the eluent (mean KD = 3.1) compared to control solubilized tissue extracts (KD = 6.4 nM). Specific (-)-[3H]nicotine binding sites could be eluted from the alpha-bungarotoxin-coupled Sepharose with carbamoylcholine and D-tubocurarine. Similar to previously reported 125I-alpha-bungarotoxin binding data, eye removal resulted in an approximately 40% decrease in (-)-[3H]nicotine binding in the contralateral tectum compared to that in the ipsilateral tectum. These data indicate that at least two distinct subtypes of (-)nicotine binding sites may be present in goldfish brain, one which binds alpha-bungarotoxin and (-)nicotine and another which binds only (-)nicotine.


Rods and cones activate different excitatory amino acid receptors on the mudpuppy retinal horizontal cell.
We have studied rod and cone neurotransmission onto horizontal cells (HCs) of the mudpuppy retina by: (1) dual whole-cell recordings from synaptically connected pairs in a superfused retinal slice preparation, and (2) intracellular recordings from HCs in a superfused retina-eyecup preparation. In the presence of relatively weak concentrations of broad spectrum excitatory amino acid antagonists, HC recordings show that cone-mediated responses were significantly more attenuated than those mediated by rods. These observations suggest that the HC postsynaptic receptors for rods and cones are pharmacologically different. One advantage of having distinct rod- and cone-activated receptors on second-order neurons may be to preserve different rod and cone functions under varying levels of light stimulation and provide separate means of regulating rod and cone neurotransmission onto the second-order cells.


Knockout of P-glycoprotein abolish the collateral sensitivity of CHORC5 multidrug resistant cells.
Multidrug resistant tumor cells show collaterally sensitive to a range of non-toxic drugs. In this report, we describe the isolation of several P-glycoprotein-knockout cell clones, using CRISPR/Cas9, from Chinese hamster multidrug resistant model cell line and its parental cells (e.g., CHORC5 and AuxB1, respectively). All three P-glycoprotein-knockout clones of CHORC5 cells show complete loss of resistance to anti-cancer drugs (e.g., colchicine and doxorubicin), while gaining resistance to well characterized collateral sensitivity drugs (e.g., verapamil, progesterone and NSC73306). A correlation between P-glycoprotein and Sorcin expression levels and a possible role for the latter in low grade resistance to colchicine and doxorubicin was observed. Furthermore, we show that P-glycoprotein expression is necessary for the ROS-mediated mechanism of collateral sensitivity. However, expectantly, P-glycoprotein-knockout clones of CHORC5 cells revealed a dramatic increase in the accumulation of Rhodamine 123, Mito tracker red and doxorubicin, but not Hoechst 33342. The latter findings and their significance to P-glycoprotein collateral sensitivity remain to be determined.


Asymmetric dimethylarginine, L-arginine, and endothelial dysfunction in essential hypertension.
We investigated the relationship between ADMA plasma levels and endothelium-dependent vasodilation in 36 never-treated essential hypertensives and in 8 normotensive healthy subjects. It has been demonstrated that endothelium-dependent vasodilatation is impaired in essential hypertension. The potential contribution of asymmetric dimethylarginine (ADMA) to endothelial dysfunction of hypertensive humans has received poor attention. Endothelial function was measured during intra-arterial infusion of acetylcholine (ACh), alone and during co-infusion of L-arginine, and sodium nitroprusside at increasing doses. Concentrations of ADMA and L-arginine in plasma were measured by high-performance liquid chromatography. Hypertensive subjects had significantly higher ADMA and L-arginine plasma concentrations than normotensive healthy controls; ACh-stimulated forearm blood flow (FBF) was significantly reduced in hypertensive subjects in comparison to normotensive control subjects (p < 0.0001). Intra-arterial coinfusion of L-arginine induced a further significant enhancement in ACh-stimulated vasodilation in hypertensive patients. In these, ADMA was strongly and inversely associated with the peak increase in FBF. In a multivariate model, only ADMA and L-arginine were independent correlates, accounting for 33.9% and 8.9% of the variability in the peak FBF response to ACh (p < 0.0001), respectively. The main finding in this study is that in essential hypertensives the L-arginine and endogenous inhibitor of nitric oxide synthase, ADMA, are inversely related to endothelial function.


Transition from obesity to metabolic syndrome is associated with altered myocardial autophagy and apoptosis.
Transition from obesity to metabolic-syndrome (MetS) promotes cardiovascular diseases, but the underlying cardiac pathophysiological mechanisms are incompletely understood. We tested the hypothesis that development of insulin resistance and MetS is associated with impaired myocardial cellular turnover. MetS-prone Ossabaw pigs were randomized to 10 weeks of standard chow (lean) or to 10 (obese) or 14 (MetS) weeks of atherogenic diet (n=6 each). Cardiac structure, function, and myocardial oxygenation were assessed by multidetector computed-tomography and Blood Oxygen Level-Dependent-MRI, the microcirculation with microcomputed-tomography, and injury mechanisms by immunoblotting and histology. Both obese and MetS showed obesity and dyslipidemia, whereas only MetS showed insulin resistance. Cardiac output and myocardial perfusion increased only in MetS, yet Blood Oxygen Level-Dependent-MRI showed hypoxia. Inflammation, oxidative stress, mitochondrial dysfunction, and fibrosis also increased in both obese and MetS, but more pronouncedly in MetS. Furthermore, autophagy in MetS was decreased and accompanied by marked apoptosis. Development of insulin resistance characterizing a transition from obesity to MetS is associated with progressive changes of myocardial autophagy, apoptosis, inflammation, mitochondrial dysfunction, and fibrosis. Restoring myocardial cellular turnover may represent a novel therapeutic target for preserving myocardial structure and function in obesity and MetS.


Association between smoking, insulin resistance and beta-cell function in a North-western First Nation.
Aboriginal peoples have a high prevalence of smoking and are at major risk for diabetes. The role of insulin resistance vs. compromised beta-cell function in the link between smoking and glycaemic disease is not clear. This study tested whether relations between insulin resistance and beta-cell function differ between current smokers, former smokers and non-smokers, and if having diabetes modifies smoking-related effects. A community-based diabetes screening initiative was mounted for a North-western First Nation (Interior Salishan) in rural British Columbia, Canada. Respondents were on-reserve Aboriginal people (n=156), all adults 18+ years. Glycaemic status was determined by oral glucose tolerance test. Fasting values for glucose and insulin were used to estimate beta-cell function and insulin resistance by homeostasis model assessment (HOMA). Analyses adjusted for age, sex, alcohol intake, education, body mass index and physical activity. For normoglycaemic persons (n=119) current smokers relative to non-smokers had high beta-cell values [difference (95% confidence interval) 19.5 (17.1, 21.9)], while former smokers had low beta-cell values [difference -22.8 (-20.3, -25.3)] (P<0.0001). For diabetic persons (n=37) differences were of equivalent direction but greater magnitude (P<0.0001). Insulin resistance was for normoglycaemic persons highest for current smokers, and for diabetic persons lowest for current smokers (P=0.021). Former smoking is associated with low beta-cell function, and current smoking with high beta-cell function, independent of diabetes in the North-western First Nation surveyed. Associations between smoking and insulin resistance vary according to glycaemic status. Smoking may have diametric acute and post-cessation effects on beta-cell function and insulin resistance.


Robust Multiple Sclerosis Lesion Inpainting with Edge Prior.
Inpainting lesions is an important preprocessing task for algorithms analyzing brain MRIs of multiple sclerosis (MS) patients, such as tissue segmentation and cortical surface reconstruction. We propose a new deep learning approach for this task. Unlike existing inpainting approaches which ignore the lesion areas of the input image, we leverage the edge information around the lesions as a prior to help the inpainting process. Thus, the input of this network includes the T1-w image, lesion mask and the edge map computed from the T1-w image, and the output is the lesion-free image. The introduction of the edge prior is based on our observation that the edge detection results of the MRI scans will usually contain the contour of white matter (WM) and grey matter (GM), even though some undesired edges appear near the lesions. Instead of losing all the information around the neighborhood of lesions, our approach preserves the local tissue shape (brain/WM/GM) with the guidance of the input edges. The qualitative results show that our pipeline inpaints the lesion areas in a realistic and shape-consistent way. Our quantitative evaluation shows that our approach outperforms the existing state-of-the-art inpainting methods in both image-based metrics and in FreeSurfer segmentation accuracy. Furthermore, our approach demonstrates robustness to inaccurate lesion mask inputs. This is important for practical usability, because it allows for a generous over-segmentation of lesions instead of requiring precise boundaries, while still yielding accurate results.


'Balancing acts': the politics and processes of smokefree area policymaking in a small state.
To examine the influences on contemporary smokefree area policy development in New Zealand. Semi-structured interviews were conducted with 62 New Zealand politicians and senior officials. They were asked about their views of possible interventions to reduce smoking around children, and how to achieve progress on smokefree homes, cars and public places. Transcribed data were analysed for themes, some of which were determined by the questions asked, and some emerged from the dynamic nature of the interviews. Policymaking for smokefree areas was seen by participants as a complex, highly politicised activity, concerned with balancing a number of factors including evidence, personal experience, concern for smokers, and the desire for public support for policy. The majority of participants were cautious about making substantive policy moves on smokefree places because of their perception of the issue as highly controversial, their wish to avoid public resistance and their desire for community engagement. Preference was shown for a policy approach based on persuasion rather than legislation, as a means to make progress on smokefree cars and outdoor spaces. The results indicate the need for good communication of the acceptability and benefits of legislative smokefree changes to both the political and public arena.


Cytokines in the pathophysiology and treatment of chronic B-cell malignancies. A review.
Chronic B-cell malignancies are characterized by accumulation of transformed B cells of low proliferative index in lymphatic and extralymphatic tissues. Cytokines do not appear to play a role in the primary step of transformation. However, proliferation as well as inhibition of apoptosis of malignant B cells can readily be explained by cytokine effects. Clinical trials of interferons (IFN) and interleukin-2 alone or in combination have been performed in patients with hairy cell leukemia (HCL), CLL, and low- and intermediate-grade non-Hodgkin's lymphoma. While IFN alpha became standard therapy of HCL, responses in other entities were variable, ranging from 0 to 70% in selected populations. Combination of IFN and cytotoxic chemotherapy in general revealed no additional benefit as compared to chemotherapy alone. Perspectives for future clinical testing of cytokines in low-grade B-cell lymphomas are discussed.


A nucleic acid-based medication for allergic skin diseases.
Among allergic skin diseases, atopic dermatitis is the most difficult to cure. In the majority of patients, atopic dermatitis can be easily controlled by treatment based on three therapeutic approaches: avoidance of precipitating factors, skin care, and medication. In some adult patients, however, severe atopic dermatitis is refractory to treatment, and no fundamental effective treatment modality has yet been established for such cases. Chronic contact dermatitis without an identified causative hapten is also considered an allergic skin disease that is difficult to cure. Topical nucleic acid-based medications are currently being applied clinically, and an ointment containing nuclear factor-κB decoy oligodeoxynucleotides (hereafter referred to as Decoy) has reached clinical trials. In addition, synthetic double-stranded DNA with high affinity for signal transducers and activators of transcription 6 (STAT6) introduced in vivo as a decoy cis element to bind the transcriptional factor and block the activated gene that contributes to the onset and progression of atopic dermatitis functions as an effective therapeutic agent. We also introduce another STAT1 decoy treatment, cytosine-phosphate-guanine-ODN or STAT6 small interfering RNA therapy, for allergic skin diseases.


Dose-response relationship for chromosome aberrations induced by fecapentaene-12 in human lymphocytes.
Chromosome analyses were carried out in human lymphocytes exposed to a synthetic racemic all-trans fecapentaene-12 at 2-24 microM. A dose-dependent increase of the incidences of chromatid-type changes with distinct saturation at higher doses could be observed. The results reveal for the first time that fec-12 is a potent direct-acting mutagen in human lymphocytes.


A comparison of two noninvasive methods in the determination of the anaerobic threshold in children.
Seventy children, ranging in age from 7 to 14 years, performed a maximal exercise test on a treadmill with determination of the anaerobic threshold (AT) by two methods: (1) with the gas exchange method the ventilatory anaerobic threshold (VAT) was identified by the increase in the ventilatory equivalent for O2 uptake without a concomitant increase in the ventilatory equivalent for CO2 output and (2) with the method proposed by Conconi, the AT was taken at the point beyond which the increase in work intensity exceeded the increase in heart rate and the linearity of the work rate/heart rate relationship was lost. The AT values measured with the two methods were correlated (r = 0.80, P less than 0.001). This result confirms, also in children, the validity of the simple Conconi method: It can be used particularly for the determination of the individual optimal intensity of training.


The bioeconomy in Italy and the new national strategy for a more competitive and sustainable country.
Italy has the third largest bioeconomy in Europe (€330 billion annual turnover, 2 million employees), making it a core pillar of the national economy. Its sectors of excellence are food and biobased products, and it is a consistent presence in research and innovation projects funded by the EU Horizon 2020 programme (Societal Challenges 2) and the European Public Private Partnership "Biobased industry" (BBI-JU). The bioeconomy reduces dependence on fossil fuels and finite materials, loss of biodiversity and changing land use. It contributes to environmental regeneration, spurs economic growth and supports jobs in rural, coastal and abandoned industrial areas, leveraging local contexts and traditions. In 2017 the Italian government promoted the development of a national Bioeconomy Strategy (BIT), recently updated (BIT II) to interconnect more efficiently the pillars of the national bioeconomy: production of renewable biological resources, their conversion into valuable food/feed, biobased products and bio-energy, and transformation and valorization of bio-waste streams. BIT II aims to improve coordination between Ministries and Italian regions in alignment of policies, regulations, R&I funding programmes and infrastructures investment. The goal is a 15 % increase in turnover and employment in the Italian bioeconomy by 2030. Based on Italy's strategic geopolitical position in the Mediterranean basin, BIT II also includes actions to improve sustainable productivity, social cohesion and political stability through the implementation of bioeconomy strategies in this area. This paper provides an insight into these strategies and discusses the strengths and weaknesses of the sectors involved and the measures, regulatory initiatives and monitoring actions undertaken.


Feeding OTA to pigs: Analytical evaluation of a trial.
Methods were developed to analyse the concentrations of ochratoxin A (OTA) and its main metabolite ochratoxin α in blood plasma of pigs and in their kidneys. By the use of these methods blood and kidneys of pigs that were fed contaminated feedstuff containing 1500 μg/kg ochratoxin A for the whole trial period of 42 days were analysed.High levels of 1500 - 2000 μg/I OTA were found in the plasma, while the concentration of OTA in the kidneys did not exceed 250 μg/kg at the end of the trial. Neither in the plasma nor in the kidneys of the animals fed contaminated feedstuff ochratoxin a could be detected.


High dose and compartmental target volume may improve patient outcome after radiotherapy for pelvic bone metastases from hepatocellular carcinoma.
Pelvic bone metastases are difficult to treat because of complex pelvic bone anatomy and the proximity of normal organs. The adequacy of radiation dose and field coverage was evaluated. We analyzed 146 cases of pelvic bone metastases from HCC treated with radiotherapy (RT). Bone metastases were confirmed using CT/MRI. Subjective pain response was assessed using the visual analogue scale, and treatment-related toxicity with the Common Terminology Criteria for Adverse Events v3.0. Local failure free survival (LFFS) and overall survival were estimated using the Kaplan-Meier method. The local control rate was 80.1% and the pain control rate was 68.5%. Compartmental target volume (CTV), encompassing the whole compartment of the involved bone, was found to be a significant factor (1-year LFFS, 78% vs. 50%; p=0.001). Sites of metastasis were categorized as either upper or lower pelvic bone; both categories showed improved local control with CTV. Metastatic lesions that received more than 50 Gy of EQD2 showed more partial response in pain after RT (58% vs. 79%; p=0.007). No patient showed toxicity higher than Grade IV. Compartmental RT targeted to the involved bone was associated with improved local control and LFFS. High-dose radiation was associated with an improved treatment response.


Reduced tumour cell proliferation and delayed development of high-grade mammary carcinomas in cathepsin B-deficient mice.
Expression levels of the papain-like cysteine protease cathepsin B (Ctsb) have been positively correlated with mammary tumour progression and metastasis; however, its roles in the hallmark processes of malignant growth remain poorly defined. Using Ctsb-deficient mice we investigated tumour cell differentiation, proliferation and apoptosis in the Tg(MMTV-PyMT) mouse mammary cancer model. Absence of Ctsb significantly impaired development of high-grade invasive ductal carcinomas and reduced the metastatic burden in the lungs. Mice lacking Ctsb exhibited reduced cell proliferation in mammary carcinomas and their lung metastases. Notably, intravenous injection of primarily isolated, Ctsb-expressing tumour cells into congenic Ctsb-deficient mice revealed impaired cell proliferation in the resulting experimental lung metastases, providing evidence for the involvement of Ctsb in paracrine regulation of cancer cell proliferation. No Ctsb genotype-dependent difference in tumour cell death was observed in vivo or by treatment of isolated PyMT cancer cells with tumour necrosis factor-alpha. However, cancer cells lacking Ctsb exhibited significantly higher resistance to apoptosis induction by the lysosomotropic agent Leu-Leu-OMe. Thus, our results indicate an in vivo role for Ctsb in promoting cellular anaplasia in mammary cancers and proliferation in lung metastases.


Widening ethnic inequities in heart failure incidence in New Zealand.
Ethnic inequities in heart failure (HF) have been documented in several countries. This study describes New Zealand (NZ) trends in incident HF hospitalisation by ethnicity between 2006 and 2018. Incident HF hospitalisations in ≥20-year-old subjects were identified through International Classification of Diseases, 10th Revision-coded national hospitalisation records. Incidence was calculated for different ethnic, sex and age groups and were age standardised. Trends were estimated with joinpoint regression. Of 116 113 incident HF hospitalisations, 12.8% were Māori, 5.7% Pacific people, 3.0% Asians and 78.6% Europeans/others. 64% of Māori and Pacific patients were aged <70 years, compared with 37% of Asian and 19% of European/others. In 2018, incidence rate ratios compared with European/others were 6.0 (95% CI 4.9 to 7.3), 7.5 (95% CI 6.0 to 9.4) and 0.5 (95% CI 0.3 to 0.8) for Māori, Pacific people and Asians aged 20-49 years; 3.7 (95% CI 3.4 to 4.0), 3.6 (95% CI 3.2 to 4.1) and 0.5 (95% CI 0.4 to 0.6) for Māori, Pacific people and Asians aged 50-69 years; and 1.5 (95% CI 1.4 to 1.6), 1.5 (95% CI 1.3 to 1.7) and 0.5 (95% CI 0.5 to 0.6) for Māori, Pacific people and Asians aged ≥70 years. Between 2006 and 2018, ethnicity-specific rates diverged in ≥70-year-old subjects due to a decline in European/others (annual percentage change (APC) -2.0%, 95% CI -2.5% to -1.6%) and Asians (APC -3.3%, 95% CI -4.4% to -2.1%), but rates remained unchanged for Māori and Pacific people. In contrast, regardless of ethnicity, rates either increased or remained unchanged in <70-year-old subjects. Ethnic inequities in incident HF hospitalisation have widened in NZ over the past 13 years. Urgent action is required to address the predisposing factors that lead to development of HF in Maori and Pacific people.


The evaluation of effect of alpha-lipoic acid and vitamin E on the lipid peroxidation, gamma-amino butyric acid and serotonin level in the brain of mice (Mus musculus) acutely intoxicated with lindane.
The objective of the present study was to evaluate the neurotoxic effects of lindane, in mice and the protective potential of two antioxidants alpha-lipoic acid (ALA) and vitamin E, against the observed lindane induced toxicity. 7-8 weeks old healthy Swiss mice were administered acute doses of lindane (40 mg/kg b.w.) or antioxidants or both subcutaneously and analyzed 18 h later. ALA and vitamin E were used in the combination for neuroprotection in the concentration of 20 mg/kg b.w. and 50 mg/kg b.w. respectively. Lipid peroxidation, gamma-amino butyric acid (GABA) and serotonin level were used as biochemical test of toxic action for lindane induced acute toxicity. Protective effects of ALA and vitamin E were also evaluated on the same parameters. Reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) level served as an index for determining the extent of lipid peroxidation. Treatment of lindane to normal control animals resulted in a significant decrease and increase in GSH (P<0.01) and TBARS level (P<0.01) respectively in crude homogenate of whole brain. Antioxidants treatment significantly altered the level of GSH (P<0.01) and TBARS (P<0.01). GABA and serotonin level in whole brain as well as in different regions of brain were measured. Main brain regions under the investigation were olfactory lobe, cerebrum, hippocampus-hypothalamus, cerebellum and pons-medulla. Critical difference (CD) of GABA level in various groups was found significant at 1% in cerebrum and hippocampus-hypothalamus, at 5% in whole brain, cerebellum and pons-medulla (i.e. P<0.01 and P<0.05 respectively). Change in serotonin level in whole brain as well as in all studied brain regions of various groups was found significant at 1% CD (i.e. P<0.01).


Foot loading with an ankle-foot orthosis: the accuracy of an integrated physical strain trainer.
To investigate the value of a built-in physical strain trainer for the monitoring of partial weight bearing with an ankle-foot orthosis. 12 healthy volunteers were asked to perform three trials. Plantar peak pressure values from normal gait (trial one) were defined as 100% (baseline). The following trials were performed with the Vacoped® dynamic vacuum ankle orthosis worn in a neutral position with full weight bearing (trial two) and a restriction to 10% body weight (BW) (trial three), as monitored with an integrated physical strain trainer. Peak plantar pressure values were obtained using the pedar® X system. Peak pressure values were statistically significantly reduced wearing the Vacoped® shoe with full weight bearing for the hindfoot to 68% of the baseline (normal gait) and for the midfoot and forefoot to 83% and 60%, respectively. Limited weight bearing with 10% BW as controlled by physical strain trainer further reduced plantar peak pressure values for the hindfoot to 19%, for the midfoot to 43% of the baseline and the forefoot to 22% of the baseline. The Vacoped® vacuum ankle orthosis significantly reduces plantar peak pressure. The integrated physical strain trainer seems unsuitable to monitor a limitation to 10% BW adequately for the total foot. The concept of controlling partial weight bearing with the hindfoot-addressing device within the orthosis seems debatable but may be useful when the hindfoot in particular must be off-loaded.


[Changes in the brain of persons who participated in the cleaning-up of the Chernobyl AES accident based on the data of radiodiagnosis (single-photon emission-computed radionuclide tomography, x-ray computed tomography and magnetic resonance tomography)].
Presents the data of x-ray examinations of the brain in cleaner-ups of the consequences of the Chernobyl power plant accident who complained of headaches, ache in the bones, poor memory, giddiness, weakness, a drastic drop of performance ability, fits with loss of consciousness. Hypometabolic foci localized both in the white and gray matter of the brain were revealed. X-Ray computer-aided tomography and magnetic imaging showed dilatation of the ventricular system of the brain, dilatation of the subarachnoidal spaces, symmetrical reduction of the density of medullary tissue round the bodies and anterior and posterior horns of lateral ventricles, round the third ventricle, near semi-oval centers, as well as solitary or multiple focal reduction of medullary tissue density. Findings of x-ray methods of diagnosis permit a conclusion on a complex organic involvement of the brain in subjects who participated in liquidation of the consequences of the Chernobyl power plant accident. The most typical are signs of the hypertensive hydrocephalic syndrome with cerebrospinal fluid disturbances and of the vascular encephalic syndrome with development of focal postischemic malacia of the brain matter.


Serum magnesium and potassium levels in hypertensive patients after a therapeutic switch from hydrochlorothiazide plus a potassium supplement to maxzide.
Determinations of serum magnesium and potassium levels and blood pressure were made in 40 hypertensive patients in whom daily therapy with 50 mg of hydrochlorothiazide plus potassium supplements was switched to a once-daily regimen of 50 mg of hydrochlorothiazide plus 75 mg of triamterene (Maxzide). Patients showed no clinically significant changes in blood pressure or in serum magnesium or serum potassium values following the switch. It is concluded that therapy in patients receiving hydrochlorothiazide and up to 60 meq of potassium can be safely switched to Maxzide without adversely affecting serum magnesium levels, serum potassium levels, or blood pressure control.


Removal of methylene blue from wastewater using fly ash as an adsorbent by hydrocyclone.
The excessive release of color into the environment is a major concern worldwide. Adsorption process is among the most effective techniques for color removal from wastewater and fly ash has been widely used as an adsorbent. Therefore, this study was carried out to understand the adsorption behavior of methylene blue from aqueous systems onto fly ash using the continuous mode. Continuous mode sorption experiments were carried out to remove methylene blue from its aqueous solutions in hydrocyclone equipment. The experiments were performed at constant temperature and dimensions of hydrocyclone with variation of flows through the equipment, concentrations of methylene blue solutions and fly ash concentration, respectively. A maximum removal of 58.24% was observed at adsorbent dosage of 900 mg/l at pH 6.75 for an initial methylene blue concentration of 65 mg/l.


Uneven distribution of mitochondrial DNA mutation in MERRF dizygotic twins.
A new family of myoclonic epilepsy with ragged-red fibers (MERRF) was studied at clinical, histological, biochemical and molecular genetic levels. There was a remarkable variation in the age of onset, the clinical presentation and the severity of symptoms. Multiple defects affecting respiratory chain complexes I, III and IV were detected in 2 patients. The point mutation at 8344 of the mitochondrial genome was found in all the maternal lineage with a relatively narrow range of variation in the percentage of mutant mitochondrial genomes. The one exception was represented by a set of dizygotic twins, one clinically affected and showing high proportions of mutant mitochondrial DNAs (mtDNAs) in blood cells, while the other was asymptomatic and showed very small amounts of mutant mt-DNAs in blood and skin. This could suggest an early segregation of the mitochondrial genome during ovogenesis.


Steady-state solutions of split beams in electron storage rings.
Recently, a novel operation method for synchrotron light sources with transversely split beams has been explored to fulfill the rising demand for flexible and high-throughput X-ray sources required in such diverse fields as time-resolved X-ray spectroscopy, molecular chemistry in organic cells, high-resolution medical imaging, quantum materials science or sustainable energy research. Within that novel operation mode, additional stable regions are produced in the horizontal phase space by operating an electron storage ring on a resonance that is driven by the nonlinear sextupole or octupole magnets. In the longitudinal phase space, a similar split can be produced by introducing an oscillation of the synchrotron phase via a modulation of the phase of the radiofrequency resonator. Strong radiation damping in electron storage rings, however, has to be overcome before additional regions in phase space can become populated by particles and form stable islands. This damping mechanism changes the dynamics of the system and causes diffusion between the different islands in phase space, raising the question what kind of equilibrium state exists in the asymptotic temporal limit. In this paper, a finite-differences approximation in rotating action-angle coordinates is used to solve the Vlasov-Fokker-Planck equation and to study the obtained equilibrium states for the longitudinal as well as the transverse case. The number of solution vectors and the magnitude of the corresponding singular values of the matrix of the underlying finite-differences equation are used as abstract indicators to define the required parameter set that provides stable additional beamlets. As a consequence, the beamlets have a stability that is close to that of the main beam in terms of diffusion caused by the radiation damping and quantum excitation.


Temporal Derivative Distribution Repair (TDDR): A motion correction method for fNIRS.
Functional near-infrared spectroscopy (fNIRS) is an optical neuroimaging technique of growing interest as a tool for investigation of cortical activity. Due to the on-head placement of optodes, artifacts arising from head motion are relatively less severe than for functional magnetic resonance imaging (fMRI). However, it is still necessary to remove motion artifacts. We present a novel motion correction procedure based on robust regression, which effectively removes baseline shift and spike artifacts without the need for any user-supplied parameters. Our simulations show that this method yields better activation detection performance than 5 other current motion correction methods. In our empirical validation on a working memory task in a sample of children 7-15 years, our method produced stronger and more extensive activation than any of the other methods tested. The new motion correction method enhances the viability of fNIRS as a functional neuroimaging modality for use in populations not amenable to fMRI.


Morphine reverses the inhibitory effects of repeated saline injections on peritoneal inflammation in mice.
Morphine sc injections reversed the inhibitory effects of daily sc saline injections on the thioglycollate-elicited peritoneal inflammation in Swiss mice.


Vasoactive mediators in pregnancy-induced hypertensive disorders: a longitudinal study.
The objective of this study was to evaluate the extent to which endothelin and the eicosanoids prostacyclin and thromboxane A2 are involved in the pathophysiology of gestational hypertension and preeclampsia. In a longitudinal design, venous blood samples and 24-hour urine specimens were collected from 396 women in each trimester of pregnancy. After delivery of all patients, venous plasma endothelin was assessed in 20 subjects with identified preeclampsia, 48 subjects with gestational hypertension, and 59 normotensive subjects. Urinary excretions of the thromboxane A2 and of the prostacyclin metabolites thromboxane B2 and 6-keto-prostaglandin F1 alpha were assessed in 16 subjects with preeclampsia, 35 subjects with gestational hypertension, and 31 normotensive subjects. Endothelin levels showed a second-trimester drop in all groups. In all 3 gestational trimesters a high correlation was found between the excretion of thromboxane B2 and that of 6-keto-prostaglandin F1 alpha (P <.001). The overall thromboxane B2 and 6-keto-prostaglandin F1 alpha urinary excretions increased throughout pregnancy and the overall thromboxane B2 /6-keto-prostaglandin F1 alpha ratio decreased. No significant differences in endothelin, thromboxane B2, and 6-keto-prostaglandin F1 alpha excretion levels or in thromboxane B2 /6-keto-prostaglandin F1 alpha ratios were found between women with preeclampsia, gestational hypertension, and normotension. Only in a small group of patients with severe preeclampsia (n = 2) and severe gestational hypertension (n = 2) were increased second-trimester endothelin values and increased thromboxane B2 /6-keto-prostaglandin F1 alpha ratios found. In this longitudinal study we found no evidence for prostacyclin deficiency or increased endothelin levels in preeclampsia. Only women with severe preeclampsia and severe gestational hypertension expressed increased endothelin levels and thromboxane dominance over prostacyclin.