Hemodynamic correlates of left ventricular versus right ventricular radionuclide volumetric responses to vasodilator therapy in congestive heart failure secondary to ischemic or dilated cardiomyopathy.
Previous studies have failed to demonstrate the clinical relevance of radionuclide functional measurements during treatment of congestive heart failure (CHF). In the present study, data derived before and during nitroprusside infusion were analyzed in 16 patients with CHF to compare correlations of changes in left (LV) and right ventricular (RV) radionuclide measurements with simultaneous changes in 8 hemodynamic variables. Nitroprusside infusion decreased systemic artery pressure, pulmonary arterial wedge pressure, pulmonary artery pressure, right atrial pressure, and pulmonary and systemic vascular resistance, and increased cardiac output. Nitroprusside decreased LV and RV end-diastolic and end-systolic volumes and increased LV and RV ejection fraction and stroke volume. Changes in RV volumes exceeded changes in LV volumes. LV radionuclide measurements did not correlate significantly with any hemodynamic measurement except for a weak correlation between changes in LV end-systolic volume and right atrial pressure (r = 0.51). In contrast, the combination of changes in RV end-systolic volume and stroke volume predicted changes in pulmonary artery peak systolic (r = 0.90) and mean (r = 0.89) pressures. Changes in pulmonary arterial wedge pressure correlated with changes in RV end-diastolic (r = 0.78) and end-systolic (r = 0.71) volumes. In conclusion, LV radionuclide measurements are of limited value in predicting hemodynamic responses to vasodilator therapy in CHF, whereas RV volumes are strongly influenced by load changes. Their responses to nitroprusside correlate well with changes in pulmonary artery and pulmonary arterial wedge pressures.


The insulin-sensitive glucose transporter, GLUT4, interacts physically with Daxx. Two proteins with capacity to bind Ubc9 and conjugated to SUMO1.
In this study we have used the yeast two-hybrid system to identify proteins that interact with the carboxyl-cytoplasmic domain (residues 464-509) of the insulin-sensitive glucose transporter GLUT4 (C-GLUT4). Using as bait C-GLUT4, we have isolated the carboxyl domain of Daxx (C-Daxx), the adaptor protein associated with the Fas and the type II TGF-beta (TbetaRII) receptors (1,2 ). The two-hybrid interaction between C-GLUT4 and C-Daxx is validated by the ability of in vitro translated C-GLUT4 to interact with in vitro translated full-length Daxx and C-Daxx. C-Daxx does not interact with the C-cytoplasmic domain of GLUT1, the ubiquitous glucose transporter homologous to GLUT4. Replacement of alanine and serine for the dileucine pair (Leu(489)-Leu(490)) critical for targeting GLUT4 from the trans-Golgi network to the perinuclear intracellular store as well as for its surface internalization by endocytosis inhibits 2-fold the interaction of C-GLUT4 with Daxx. Daxx is pulled down with GLUT4 immunoprecipitated from lysates of 3T3-L1 fibroblasts stably transfected with GLUT4 and 3T3-L1 adipocytes expressing physiological levels of the two proteins. Similarly, GLUT4 is recovered with anti-Daxx immunoprecipitates. Using an established cell fractionation procedure we present evidence for the existence of two distinct intracellular Daxx pools in the nucleus and low density microsomes. Confocal immunofluorescence microscopy studies localize Daxx to promyelocytic leukemia nuclear bodies and punctate cytoplasmic structures, often organized in strings and underneath the plasma membrane. Daxx and GLUT4 are SUMOlated as shown by their reaction with an anti-SUMO1 antibody and by the ability of this antibody to pull down Daxx and GLUT4.


Topical mitomycin C therapy for carcinoma in situ of the bladder: a followup.
We studied 15 patients with histologically proved multifocal carcinoma in situ of the bladder who were in remission at a mean followup of 21 months after induction intravesical chemotherapy with mitomycin C. These patients have been followed for a further 28 months, for a total mean duration of 49 months. Of the 15 patients 4 suffered new areas of carcinoma in situ, including 3 who subsequently required cystectomy (2 after unsuccessful intravesical bacillus Calmette-Guerin therapy and 1 with a simultaneous invasive tumor). One patient underwent transurethral resection of the prostate for carcinoma in situ of the prostatic urethra, which subsequently was shown to be limited to mucosa and not involving the deeper ducts nor the stroma. Of the remaining 11 patients 1 died of unrelated disease and 2 suffered recurrent papillary transitional cell carcinoma treated successfully with a combination of intravesical bacillus Calmette-Guerin therapy and resection. The other 8 patients have remained free of tumor. None of the 15 patients had metastatic cancer. We believe that these results support the durability of response after induction mitomycin C therapy. We stress the necessity for prolonged close followup to detect recurrent tumor and to avoid metastatic disease.


Primary renal synovial sarcoma.
Synovial sarcoma of the kidney is a recently reported neoplasm. Only 33 cases have been reported in published studies. It is a difficult neoplasm to differentiate from other renal masses and requires specific molecular/genetic testing. Currently, no treatment guidelines have been established. Accurate diagnosis is imperative to implement effective therapy.


Organophosphonates revealed: new insights into the microbial metabolism of ancient molecules.
Organophosphonates are ancient molecules that contain the chemically stable C-P bond, which is considered a relic of the reducing atmosphere on primitive earth. Synthetic phosphonates now have a wide range of applications in the agricultural, chemical and pharmaceutical industries. However, the existence of C-P compounds as contemporary biogenic molecules was not discovered until 1959, with the identification of 2-aminoethylphosphonic acid in rumen protozoa. Here, we review advances in our understanding of the biochemistry and genetics of microbial phosphonate metabolism, and discuss the role of these compounds and of the organisms engaged in their turnover within the P cycle.


Asymmetrical fatiguing of the gluteus maximus muscles in the elite short-track female skaters.
According to research, fast skating on short distances increases functional asymmetry of leg muscles. As has been proven in many sporting disciplines, this asymmetry can increase the risk of injury. The aim of the study was to analyze the level of right and left myolectrical manifestations of fatigue asymmetry of gluteus maximus muscle in elite skaters on a short track and to compare this phenomenon to a control group. The muscles were chosen deliberately, due to their influence in maintaining the right position during training on ice. The experiment compared a group of eight members of the Polish Women's National Team in short track with a group of eight non-training people. The subjects did the Biering-Sorensen test, in which sEMG (surface electromyography) signal frequency was measured in the gluteus maximus muscles during an isometric contraction. Myolectrical manifestations of fatigue slopes were analyzed with a ANOVA with repeated measures. In the skaters, the myolectrical manifestations of fatigue differed between the right and the left gluteus maximus muscles. All the skaters had higher myolectrical manifestations of fatigue in the right leg. This phenomenon was not observed in the non-training subjects, who on average had similar myolectrical manifestations of fatigue in both legs. Results showed that the right and the left muscles of the skaters in the experimental group differed in myolectrical manifestations of fatigue, but this difference was non-significant in the control group.The subjects from the two groups did not differ in the myolectrical manifestations of fatigue of the left muscle, they did in the myolectrical manifestations of fatigue of the right muscle. The elite speed-track skaters had higher myolectrical manifestations of fatigue in the right muscle than the non-training subjects. Training should thus be planned in a way that minimizes the risk of causing muscle myolectrical manifestations of fatigue asymmetry in skaters despite the typically asymmetrical muscle work during training on ice and competition, thus new training protocols should be developed or considered to decrease that asymmetry. The tests were previously approved by the Bioethical Commission of the Chamber of Physicians in Opole. (Resolution No. 235 of 13 December 2016).


Immunoglobulin Replacement Therapy for Primary Immunodeficiency.
Immunoglobulin replacement therapy has been standard treatment in patients with primary immunodeficiency diseases for the past 3 decades. The goal of therapy is to reduce serious bacterial infections in individuals with antibody function defects. Approximately one-third of patients receiving intravenous immunoglobulin treatment experience adverse reactions. Recent advances in manufacturing processes have resulted in products that are safer and better tolerated. Self-infusion by the subcutaneous route has become popular and resulted in better quality of life. This review summarizes the use of immunoglobulin therapy in primary immunodeficiency diseases including its properties, dosing, adverse effects, and different routes of administration.


Experiences of using clinical pathways in hospitals: Perspectives of quality improvement personnel.
This study aimed to explore the experiences of quality improvement personnel in implementing clinical pathways (CPs) in Korean hospitals. A qualitative study using focus-group interviews was conducted with healthcare professionals in charge of CP development and management in hospitals. Sixteen quality improvement personnel from eight tertiary and seven general hospitals were recruited using purposive sampling. The verbatim transcribed data were analysed using qualitative content analysis. Three key themes emerged: (1) the primary focus of CP development on surgeries through concerted efforts between management and frontline healthcare professionals; (2) CP fidelity management using indicators and feedback to relevant staff or departments; and (3) positive outcomes, despite concerns about system safety. The factors affecting CP use included availability of clinical evidence, flexibility of CPs, top management and clinical leadership, physicians' perceptions of CPs, computerized support systems, and external policies and regulations.


Long-chain fatty acid uptake and FAT/CD36 translocation in heart and skeletal muscle.
Cellular long-chain fatty acid (LCFA) uptake constitutes a process that is not yet fully understood. LCFA uptake likely involves both passive diffusion and protein-mediated transport. Several lines of evidence support the involvement of a number of plasma membrane-associated proteins, including fatty acid translocase (FAT)/CD36, plasma membrane-bound fatty acid binding protein (FABPpm), and fatty acid transport protein (FATP). In heart and skeletal muscle primary attention has been given to unravel the mechanisms by which FAT/CD36 expression and function are regulated. It appears that both insulin and contractions induce the translocation of intracellular stored FAT/CD36 to the plasma membrane to increase cellular LCFA uptake. This review focuses on this novel mechanism of regulation of LCFA uptake in heart and skeletal muscle in health and disease. The distinct signaling pathways underlying insulin-induced and contraction-induced FAT/CD36 translocation will be discussed and a comparison will be made with the well-defined glucose transport system involving the glucose transporter GLUT4. Finally, it is hypothesized that malfunctioning of recycling of these transporters may lead to intracellular triacylglycerol (TAG) accumulation and cellular insulin resistance. Current data indicate a pivotal role for FAT/CD36 in the regulation of LCFA utilization in heart and skeletal muscle under normal conditions as well as during the altered LCFA utilization observed in obesity and insulin resistance. Hence, FAT/CD36 might provide a useful therapeutic target for the prevention or treatment of insulin resistance.


Lifelong vaccination strategy as a tool against pandemics in Hungary
Due to various factors, the chances of infectious disease emergence or re-emergence have increased in the 21st century, thus, the likelihood of new emerging pandemics has also increased. The COVID-19 pandemic, which appeared in 2019, has highlighted that certain new and re-emerging infectious diseases - in the case of lack or delay in effective measures - can spread very rapidly. The main tool for the fight against infectious diseases is immunization through vaccination. While focusing on the personal health, public health, economic and societal benefits of a lifelong immunization strategy, especially in light of the aging society, the goal of this paper is to present the benefits of vaccines. In order to increase the added value of vaccinations it is recommended to create a lifelong immunization strategy.


The toxicities of short-chain primary alcohols and the accumulation of storage bodies in the larval fat body of Drosophila melanogaster.
In terms of the LD50 values for alcohols, third-instar wild-type larvae of Drosophila melanogaster had a greater tolerance to ethanol, n-propanol and n-butanol than alcohol dehydrogenase (ADH)-deficient larvae. The tolerances of the two strains to methanol were similar. Methanol, ethanol, n-propanol and n-butanol all induced higher ADH activity in wild-type larvae. Ethanol, n-propanol, methanol and n-butanol slowed the growth for ADH-deficient larvae, whereas only methanol had this effect on wild-type larvae. The proportion of wild-type pupae to eclose was increased by n-butanol, n-propanol and ethanol. Cytometric methods to measure the densities of storage bodies--glycogen rosettes, protein bodies and lipid droplets--in fat body cells indicated that all of the test alcohols exerted some negative influence on the accumulation of at least one type of storage body. Analyses of total protein, glycogen and acylglycerols indicated that ethanol and n-butanol were associated with an accumulation of acylglycerols in both wild-type and ADH-deficient larvae; whereas, the other test alcohols resulted in low glycogen and protein concentrations in both test strains. The short-chain primary alcohols may in part be toxic to larvae because of disruptions in metabolism that lead to reductions in one or more kinds of storage bodies in the larval fat body.


Pulmonary edema related to changes in colloid osmotic and pulmonary artery wedge pressure in patients after acute myocardial infarction.
Pulmonary artery wedge and plasma colloid osmotic pressures and their relationship to pulmonary edema were investigated in 26 patients with acute myocardial infarction of whom 14 developed pulmonary edema. In the absence of pulmonary edema, both the pulmonary artery wedge pressure and plasma colloid osmotic pressure were in normal range; after onset pulmonary edema, a moderate increase in pulmonary wedge pressure and reduction in plasma colloid osmotic pressure were observed. When the gradient between the plasma colloid osmotic pressure and the pulmonary artery wedge pressure was calculated, highly significant differences were demonstrated (P less than 0.002). In the absence of pulmonary edema, this gradient averaged 9.7 (plus or minus 1.7 SEM) torr; following appearance of pulmonary edema, it was reduced to 1.2 (plus or minus 1.3) torr. During therapy with digoxin and furosemide, reversal of pulmonary edema was closely related to a concomitant change in the colloid osmotic-hydrostatic pressure gradient. These observations indicate that both increases in pulmonary capillary pressure and decreases in colloid osmotic pressure may follow the onset of pulmonary edema. Such decline in colloid osmotic pressure and especially the reduction in colloid osmotic-hydrostatic capillary pressure gradient may favor transudation of fluid into the lungs.


Evidence Is Unclear About the Best Material and Technique Required for Alveolar Ridge Preservation for Dental IMPLANT SITE Development.
Interventions for replacing missing teeth: alveolar ridge preservation techniques for dental implant site development. Atieh MA, Alsabeeha NH, Payne AG, Duncan W, Faggion CM, Esposito M. Cochrane Database Syst Rev 2015. https://doi.org/10.1002/14651858.CD010176.pub2. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Systematic review with meta-analysis.


Vocal cord adduction causing obstructive sleep apnea from vagal nerve stimulation: case report.
A recognized complication of vagal nerve stimulation is new or worsening sleep apnea. Its pathophysiology is not clearly understood. We report a patient with obstructive sleep apnea that was directly associated with vagal nerve stimulation causing recurring vocal cord adduction. Adjusting the stimulator settings resolved the problem.


68 Ga-PSMA-PET for radiation treatment planning in prostate cancer recurrences after surgery: Individualized medicine or new standard in salvage treatment.
68 Ga-PSMA-PET imaging is a novel promising diagnostic tool to locate early biochemical failure after radical prostatectomy (RP) in prostate cancer (PC) patients. Exact knowledge of the relapse location may result in changes of the therapy concept aside from changes to the TNM stage. To gain data for this approach, we evaluated PC patients receiving 68 Ga-PSMA-PET imaging before salvage radiotherapy (RT). In this study, 100 patients with biochemical failure after RP± prior RT who underwent 68 Ga-PSMA PET/CT or PET/MRI were evaluated undergoing salvage RT in our department. We analyzed TNM staging changes due to 68 Ga-PSMA-PET imaging and its influence on RT planning and treatment. Uptake indicative for tumor recurrence in 68 Ga-PSMA-PET was found in 76% of the patients with biochemical recurrent PC. Median PSA level was 1.0 ng/mL (range 0.12-14.7 ng/mL). Of these, 80% showed no morphological correlate in the corresponding CT or MRI. A 43% of all patients experienced a change in TNM stage due to 68 Ga-PSMA-PET imaging. Patients had changes from Tx to rcT+ (28%), 12% from pN0 to rcN1, 1% from pN0/cM0 to rcM1a, and 8% from cM0 to rcM1b. Due to the additional knowledge of 68 Ga-PSMA-PET imaging, initial planned RT planning was adapted in 59% of all cases. An additional simultaneous integrated boost (SIB) to the prostate bed or lymph nodes was given to 32% and 63%, respectively. Ten patients received stereotactic body RT (SBRT) to single bone metastases. 68 Ga-PSMA-PET imaging showed a high clinical impact on staging and RT management in patients with biochemically recurrent PC, even at low serum PSA levels. With 43% changes in staging and 59% in radiotherapy planning 68 Ga-PSMA-PET could lead to an indispensable tool in guiding radiation treatment in recurrent PC.


Thirteen-year nationwide trends in use of implantable cardioverter-defibrillators and subsequent long-term survival.
Long-term trends in use of implantable cardioverter-defibrillators (ICDs) and outcomes are rare. We examined 13-year nationwide trends in ICD implantation and survival rates in Denmark. Using medical databases, we identified all first time ICD recipients in Denmark during 2000-2012 (N = 8460) and ascertained all-cause mortality. We computed standardized annual implantation rates and mortality rate ratios according to age, sex, comorbidity level, indication, and device type. The standardized annual implantation rate increased from 42 per million persons in 2000 to 213 per million persons in 2012 (from 34 to 174 for men and from 8 to 39 for women). The increase was driven by secondary prophylactic ICDs until 2006 and primary prophylactic ICDs thereafter. The increase occurred particularly in older patients and those with a high level of comorbidity. Independent of indication, 76% of all patients with ICD were alive after 5 years. Men had a higher mortality rate compared with women (mortality rate ratio 1.28; 95% confidence interval 1.10-1.49). Compared with low comorbidity level, moderate, severe, and very severe comorbidity levels were associated with 1.6-, 2.5-, and 4.9-fold increased mortality rates, respectively. The most influential individual comorbidities were heart failure, diabetes, liver disease, and renal disease. The annual implantation rate of ICDs increased 5-fold in Denmark between 2000 and 2012. The rate increase occurred for both men and women, but particularly in the elderly and patients with severe comorbidity. Five-year survival probability was high, but severe comorbidity and male sex were associated with shorter survival.


Studies on the inhibitory action of somatostatin in the electrically stimulated rat vas deferens.
Somatostatin (SS) inhibits in a dose-dependent manner electrically evoked contractions in the rat vas deferens. This action was not modified by yohimbine, naloxone or a mixture of antagonists containing atropine, phentolamine, methysergide, burimamide, propranolol and indomethacin, but was markedly potentiated by reducing the Ca2+ concentration of the medium from 2.5 to 1.25 mM and greatly inhibited when increasing the Ca2+ concentration of the medium from 2.5 to 5.0 mM. Clonidine (CLO), but not beta-endorphin (ENDO) was affected similarly to SS by changing the Ca2+ concentration of the medium. The contractile effect of norepinephrine in unstimulated rat vas deferens was not altered by SS. These results were taken as an indication that SS produces its inhibitory action in the rat vas deferens by interacting with specific SS and its receptors presumably located in the cell membranes of adrenergic nerve terminals. The interaction between SS and its receptors may provoke a decreased diffusion of Ca2+ ions into the nerve terminals and/or a decreased mobilisation of Ca2+ ions from intraneuronal stores thus leading to a reduction in electrically evoked release of norepinephrine.


Ultraviolet-absorbing pseudophakos: an efficacy study.
The use of intraocular lenses (IOLs) to replace cataractous lenses has raised question of possible retinal damage due to exposure to ultraviolet (UV) radiation. Three groups of cynomolgus monkeys underwent cataract operations and either received normal UV-transparent IOLS or UV-opaque IOLs, or were left aphakic. All eyes were later exposed to UV light for varying periods of time. Exposure to UV light produced severe retinal lesions. In aphakic eyes and those with normal IOLs lengthy exposure to low levels of UV light produced lesions similar to those seen after brief, very intense UV radiation. Eyes with UV-opaque IOLs displayed no such lesions. Our results indicate that clinicians should consider the use of UV-opaque IOLs.


Characteristics of cytochrome P450-dependent metabolism in the liver of the wild raccoon, Procyon lotor.
Wildlife is exposed to a wide range of xenobiotics in the natural environment. In order to appropriately assess xenobiotic-induced toxicity in wildlife, it is necessary to understand metabolic capacities. Carnivores, in general, have low metabolic abilities, making them vulnerable to a variety of chemicals. Raccoons (Procyon lotor) in the wild have been found to have high levels of xenobiotics. However, little is known about the metabolic capacity of the cytochrome P450 (CYP) enzymes in this species. Thus, this study used liver samples to investigate the characteristics of CYP enzymes in wild raccoons. In 22 wild raccoons, CYP concentrations in hepatic microsomes were examined. To better understand the properties of CYP-dependent metabolism, in vitro metabolic activity studies were performed using ethoxyresorufin, pentoxyresorufin and testosterone as substrates. In addition, three raccoons were fed commercial dog food in the laboratory for one week, and the effects on CYP-dependent metabolism were investigated. In comparison to other mammalian species, raccoons had very low concentrations of CYP in their livers. In an in vitro enzymatic analysis, raccoons' ethoxyresorufin O-deethylase (EROD) and pentoxyresorufin O-depentylase (PROD) metabolic capacities were less than one-fifth and one-tenth of rats', respectively. These results indicate the possible high risk in raccoons if exposed to high levels of environmental xenobiotics because of their poor CYP activity. In this study, the features of CYP-dependent metabolism in wild raccoons are described for the first time.


Major arteriovenous fistula complicating aorto-iliac aneurysms.
Seven cases of fistula developing between aortic or iliac aneurysms and adjacent major venous trunks are presented. The clinical diagnosis and principles of management of this exceptionally rare complication are discussed in the light of the literature on the subject.


Use of antibiotics by urban and rural residents in Heilongjiang Province, China: cross-sectional study.
To identify and compare the factors affecting the knowledge of, attitude towards and use of antibiotics between urban and rural residents in China. A total of 3631 urban and rural residents in Heilongjiang Province, China, were selected using random sampling. Questionnaires recorded demographic characteristics and participant knowledge of, attitude towards and use of antibiotics. The responses of rural and urban residents were compared, and logistic regression analysis was applied to identify the factors that may contribute to the knowledge of, attitude towards and use of antibiotics. The majority of the participants (>60%) were aware that antibiotics could be used to treat bacterial infections and that bacteria could be resistant to antibiotics. However, only roughly half (40-60%) of the participants were aware that bacterial resistance to antibiotics had become a problem in China. Urban participants reported a more adequate knowledge of, attitude towards and use of antibiotics than rural participants. Logistic regression analysis indicated that urban residency, female gender and level of education were associated with knowledge of, attitude towards and use of antibiotics. Within our sample in Heilongjiang Province, the knowledge of, attitude towards and use of antibiotics were suboptimal in roughly half of all urban and rural residents, but better in urban than in rural residents. Targeted interventions to educate rural residents in particular may reduce the misuse of antibiotics.


Modifications to the anaerobic digestion model no. 1 (ADM1) for enhanced understanding and application of the anaerobic treatment processes - A comprehensive review.
Anaerobic digestion (AD) is a promising method for the recovery of resources and energy from organic wastes. Correspondingly, AD modelling has also been developed in recent years. The International Water Association (IWA) Anaerobic Digestion Model No. 1 (ADM1) is currently the most commonly used structured AD model. However, as substrates become more complex and our understanding of the AD mechanism grows, both systematic and specific modifications have been applied to the ADM1. Modified models have provided a diverse range of application besides AD processes, such as fermentation and biogas upgrading processes. This paper reviews research on the modification of the ADM1, with a particular focus on processes, kinetics, stoichiometry and parameters, which are the major elements of the model. The paper begins with a brief introduction to the ADM1, followed by a summary of modifications, including extensions to the model structure, modifications to kinetics (including inhibition functions) and stoichiometry, as well as simplifications to the model. The paper also covers kinetic parameter estimation and validation of the model, as well as practical applications of the model to a variety of scenarios. The review highlights the need for improvements in simulating AD and biogas upgrading processes, as well as the lack of full-scale applications to other substrates besides sludge (such as food waste and agricultural waste). Future research directions are suggested for model development based on detailed understanding of the anaerobic treatment mechanisms, and the need to recover of valuable products.


Association of mannose-binding lectin 2 gene polymorphisms with Guillain-Barré syndrome.
Complement activation plays a critical role in the pathogenesis of Guillain-Barré syndrome (GBS), a debilitating immune-mediated neuropathy. Mannose-binding lectin (MBL) is a complement activation factor of lectin pathway which as genetic host factor may influence the susceptibility or severity of GBS. We investigated the frequency of MBL2 promoter (- 550H/L and - 221X/Y) and functional region (exon 1 A/O) polymorphisms and their association with disease susceptibility, clinical features and serum MBL among GBS patients (n = 300) and healthy controls (n = 300) in Bangladesh. The median patient age was 30 years (IQR: 18-42; males, 68%). MBL2 polymorphisms were not significantly associated with GBS susceptibility compared to healthy controls. HL heterozygosity in GBS patients was significantly associated with mild functional disability at enrolment (P = 0.0145, OR, 95% CI 2.1, 1.17-3.82). The HY, YA, HA and HYA heterozygous haplotypes were more common among mildly affected (P = 0.0067, P = 0.0086, P = 0.0075, P = 0.0032, respectively) than severely affected patients with GBS. Reduced serum MBL was significantly associated with the LL, OO and no HYA variants and GBS disease severity. No significant association was observed between MBL2 polymorphisms and electrophysiological variants, recent Campylobacter jejuni infection or anti-ganglioside (GM1) antibody responses in GBS. In conclusion, MBL2 gene polymorphisms are related to reduced serum MBL and associated with the severity of GBS.


Analysis of severe photoreceptor loss and Morris water-maze performance in aged rats.
In a study of aging and memory in 25-27-month-old albino rats, performance on a Morris water maze was found to be dependent on the structural integrity of the retina. Generally, as expected, 'learners' had intact retinas, while 'non-learners' had retinas with severe photoreceptor loss and a non-continuous outer nuclear layer, consisting of scattered cell nuclei. However, contrary to this general correlation between learning ability and photoreceptor presence, some learners had severely degenerated retinas and occasionally, non-learners had photoreceptor populations that apparently were comparable to those of learners. Rat retinas from these unpredictable, borderline response categories were examined histopathologically and morphometrically with the purpose of determining the minimal number of photoreceptors (PRs) necessary for animals to be rated as learners on the Morris water maze. However, among these severely damaged retinas of borderline groups, total number of surviving photoreceptors did not vary significantly among the learner, ambiguous or marginal and non-learner groups. The population of surviving PRs in learners was as low as 0.04% and in non-learners as high as 0.4%, as compared to that of young, adult rats. Therefore, borderline learners and non-learners had overlapping surviving PR numbers and the results did not clarify the response difference between these groups in the Morris water maze. It is suggested that the pattern of surviving PRs over the retinal surface, as well as the ratio of surviving rods to cones and their connectivity with other retinal neurons, may be related to the residual function of degenerated retinas of learner rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Genetic variants in SCN5A promoter are associated with arrhythmia phenotype severity in patients with heterozygous loss-of-function mutation.
Heterozygous SCN5A mutations have been associated with varied arrhythmia phenotypes; phenotype severity may range from asymptomatic electrocardiographic changes (mild phenotype) to symptomatic arrhythmias resulting in syncope, cardiac arrest, and sudden cardiac death (severe phenotype) even among family members carrying the same mutation. Risk-stratification schemes for SCN5A mutation carriers remain uncertain. To determine the role of SCN5A promoter variants and DNA methylation by using a family-based approach in predicting phenotype severity in a kindred with loss-of-function SCN5A mutation. In a large kindred with a heterozygous SCN5A loss-of-function mutation (1936delC, Q646RfsX5; 22 mutation carriers), we sought SCN5A promoter variants. In addition, we assessed SCN5A and genome-wide DNA methylation profiles on genomic DNA derived from blood (Illumina Human Methylation27 BeadChip). During systematic survey of the 2.8-kb SCN5A promoter region, we identified 2 single nucleotide polymorphisms in complete linkage disequilibrium (rs41310749 and rs41310239). These promoter variants were significantly associated with disease severity (mild vs severe phenotype) (P = .0007), as all 3 patients with severe phenotype carried the 2-SNP variant on both mutant and wild-type alleles. Analysis did not support a role for the methylation of SCN5A-related genes. These family-based genetic findings suggest that the presence of specific promoter variants increase the risk of a severe phenotype in heterozygous carriers of an SCN5A loss-of-function mutation.


Production of an antibiotic by an organism from human feces.
An antibiotic-producing, gram-positive, rod-shaped bacterium was isolated from an individual who often lacked coliforms and fungi in fecal samples. The cell-free antibiotic is 1,200 daltons and Pronase sensitive and was shown to have activity against some coliforms and yeast.


Bioinformatics approaches to quadruplex sequence location.
Guanine quadruplex structures are potentially useful therapeutic targets. There have been several studies attempting to locate genomic sequences which are capable of forming these structures. Since the number of potential quadruplex forming sequences which have been identified is so high, several different strategies have been applied to try and determine which of these sequences may be physiologically relevant and which sequences are most likely to form quadruplex structures. These are based on the limited structural information that is currently available and comparative analyses of the location of these sequences with respect to different genomic regions. Sequence information alone is not enough to identify regions of nucleic acid which participate in quadruplex structures, however it is the starting point for quadruplex structure discovery when complemented with further experimentation.


Parity-associated alterations of medial preoptic opiate receptors in female rats.
Preoptic area opiate receptor density was measured by quantitative autoradiography using [3H]naloxone in female rats during their first and second pregnancies and lactations and in a separate group of ovariectomized, nulliparous animals. Opiate receptor density in the medial preoptic area (MPOA) was elevated on day 12 of gestation in both primigravid and multigravid rats when compared with ovariectomized subjects. MPOA receptor density was reduced in primiparous mothers on day 5 of lactation relative to pregnancy. In contrast, receptor density in the MPOA did not decline in multiparous (second lactation) rats relative to pregnancy levels. Opiate receptor density was significantly higher on day 5 of lactation in multiparous than in primiparous mothers. No difference in receptor density was detected in the adjacent lateral preoptic area among the treatment groups. An examination of hormone titers revealed that basal prolactin levels were significantly higher in primigravid than multigravid rats, and that during lactation prolactin titers were negatively correlated with MPOA opiate receptor density in the primiparous mothers. The data demonstrate that multiple pregnancies and lactations result in changes of MPOA opiate receptor density and of circulating hormone levels. The findings are discussed in terms of the concurrent changes in neural opiate sensitivity associated with multiparity.


Endogenous glucose production after stomach resection.
Endogenous glucose production was measured in eight patients after stomach resection to determine glucose requirement after elective surgery in five patients during infusion of 2.1 - 2.9 g glucose.kg/day (low glucose) and in three patients during infusion of 6.2 - 6.9 g glucose.kg/day (high glucose). Endogenous glucose production was defined as the difference between total glucose turnover measured by 2-3H-glucose and the glucose infusion rate. Endogenous glucose production was the same in both groups, respectively 0.010 +/- 0.002 and 0.009 +/- 0.002 mmol kg/min. It was concluded that a daily quantity of glucose equal to the endogenous production of 180 g. 70 kg/day should be the minimum given after stomach resection.


Age Significantly Affects Response Rate to Outcomes Questionnaires Using Mobile Messaging Software.
To investigate the demographic factors that influence time to respond (TTR), time to completion (TTC), and response rate when using a text messaging-based system and to determine the feasibility and applicability of mobile messaging-based services for collection of patient-reported outcomes among orthopaedic sports medicine patients. On the day of surgery, patient mobile phone number was collected and the automated mobile messaging service (MOSIO, Seattle, WA) messaged patients for 10 ``days postoperatively. Patient visual analog scale (VAS) scores were collected 3 times daily, side effects were asked each evening, and Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference (PI) Short Form was collected on postoperative day 3 and 7. A total of 177 patients were enrolled in the study. The overall response rate to the survey questions was 75.0%. For all patients, the average TTR of questions was 35.09 ± 12.57 minutes. The TTC was 2.75 ± 3.56 minutes for PROMIS-PI, 3.51 ± 1.26 minutes for VAS, and 3.80 ± 6.87 for side-effect questions. When patients were stratified into age groups, the youngest group, 16 to 32 years, had the greatest response rate of 85.2% and patients in the 49 to 59 years group had the lowest response rate of 68.4% and 69.1%, respectively (P < .001). There was no significant difference in the TTR or TTC for VAS, PROMIS-PI, or side-effect questions when patients were stratified by age or sex groups (P > .05). Collectively, all age groups successfully achieved a mean response rate of 75%; however, significantly lower response rates were observed for patients >49 years old. Differences in age and sex did not impact the overall TTR or TTC for VAS, PROMIS-PI, or side-effect questions. Mobile-based applications present as an emerging opportunity to track postoperative outcome scores and reduce clinic survey load. Case series, level of evidence IV.


In-situ biological effects, bioaccumulation, and multi-media distribution of organic contaminants in a shallow lake.
Anthropogenic activity-impacted aquatic environment contains a complex mixture of contaminants, and ecological risk assessment solely based on chemical analysis is insufficient and biological assessment is required. However, traditional assessment heavily relies on laboratory bioassays, which may cause uncertainty due to inevitable laboratory-related artifact. A self-designed in-situ bioassay system was successfully applied to simultaneously evaluate water and sediment toxicity by co-exposure of two native species, Chinese rare minnows (Gobiocypris rarus) and Asian clams (Corbicula fluminea) in Tai Lake Basin, China. In-situ exposure caused pronouncedly lethal and sublethal effects (i.e., metabolic and oxidative stress, neurotoxicity, reproductive toxicity) on both fish and clams. Meanwhile, multi-media distribution of organic contaminants in water-sediment-biota system was analyzed. Besides hydrophobicity, metabolism was recognized as an influential factor on phase distribution of contaminants in water-fish and sediment-clam systems. Traditional hazard quotient (HQ) method based on environmental concentrations of 98 contaminants showed bias in risk assessment. Instead, a weight of evidence method by integrating three lines of evidence, including in-situ survival, enhanced integrated biomarker response values and environmental concentrations, successfully differentiate high- and moderate-risk sites in the shallow lakes. The present study incorporated in-situ bioassays into risk assessment using a weight of evidence approach, which reduced uncertainty in decision-making.


Use of a sedation-analgesia datasheet in closed shoulder reductions.
A three-page conscious sedation (CS) monitoring datasheet and sedation-analgesia policy were implemented at the Lincoln Hospital Emergency Department (LHED) to maintain compliance with JCAHO and New York State standards on CS monitoring. The datasheet included areas for physical examination, medications, and vital signs. To determine effects of the new datasheet and policy, charts containing all closed shoulder reductions done at LHED from April 3, 1996 to June 30, 1999 (n = 237) were reviewed for use of CS, defined as the use of an analgesic and sedative-hypnotic concurrently. Utilization of CS during equal time periods of 591 days before and after datasheet implementation was analyzed and compared. Before use of the datasheet, 64.3% received CS before closed shoulder reduction, compared with 41.8% after its use began (p < 0.05). A subsequent survey was conducted to determine physician perception of the CS datasheet. Attending-level LHED physicians suggested that use of the datasheet increased charting time and liability.


[Microtransplantation of hormone receptors by cell fusion].
Defective hormone receptors are cultivated in cell cultures and subsequently reconstituted by, in-vitro cell fusion technique.


Nod-like receptor pyrin domain containing 3 plays a key role in the development of Th2 cell-mediated host defenses against Trichinella spiralis infection.
The inflammasome is a key line of immune defense against invading infectious pathogens. However, knowledge of the role of nod-like receptor pyrin domain containing 3 (NLRP3) in Trichinella spiralis infection which characteristically induces T-helper 2 (Th2) immune responses is sparse. In this study, we investigated the role of NLRP3 in the protection against T. spiralis infection through the Th2 immune response. We show that NLRP3 expression in CD4+ T cells was significantly increased at 7 days post-infection of T. spiralis. Compared to wild-type (WT) CD4+ T cells, the expression of IL-4 mRNA was reduced in NLRP3-/- CD4+ T cells, however, the expression of IFN-γ mRNA was comparable between the two groups. Consistently, ELISA and flow cytometry analysis showed that NLRP3-/- CD4+ T cells secreted lower levels of IL-4 than CD4+ T cells from WT mice, whilst the levels of IFN-γ secreted by NLRP3-/- CD4+ T cells were of similar levels to those secreted by WT CD4+ T cells. In addition, we observed a significant reduction of IL-4 and IL-13 by ELISA in NLRP3 -/- mice at 1, 2 and 4 weeks post-infection. Furthermore, we found that adult worm survival was substantially prolonged and muscle larvae burden was significantly increased in NLRP3 -/- mice. We further show that NLRP3 promotes the host defense against T. spiralis through its participation in the differentiation of Th2 cells. These findings provide novel insights into parasite expulsion and highlight the importance of NLRP3 in the host defense against T. spiralis.


Effects of dietary microbial feed supplement on production efficacy in lactating dairy cows.
This study evaluated the effects of a microbial feed supplement (MFS; Galaxis, Ascus Biosciences Inc.) comprising 2 native rumen microbes on performance parameters in mid-lactation dairy cows. Forty-six lactating primiparous and multiparous Holstein cows [629 ± 62 kg of body weight, mean ± standard deviation (SD); parity 1.64 ± 0.49; 119 ± 38 days in milk; 45.11 ± 3.81 and 52.73 ± 4.77 kg/d of milk yield for primiparous and multiparous, respectively] were enrolled in a study containing 3 experimental periods (P). During all periods, enrolled cows were fed the same base total mixed ration (TMR) ad libitum once daily. During P1 (7 d), baseline data were obtained for covariate analysis. At the beginning of P2 (60 d), cows were assigned to 1 of 2 dietary treatment groups in a randomized complete block design to balance for milk yield (MY), parity, and days in milk: (1) a control diet (CON; base TMR; n = 23), or (2) a control diet supplemented with 5 g/d of MFS (MFS; n = 23). Sample size was determined based on previous, unpublished results involving this MFS; a 3-kg difference between groups with a SD of 3.5 kg could be detected with sufficient power (0.81) using a total sample size of 46 cows. Treatment was top-dressed and hand-mixed into the top one-third of the TMR. During P3 (7 d), no treatment was administered, and all cows were fed the base TMR. When analyzing all cows in the data set, MFS had little to no effect on performance. However, modeling revealed that the fixed effect of covariate milk production level had a significant effect on the response of MY and ECM, and further investigation of the data revealed that treatment effectiveness in P2 correlated with milk production during P1. Cows were retrospectively categorized into 2 milk production groups (MPG) balanced for parity: MPG1 (i.e., <53 kg/d of ECM during P1; n = 34) or MPG2 (i.e., ≥53 kg/d of ECM during P1; n = 12). Energy-corrected milk was increased by 4.4% in MFS-administered MPG1 cows compared with CON cows during P2. Although there were no significant effects of MFS on production variables for MPG2 cows, MY tended to be decreased by 3.9% in MFS-administered cows compared with CON cows. Further investigation is needed to understand production level response differences and the effect of supplemented native rumen microbes on animal health and productivity.


Effects of body electroacupuncture on plasma leptin concentrations in obese and overweight people in Iran: a randomized controlled trial.
The prevalence of obesity, a major public health problem, is increasing in many countries, including Iran. Leptin, a peptide hormone that is released from adipocytes, is a major factor in appetite regulation. Levels of plasma leptin increase with increased body fat mass (BFM). Research has found acupuncture to be effective both in weight loss and suppression of appetite. Although a few studies have reported the effect of body and ear acupuncture on leptin levels, researchers have performed few studies on the effect of body electroacupuncture in humans. The research team examined the effects of body electroacupuncture and a low-calorie diet on plasma leptin in obese and overweight individuals with an excess (phlegm-dampness or phlegm-heat) or deficiency (spleen/stomach qi deficiency or primary qi deficiency) pattern according to Chinese medicine. The research team randomly assigned participants to one of two groups, intervention or control. This study occurred in the nutritional clinic at Ghaem Hospital in Mashhad, Iran. Participants were individuals (N = 86) between 18 and 65 years of age with body mass indexes (BMI) between 25 and 45 kg/m2. The intervention group (n = 47) received actual electroacupuncture, and the control group (n = 47) received sham acupuncture. Both groups consumed a low-calorie diet for 6 weeks. The research team measured plasma leptin, BFM, body weight (BW), and BMI before and after treatment. For participants in the intervention group with both the excess and the deficiency patterns, the research team found a significant reduction in plasma leptin (24.96%, P = .001) and BFM (8.29%, P = .001). In the control group, the team found a less significant reduction in leptin and BFM. The difference between the two groups was significant for leptin (P = .03) but not for BFM (P = .8). While body electroacupuncture with a low-calorie diet can reduce plasma leptin concentration, the mechanism will require further clarification.


Vessel injury and capillary leak.
To understand the mechanism of pathologic capillary leak in the critically ill patient. Review of normal and altered physiology of the microvasculature. Review of recent literature describing pathogenesis, mediators, and interventions influencing capillary leak and microvascular repair. In vitro and in vivo studies, the latter including animal and human subjects. Capillary leak with resultant edema develops in the critical care setting on the basis of perturbations in Starling's equation, primarily as a result of increased capillary permeability to larger molecules. This process is most likely fueled by inflammatory mediators or mechanical stress. Attempts to prevent or treat this process remain largely unsuccessful; resuscitation is more often symptomatic than therapeutic. Models of microvascular repair focus on discrete injury and may not be applicable to the recovery of capillary damage secondary to a systemic leak Our understanding of capillary leak syndrome remains fragmented and weighted toward specific mediators contributing to the leak. The implications of extensive edema and the mechanism by which it resolves continue to be the subject of speculation rather than study.


Detection of IFN-γ Secretion by T Cells Collected Before and After Successful Treatment of Early Lyme Disease.
Current serodiagnostics for Lyme disease lack sensitivity during early disease, and cannot determine treatment response. We evaluated an assay based on QuantiFERON technology utilizing peptide antigens derived from Borrelia burgdorferi to stimulate interferon-gamma (IFN-γ) release as an alternative to serodiagnosis for the laboratory detection of Lyme disease. Blood was obtained from patients with erythema migrans before (n = 29) and 2 months after (n = 27) antibiotic therapy. IFN-γ release was measured by enzyme-linked immunosorbent assay (ELISA) following overnight stimulation of whole blood with the peptide antigens, and compared to the results of standard serological assays (C6, ELISA, and Western blot). IFN-γ release was observed in pretreatment blood of 20 of 29 (69%) patients with Lyme disease. Following antibiotic treatment, IFN-γ was significantly reduced (P = .0002), and was detectable in only 4 of 20 (20%) initially positive patients. By contrast, anti-C6 antibodies were detected in pretreatment sera from 17 of 29 (59%) subjects, whereas only 5 of 29 (17%) patients had positive Western blot seroreactivity. Antibody responses persisted and expanded following treatment. Our findings suggest that measurement of IFN-γ after incubating blood with Borrelia antigens could be useful in the laboratory diagnosis of early Lyme disease. Also, after antibiotic treatment, this response appears to be short lived.


The serological relationship between Theileria parva (Muguga) and Theileria lawrence from Rhodesia.
Thirty-eight sera from cattle from a herd in Rhodesia naturally infected with Theileria lawrencei were titrated with the indirect immunofluorescent test against schizont antigens of T parva (Muguga) and T lawrencei from Rhodesia. T lawrencei was found to be indistinguishable from T parva with the test.


SQSTM1 is a therapeutic target for infection and sterile inflammation.
Inflammation represents a fundamental immune response triggered by various detrimental stimuli, such as infections, tissue damage, toxins, and foreign substances. Protein degradation plays a crucial role in regulating the inflammatory process at multiple levels. The identification of sequestosome 1 (SQSTM1, also known as p62) protein as a binding partner of lymphocyte-specific protein tyrosine kinase in 1995 marked a significant milestone. Subsequent investigations unveiled the activity of SQSTM1 to interact with diverse unstructured substrates, including proteins, organelles, and pathogens, facilitating their delivery to the lysosome for autophagic degradation. In addition to its well-established intracellular functions, emerging studies have reported the active secretion or passive release of SQSTM1 by immune or non-immune cells, orchestrating the inflammatory responses. These distinct characteristics render SQSTM1 a critical therapeutic target in numerous human diseases, including infectious diseases, rheumatoid arthritis, inflammatory bowel disease, pancreatitis, asthma, chronic obstructive pulmonary disease, and cardiovascular diseases. This review provides a comprehensive overview of the structure and modulation of SQSTM1, discusses its intracellular and extracellular roles in inflammation, and highlights its significance in inflammation-related diseases. Future investigations focusing on elucidating the precise localization, structure, post-translational modifications of SQSTM1, as well as the identification of additional interacting partners, hold promise for unravelling further insights into the multifaceted functions of SQSTM1.


National compliance with UK wide guidelines for usage of valproate in women of childbearing potential.
Valproate (VPA) is an effective treatment for epilepsy and also used in bipolar disorder. However, VPA is associated with a significant risk of birth defects and developmental disorders if used during pregnancy. This has led to the introduction of measures to reduce the use of valproate in women of childbearing potential such as the 'Prevent' pregnancy prevention program (PPP) and the completion of an annual risk acknowledgement form (ARAF). The aim of the current audit was to assess compliance with the guidance. An audit tool was made available to neurologists registered with the Association of British Neurologists (ABN) and to epilepsy nurse specialists via the Epilepsy Nurses Association (ESNA) in the UK. Data were collected between November 2020 and March 2021. The main indication for valproate was generalised epilepsy (55.8%), followed by focal (22.5%). For most, there was documentation that the woman had been informed about the risks associated with taking valproate during pregnancy (93.1%) and the need to be on highly effective contraception or that this was not deemed appropriate (92.2%). A signed ARAF was available in the notes for 81.2% although only 66% were <12 months old. Although information had been made available for most women, there were still individuals where this was not documented. Further work is needed to facilitate identification of women taking valproate and implementation of a digital ARAF. For clinicians, the audit highlights a need to carefully counsel women about the teratogenic risks of continuing to take valproate versus the risk of deteriorating seizure control if the drug is withdrawn. This is particularly true of women with focal epilepsy, where there may be safer, equally effective, alternative anti-seizure medication (ASM). The aim should be to create a partnership of trust between the patient and clinician in order to arrive at the best clinical decision for that individual.


RNA-binding activity and regulatory functions of the emerging sRNA-binding protein ProQ.
Regulatory small RNAs (sRNAs) ubiquitously impact bacterial physiology through antisense-mediated control of mRNA translation and stability. In Gram negative bacteria, sRNAs often associate with RNA-binding proteins (RBPs), both to gain cellular stability and to enable regulatory efficiency. The Hfq and CsrA proteins were for long the only known global RBPs implicated in sRNA biology. During the last five years, the FinO domain-containing protein ProQ has emerged as another global RBP with a broad spectrum of sRNA and mRNA ligands. This review provides a summary of the current knowledge of enterobacterial ProQ, with a special focus on RNA binding activity, RNA ligand preferences, influence on RNA stability and gene expression, and impact on bacterial physiology. Considering that characterization of ProQ is still in its infancy, we highlight aspects that, when addressed, will provide important clues to the physiological functions and regulatory mechanisms of this globally acting RBP.


Tamoxifen cytotoxicity in hepatoblastoma cells stably transfected with human CYP3A4.
Tamoxifen can exert its effects through the competitive inhibition of estrogen receptors or other mechanisms. HepG2 cells lacking estrogen receptors and engineered to overexpress CYP3A4, the most important CYP to metabolize the drug, appear to be a good model to study the effects of tamoxifen metabolites. Tamoxifen altered cell cycle of transduced HepG2 cells, decreased G0/G1 cell numbers, diminished proliferation index and induced cell death mostly in cells overexpressing CYP3A4 but was without significant effect on cytotoxicity or proliferation of cells engineered to overexpress CYP2E1 or on empty vector transfected cells. Tamoxifen did not change MDR1 levels irrespectively on CYP450s expression, but inhibited by approximately 50% p-gp functions in all cell types. Drug treatment significantly increased dehydroepiandrosterone sulfotransferase activity and sulfotransferase inhibition significantly decreased tamoxifen cytotoxicity. Our results support the view that metabolic activation of tamoxifen in liver cells may proceed via CYP450-mediated metabolism and subsequent sulfotransferase-mediated activation and point to the role of CYP3A4 and dehydroepiandrosterone sulfotransferase in adverse tamoxifen effects.


Long noncoding RNAs in lipid metabolism: literature review and conservation analysis across species.
Lipids are important for the cell and organism life since they are major components of membranes, energy reserves and are also signal molecules. The main organs for the energy synthesis and storage are the liver and adipose tissue, both in humans and in more distant species such as chicken. Long noncoding RNAs (lncRNAs) are known to be involved in many biological processes including lipid metabolism. In this context, this paper provides the most exhaustive list of lncRNAs involved in lipid metabolism with 60 genes identified after an in-depth analysis of the bibliography, while all "review" type articles list a total of 27 genes. These 60 lncRNAs are mainly described in human or mice and only a few of them have a precise described mode-of-action. Because these genes are still named in a non-standard way making such a study tedious, we propose a standard name for this list according to the rules dictated by the HUGO consortium. Moreover, we identified about 10% of lncRNAs which are conserved between mammals and chicken and 2% between mammals and fishes. Finally, we demonstrated that two lncRNA were wrongly considered as lncRNAs in the literature since they are 3' extensions of the closest coding gene. Such a lncRNAs catalogue can participate to the understanding of the lipid metabolism regulators; it can be useful to better understand the genetic regulation of some human diseases (obesity, hepatic steatosis) or traits of economic interest in livestock species (meat quality, carcass composition). We have no doubt that this first set will be rapidly enriched in coming years.


Effects of corticosteroids on oxidative damage and circulating carotenoids in captive adult kestrels (Falco tinnunculus).
Birds control body homeostasis through the secretion of corticosterone. This hormone is the end-product of the hypothalamic-pituitary-adrenal (HPA) axis response to stressors. High levels of corticosterone may be associated with low individual fitness and may affect balance between pro-oxidants and antioxidants. Given these points, chronic stress modulated by hormones could undermine individual fitness by increasing oxidative tissue damage. In this study, we administered corticosteroids by diet (20 mg/kg of diet) to captive adult kestrels (Falco tinnunculus) over a 14-day period to evaluate the effects of a simulated chronic stress modulated by corticosteroids. We found that dietary administration of corticosterone caused a 32% increase of reactive oxygen metabolites, but did not impair total serum antioxidant capacity, serum carotenoids or body mass. Oxidative stress had a 64% increase in treated birds compared to 30% in controls. The two groups did not differ in the total serum antioxidant capacity, which showed a significant decrease over the study period. In contrast, circulating carotenoids and body mass increased in both groups. These results suggest that stress hormones, such as corticosterone, may also act as modulators of oxidative stress in birds.


Locus of control at age 10 years and health outcomes and behaviors at age 30 years: the 1970 British Cohort Study.
To examine the relationship between locus of control at age 10 years and self-reported health outcomes (overweight, obesity, psychological distress, health, and hypertension) and health behaviors (smoking and physical activity) at age 30, controlling for sex, childhood IQ, educational attainment, earnings, and socioeconomic position. Participants were members of the 1970 British Cohort Study, a national birth cohort. At age 10, 11,563 children took tests to measure locus of control and IQ. At age 30, 7551 men and women (65%) were interviewed about their health and completed a questionnaire about psychiatric morbidity. Men and women with a more internal locus of control score in childhood had a reduced risk of obesity (odds ratio, 95% CI, for a SD increase in locus of control, 0.86, 0.78-0.95), overweight (0.87, 0.82-0.93), fair or poor self-rated health (0.89, 0.81-0.97), and psychological distress (0.86, 0.76-0.95). Women with a more internal locus of control had a reduced risk of high blood pressure (0.84, 0.76-0.92). Associations between childhood IQ and risk of obesity and overweight were weakened by adjustment for internal locus of control. Having a stronger sense of control over one's own life in childhood seems to be a protective factor for some aspects of health in adult life. Sense of control provides predictive power beyond contemporaneously assessed IQ and may partially mediate the association between higher IQ in childhood and later risk of obesity and overweight.


A method to cope with the random errors of observed accident rates in regression analysis.
The paper is concerned with linear multiregression analysis on accident rates related to road geometric design elements. Supposing that a data set of accident records and geometric design elements of a certain stretch of a road is given, there are two steps for regression analysis: first, division of the road into a number of segments; and second, application of regression analysis to the set of segments. The main interest of the present paper is the first step. Occurrence of a traffic accident in a road segment is a stochastic event and an observed accident rate in a segment contains a certain magnitude of random error that deteriorates the explanatory power and reliability of the regression analysis. Random errors are required to be appropriately controlled for an effective regression analysis. The first part of the paper discusses how to evaluate a random error contained in an accident rate of a road segment and shows that a random error depends on the number of accidents and vehicle-kilometerage of the segment. It is then shown that random errors of the segment should be as much as possible equal to each other and small enough compared with the accident rate variance based on the discussion of how the random errors affect the efficiency of regression analysis. Several alternative criteria on the random errors for dividing a road into segments are proposed and numerical examples of Tokyo-Kobe Expressway are presented to examine the appropriateness of the alternative criteria. One of them is finally recommended as the most practically useful criterion.


Putting mind and body back together: a human-systems approach to the integration of the physical and cognitive dimensions of task design and operations.
As human factors and ergonomics professionals we should be considering the total context within which the person must operate when performing a task, providing a service, or using a product. We have traditionally thought of the person as having a cognitive system and a physical system and much of our scientific literature has been myopically focused on one or the other of these systems while, in general, totally ignoring the other. However, contemporary efforts have begun to recognize the rich interactions occurring between these systems that can have a profound influence on performance and dictate overall system output. In addition, modern efforts are beginning to appreciate the many interactions between the various elements of the environment that can influence the components of the human systems. The next level of sophistication in the practice of human factors and ergonomics must begin to consider the totality of the human-system behavior and performance and must consider systems design interactions which result from these collective effects. Only then will we be able to truly optimize systems for human use.


Preoperative assessment of the individual anatomy of the superior petrosal vein complex using balanced fast field echo magnetic resonance imaging.
Here, we sought to examine the validity and reproducibility of balanced fast field echo (bFFE) for assessing superior petrosal vein (SPV) complex (SPVC) anatomy. Preoperative bFFE or equivalent scans and operative videos were studied and directly compared with regard to the individual anatomical features of SPVCs and their relation to the operative field. The anatomical details of the bFFE findings of the non-operated side (group 2) of all 50 patients were then reviewed, including the presence of petrosal-galenic anastomosis, and finally compared to the operated SPVCs (group 1). A complete correlation between bFFE and intraoperative findings was observed in 62% of cases and had a significant correlation with 3 Tesla magnet strength and higher pixel bandwidth (rbis = - 0.47; p = 0.005). The sensitivity and specificity of bFFE magnetic resonance imaging were 93.7 and 95.2%, respectively, for detecting an SPV disturbing the operative field, and 97.3% and 95% for a disturbing tributary, respectively. Each group had 50 SPVCs, with a total of 70 and 64 SPVs, 10 and 11 general SPVC configurations, as well as 29 and 28 different individual anatomical variations in groups 1 and 2, respectively. Both groups had 1-3 SPVs with a similar distribution of frequencies [Chi-square (4) = 27.56; p = 0.0145 (Fisher's exact test)]. The similarity of the general configurations was not statistically significant. The same four predominant configurations constituted 80% of the SPVCs in each group. The vein of the cerebellopontine fissure was most frequently found in 86% and 88% of cases, and a petrosal-galenic anastomosis was seen in 38% and 40% of groups 1 and 2, respectively. Individual SPVC variations are extensive. Good quality bFFE or equivalents are feasible for preoperative SPVC assessments. However, methods improving vascular visualization are recommended.


Association Between Hypertensive Disorders of Pregnancy and Dementia: a Systematic Review and Meta-Analysis.
Prior meta-analyses report a 2- to 4-fold increased risk of later cardiovascular disease among women with a history of hypertensive disorders of pregnancy (HDP). Given HDP's vascular underpinnings, it is hypothesized to also be a risk factor for later dementia. We aim to summarize the evidence for the impact of HDP on dementia and consider unique associations between HDP and dementia subtypes. Observational studies on the relationship between HDP and dementia were identified from online electronic databases to July 1, 2021 (PROSPERO identifier: CRD42020185630). We included observational studies published in English. Exposure among women was any HDP and HDP subtypes: gestational hypertension, preeclampsia/eclampsia, or other/unspecified HDP. Outcome was any dementia and dementia subtypes: Alzheimer's disease, vascular dementia, or other/unspecified dementias. For our primary analyses, we included 5 cohort studies with a total of 183 874 women with and 2 309 705 women without HDP. Pooled analysis found a 38% higher risk of all-cause dementia among women with, versus without, any type of HDP (adjusted hazard ratio, 1.38 [95% CI, 1.18-1.61]; P<0.01). When examining association by HDP and dementia subtypes, we found that women with, versus without, any type of HDP had over a 3-fold higher risk of vascular dementia (adjusted hazard ratio, 3.14 [95% CI, 2.32-4.24]; P<0.01). Our findings indicate that maternal history of HDP is an important risk factor for later development of vascular and all-cause dementia. Further research among more racially/ethnically diverse populations quantifying HDP's effect on all-cause dementia, and specifically vascular dementia, is warranted.


Expression and cellular distribution of baculovirus-expressed bovine herpesvirus 1 (BHV-1) glycoprotein D (gD) sequences.
Glycoprotein D (gD) of bovine herpesvirus 1 (BHV-1), a homolog of herpes simplex virus gD, represents a major component of the viral envelope and is a dominant immunogen. To study the antigenic properties of the different regions of gD, we have expressed the full-length gD encoding gene and overlapping fragments spanning various regions of the gD open reading frame in a baculovirus (Autographa californica nuclear polyhedrosis virus)--insect cell (Spodoptera frugiperda, SF-9) system. Maximum levels of expression for all proteins were obtained 48 to 72 h post infection of SF-9 cells by recombinant viruses. Full-length and truncated recombinant gD proteins reacted specifically with anti-gD monospecific serum as determined by immunoprecipitation and immunoblotting, indicating that the proteins retained their antigenicity. However, based on the reactivity with a panel of gD-specific monoclonal antibodies (Mabs), the full-length recombinant gD lacked proper expression for two highly neutralizing linear epitopes identified by Mabs R54 and 9D6. The rest of the epitopes appeared to be preserved and antigenically unaltered. Immunofluorescence studies of recombinant baculovirus infected SF-9 cells using gD monospecific serum, revealed no direct correlation between cellular localization of the expressed proteins and their amino acid sequences.


Skin deformation analysis for pre-operative planning of DIEAP flap reconstruction surgery.
Deep inferior epigastric artery perforator (DIEAP) flap reconstruction surgeries can potentially benefit from augmented reality (AR) in the context of surgery planning and outcomes improvement. Although three-dimensional (3D) models help visualize and map the perforators, the anchorage of the models to the patient's body during surgery does not consider eventual skin deformation from the moment of computed tomography angiography (CTA) data acquisition until the position of the patient while in surgery. In this work, we compared the 3D deformation registration from supine arms down (CTA position) to supine with arms at 90° degrees (surgical position), estimating the patient's skin deformation. We processed the data sets of 20 volunteers with a 3D rigid registration tool and performed a descriptive statistical analysis and statistical inference. With 2.45 mm of root mean square and 2.89 mm of standard deviation, results include 30% cases of deformation above 3 mm and 15% above 4 mm. Pose transformation deformation indicates that 3D surface data from the CTA scan position differs from data acquired in loco at the surgical table. Such results indicate that research should be conducted to construct accurate 3D models using CTA data to display on the patient, while considering projection errors when using AR technology.


Risk Factors for Heart Failure in the Community: Differences by Age and Ejection Fraction.
Differences in comorbid conditions in patients with heart failure compared with population controls, and whether differences exist by type of heart failure or age, have not been well documented. The prevalence of 17 chronic conditions were obtained in 2643 patients with incident heart failure from 2000 to 2013 and controls matched 1:1 on sex and age from Olmsted County, Minnesota. Logistic regression determined associations of each condition with heart failure. Among 2643 matched pairs (mean age 76.2 years, 45.6% men), the comorbidities with the largest attributable risk of heart failure were arrhythmia (48.7%), hypertension (28.4%), and coronary artery disease (33.9%); together these explained 73.0% of heart failure. Similar associations were observed for patients with reduced and preserved ejection fraction, with the exception of hypertension. The risk of heart failure attributable to hypertension was 2-fold higher in patients with heart failure with preserved ejection fraction (38.7%) than in patients with heart failure with reduced ejection fraction (17.8%). Hypertension, coronary artery disease, arrhythmia, and diabetes were more strongly associated with heart failure in younger (≤75 years) compared to older (>75 years) persons. Patients with heart failure have a higher prevalence of many chronic conditions than controls. Similar associations were observed in patients with reduced and preserved ejection fraction, with the exception of hypertension, which was more strongly associated with heart failure with preserved ejection fraction. Finally, some cardiometabolic risk factors were more strongly associated with heart failure in younger persons, highlighting the importance of optimizing prevention and treatment of risk factors and, in particular, cardiometabolic risk factors.


Task force: a management technique that produces quality decisions and employee commitment.
A task force is a technique that can be used by the dietitian-manager to develop solutions for specific, identified problems. Because employees are directly involved in the decision-making process, better solutions--ones that are also more acceptable to the work group--result. To implement a task force, management must plan the strategy: Select a facilitator, explain the concept and problem to the work group, select task force participants, and make meeting arrangements. The task force meetings should be structured to maximize efficiency and productivity. The plan of action is developed by the task force members; all decisions are based upon input from the work group. Successful implementation of the solutions is the responsibility of the task force. Applications for task forces in both the clinical and food management areas are numerous and result in both tangible and intangible benefits.


Influence of cognitive reserve in schizophrenia: A systematic review.
To perform a systematic review of the influence of sociobehavioural indicators of cognitive reserve (CR) in the risk of schizophrenia, the clinical manifestations of the disease, and cognitive intervention programs (CRT) carried out with these patients. A cross search was made by two independent reviewers in Pubmed and PsycINFO databases using keywords "schizophrenia" and "cognitive reserve." Twenty-one studies which analyzed different CR proxies were selected and the level of evidence was classified according to the Oxford Centre for Evidence-Based Medicine. People with higher CR may have a lower risk of developing schizophrenia and a later onset of disease. In addition, they present better neuropsychological and functional performance in the illness course. However, the suspected influence of CR on the effectiveness of CRT in patients with schizophrenia is currently unresolved. Our findings suggest that higher CR delays the clinical diagnosis threshold and severity of the symptoms in patients with schizophrenia. However, effect of singular sociobehavioral measures on clinical expression and benefits of intervention program need further investigation.


Identifying functional microRNAs in macrophages with polarized phenotypes.
Macrophages respond to external stimuli with rapid changes in expression of many genes. Different combinations of external stimuli lead to distinct polarized activation patterns, resulting in a spectrum of possible macrophage activation phenotypes. MicroRNAs (miRNAs) are small, noncoding RNAs that can repress the expression of many target genes. We hypothesized that miRNAs play a role in macrophage polarization. miRNA expression profiles were determined in monocyte-derived macrophages (MDMs) incubated in conditions causing activation toward M1, M2a, M2b, or M2c phenotypes. One miRNA guide strand and seven miRNA passenger strands were significantly altered. Changes were confirmed in MDMs from six separate donors. The amplitude of miRNA expression changes in MDMs was smaller than described studies of monocytes responding to inflammatory stimuli. Further investigation revealed this correlated with higher basal miRNA expression in MDMs compared with monocytes. The regulation of M1- and M2b-responsive miRNAs (miR-27a, miR-29b, miR-125a, miR-146a, miR-155, and miR-222) was similar in differentiated THP-1 cells and primary MDMs. Studies in this model revealed cross-talk between IFNγ- and LPS-associated pathways regulating miRNA expression. Furthermore, expression of M1-associated transcripts was increased in THP-1 cells transfected with mimics of miR-29b, miR-125a-5p, or miR-155. The apparent inflammatory property of miR-29b and miR-125a-5p can be at least partially explained by repression of TNFAIP3, a negative regulator of NF-κB signaling. Overall, these data suggest miRNAs can contribute to changes in macrophage gene expression that occur in different exogenous activating conditions.


Customized peptidoglycan surfaces to investigate innate immune recognition via surface plasmon resonance.
Glycan-protein interactions facilitate some of the most important biomolecular processes in and between cells. They are involved in different cellular pathways, cell-cell interactions and associated with many diseases, making these interactions of great interest. However, their structural and functional diversity poses great challenges in studying them at the molecular level. Surface plasmon resonance (SPR) technology presents great advantages to study glycan-protein interactions due to its superior sensitivity, ability to monitor real-time interactions, relatively simple data interpretation, and most importantly, direct measurement of binding without a need for fluorescent labeling. Here, another dimensionality of SPR in studying glycan-protein interactions is demonstrated via examples of binding between human innate immune receptors and their bacterial peptidoglycan ligands. In order to best resemble interactions in solution, a novel strategy of tethering the carbohydrate at different positions to the biosensor surface is applied to represent the potential displays of the carbohydrate ligand to the receptor. Subsequent kinetic analysis provides insights into the optimized configuration of peptidoglycan fragments for binding with its receptors. The manuscript contains a "how-to guide" to help with the implementation of these methods in other glycan-protein binding systems.


A new spectrophotometric assay for dopachrome tautomerase.
The existence of a new enzyme involved in mammalian melanogenesis has been recently reported. The names dopachrome oxidoreductase and dopachrome tautomerase have been proposed for the enzyme. So far, this enzyme has been assayed at 475 nm on the basis of its ability to catalyze dopachrome decoloration. This method presents two major problems, derived from the instability of the substrate (dopachrome): (1) dopachrome must be prepared immediately before use, and (2) the rate of dopachrome decoloration in the absence of the enzyme is not negligible, and, furthermore, is enhanced by non-enzymatic agents. In order to overcome these problems, we present a new procedure that combines: (1) a quantitative, fast and easy way to prepare dopachrome from L-dopa by sodium periodate oxidation; (2) a spectrophotometric method in the UV region, at 308 nm, based on following the absorbance increase due to the enzyme-specific tautomerization of dopachrome to 5,6-dihydroxyindole-2-carboxylic acid as opposed to the absorbance decrease due to the spontaneous decarboxylative transformation of dopachrome into 5,6-dihydroxyindole. The advantages of these methods as compared to the previously used procedures are discussed.


Inactivation of enteric adenovirus and feline calicivirus by ozone.
Little information is available regarding the effectiveness of ozone on the inactivation of caliciviruses and enteric adenoviruses. Inactivation experiments were conducted with feline calicivirus (FCV), closely related to the human caliciviruses based on nucleic acid organization and capsid architecture, and adenovirus type 40 (AD40). Experiments were carried out in buffered disinfectant demand free water at pH 7 and 5 degrees C. Ct values; concentration of ozone multiplied by contact time with virus; were determined from application of the efficiency factor hom (EFH) model. Ct values for 4-log (99.99%) ozone inactivation at 5 degrees C and pH 7 ranged from 0.07 to 0.60 mg/l min for AD40 and <0.01 to 0.03 mg/l min for FCV. Ct values listed in the US environmental protection agency "Guidance Manual for Compliance with Filtration and Disinfection Requirements for Public Water Systems Using Surface Water Sources" were higher than Ct values generated by this study. Very low ozone residuals (<0.01(mg/l) substantially inactivated FCV and AD40 under the studied conditions.


The course of experimental myocardial infarction under conditions of Suppressed and enhanced NO synthesis.
Experimental myocardial infarction (coronary ligation without drug infusion) reduced heart rate, stroke volume, cardiac output, and blood pressure. Under conditions of blocked NO synthesis, experimental myocardial infarction was accompanied by a transient increase in heart rate, stroke volume, cardiac output, and blood pressure, followed by their decrease throughout the experiment. Experimental myocardial infarction against the background of L-arginine treatment increased all these parameters with their subsequent stabilization at the attained level. Animal survival after administration of L-arginine was 80% vs. 33 in the control, and 22% after administration of L-NAME. It can be hypothesized that L-arginine possesses an intrinsic NO-independent cardioprotective effect.


Capturing the Polarization Response of Solvated Proteins under Constant Electric Fields in Molecular Dynamics Simulations.
We capture and compare the polarization response of a solvated globular protein ubiquitin to static electric (E-fields) using atomistic molecular dynamics simulations. We collectively follow E-field induced changes, electrical and structural, occurring across multiple trajectories using the magnitude of the protein dipole vector (Pp ). E-fields antiparallel to Pp induce faster structural changes and more facile protein unfolding relative to parallel fields of the same strength. While weak E-fields (0.1-0.5 V/nm) do not unfold ubiquitin and produce a reversible polarization, strong E-fields (1-2 V/nm) unfold the protein through a pathway wherein the helix:β-strand interactions rupture before those for the β1-β5 clamp. Independent of E-field direction, high E-field induced structural changes are also reversible if the field is switched off before Pp exceeds 2 times its equilibrium value. We critically examine the dependence of water properties, protein rotational diffusion and E-field induced protein unfolding pathways on the thermostat/barostat parameters used in our simulations.


Culturally sensitive AIDS educational videos for African American audiences: effects of source, message, receiver, and context.
The importance of using culturally sensitive educational materials in HIV-related interventions with racial and ethnic minority groups is widely recognized. However, little empirical research has been conducted to assess the relative effectiveness of different techniques for creating culturally sensitive AIDS educational videos. Two field experiments with three samples of African American adults (N = 174, 173, and 143) were conducted to assess how source characteristics (race of communicator), message characteristics (multicultural message vs. culturally specific message), and audience characteristics (racial distrust and AIDS-related distrust) influence proximate (perceptions of the message's credibility and attractiveness) and distal (AIDS-related attitudes, beliefs, and behavioral intentions) output variables for AIDS educational videos. In Study 1, an AIDS video with a culturally specific message was rated as more credible, more attractive, and of higher quality than was a video with a multicultural message. The multicultural message was rated less favorably when delivered by a White announcer than when the announcer was Black. In Study 2, the same pattern was replicated with a second community sample and a campus-based sample. Study 2 also indicated that a multicultural message might be more effective if delivered in a culturally specific context, namely, after audience members watch a culturally specific video. Minimal changes were observed in distal outcome variables. It is argued that influencing proximate output variables is necessary, though not sufficient, for effecting long-term change in AIDS-related attitudes, beliefs, and behaviors.


Supervisor Cultural Humility and Supervisee Nondisclosure: The Supervisory Working Alliance Matters.
Given that half or more of supervisees (therapist trainees) never have their clinical work monitored or observed, supervisees who withhold salient information in clinical supervision compromise supervisors' ability to monitor client welfare and promote supervisees' professional development. Attempting to further understand the factors explaining supervisee nondisclosure, we tested the supervisory working alliance as a mediator of the hypothesized inverse relations of cultural humility and collaborative supervision with supervisee nondisclosure (supervision-related and clinically-related nondisclosure) among a diverse sample of 214 supervisees in applied psychology and allied mental health programs. Results supported the hypotheses that (1) descriptively, supervision-related nondisclosure was more prominent than clinically-related nondisclosure, (2) cultural humility substantially inversely predicted supervisee nondisclosure, and (3) the supervisory working alliance fully mediated the inverse relations of cultural humility and collaborative supervision with supervisee nondisclosure. Understanding the mechanisms underlying supervisee nondisclosure have broad implications for clinicians and researchers alike.


Mechanisms that underlie blood flow regulation at rest and during exercise.
The cardiovascular system must distribute oxygen and nutrients to the body while maintaining appropriate blood pressure. This is achieved through a combination of central and peripheral mechanisms that influence cardiac output and vasomotor tone throughout the vascular system. Furthermore, the capability to preferentially direct blood to tissues with increased metabolic demand (i.e., active hyperemia) is crucial to exercise tolerance. However, the interaction between these systems is difficult to understand without real-life examples. Fortunately, monitoring blood flow, blood pressure, and heart rate during a series of laboratory protocols will allow students to partition the contributions of these central and peripheral factors. The three protocols include 1) reactive hyperemia in the forearm, 2) small muscle mass handgrip exercise, and 3) large muscle mass cycling exercise. In addition to providing a detailed description of the required equipment, specific protocols, and expected outcomes, this report also reviews some of the common student misconceptions that are associated with the observed physiological responses.NEW & NOTEWORTHY Blood flow regulation during exercise is a complicated process that involves many overlapping mechanisms. This laboratory will help students better understand how the body regulates blood flow to the active muscles using three separate protocols: 1) reactive hyperemia, 2) small muscle mass exercise, and 3) large muscle mass exercise.


A Rare Case of Primary Tuberculous Otitis Media with Bezold's Abscess.
Tuberculous Otitis Media is a rare clinical presentation. The signs and symptoms are variable that leads to delayed diagnosis and treatment. Persistent ear discharge not responding to topical and systemic antibiotics should be considered for investigation of tuberculosis. We report a case of Primary Tuberculous Otitis Media who presented with Bezold's Abscess. Patient underwent Mastoidectomy. Diagnosis was made with the Histopathological examination of the suspicious extensive pale granulation tissue. Patient was started on ATT immediately. Greater awareness regarding the disease is needed to make an early diagnosis. Late diagnosis increases the risk of complications. Anti Tubercular Therapy is the treatment of choice. Surgical intervention may be added to drug therapy. In cases with complications, radical surgery will be needed. Bezold's abscess is a rare complication of Otitis Media. CT imaging should be considered in suspected neck abscess patients with history of ear discharge to rule out aural cause of abscess.


Pelvic floor muscle training for urgency urinary incontinence in women: a systematic review.
The objective of this study is to evaluate the effectiveness of existing physiotherapy modalities for the treatment of urge urinary incontinence (UUI). A systematic review was performed for primary studies of physiotherapy techniques for UUI published in English between 1996 and August 2010 in major electronic databases. Only randomized clinical trials that reported outcomes separately for women with UUI were included. Outcomes assessed were reduction in UUI, urinary frequency, and nocturia. Data from 13 full-text trials including the modalities of pelvic floor muscles exercises with or without biofeedback, vaginal electrical stimulation, magnetic stimulation, and vaginal cones were analyzed. The methodologic quality of these trials was fair. Significant improvement in UUI was reported for all physiotherapy techniques except vaginal cone therapy. There are insufficient data to determine if pelvic physiotherapy improves urinary frequency or nocturia. Evidence suggests that physiotherapy techniques may be beneficial for the treatment of UUI.


Neural factors in experimental degenerative arteriopathy.
Intermittent electrical stimulation of the lateral hypothalamus of rats performed for 30 min to 6 hr, results in hyperlipidemia and endothelial cell damage of the aorta and coronary arteries. Hyperlipidemia is related to transient biliary obstruction elicited by hypothalamic stimulation and is characterized by elevation of the cholesterol, phospholipid, and triglyceride fractions. Endothelial cell damage is observed ultrastructurally as plasma membrane degeneration with detachment and the formation of large spaces ("vacuoles"). Thus, neural factors may be implicated in inducing conditions associated with early atherogenesis. Stimulation carried out for longer time intervals would be expected to produce more advanced lesions. However, the role of neural transmission per se (i.e., without hyperlipidemia) in producing arteriopathy is not clearly defined from these experiments. In rats, the lesser splanchnic nerve forms the major innervation of the abdominal aorta. In animals fed normal diets, chronic intermittent stimulation of this nerve (up to 3 weeks) resulted in advanced arteriosclerotic changes with intimal fibrosis and calcification. On histologic examination, lipid deposits appeared to be absent from these lesions. Animals stimulated for shorter periods of time exhibited earlier changes associated with atherogenesis, such as endothelial damage, elastic reduplication, and adherent microthrombi. Thus, direct neural transmission, especially if excessive, plays a role in producing arteriopathy. Hyperlipidemia, if persistent, could modify these lesions so that they would accumulate plasma lipids. Experiments to test this hypothesis are currently in progress.


A method for simulating the reflex output of a motoneuron pool.
An analysis of the reflex output of a motoneuron pool in response to a Ia-afferent input is presented. The analysis is based upon a model of the motoneuron pool which includes the subthreshold behavior of motoneurons (integration of synaptic inputs) and the statistical distribution of the motoneurons according to their resting conductance. The latter feature allows for the orderly recruitment of the motoneurons in the order of low resting conductance to high resting conductance. The number of active motoneurons (i.e. the excitation level) is determined by the balance of the excitatory and inhibitory conductances acting on the pool. The reflex output in response to a Ia-EPSP is computed at various excitation levels and with different amounts of presynaptic inhibition. The reflex output is the same for a given excitation level, regardless of the mixture of excitatory and inhibitory postsynaptic conductances used to produce that excitation level. In contrast, presynaptic inhibition markedly affects the relation between reflex output and excitation level.


Cyclical mitochondrial deltapsiM fluctuations linked to electron transport, F0F1 ATP-synthase and mitochondrial Na+/Ca+2 exchange are reduced in Alzheimer's disease cybrids.
Reduced complex IV, increased oxidative stress and beta amyloid peptide secretion in Alzheimer's disease (AD) can be replicated in cybrid models. We characterized cyclical mitochondrial deltapsiM fluctuations ('flickering') in neuroblastoma cells and AD/CTL cybrids. Flickering was blocked by ATP-synthase inhibition, was not observed in rho0 cells and was not blocked by antioxidant treatment. Flickering was not affected by the Ca(+2) uniporter antagonist Ru360 but was eliminated by BAPTA or CGP37137 blockade of the mitochondrial Na(+)/Ca(+2) exchanger. AD cybrid mitochondria showed reduced flickering. Flickering seems to represent coupling of deltapsiM to F0F1 ATP-synthase; reduction of flickering in AD cybrids suggests dysfunction of this coupling.


Erratum: Development and Reorganization of Orientation Representation in the Cat Visual Cortex: Experience-Dependent Synaptic Rewiring in Early Life.
[This corrects the article DOI: 10.3389/fninf.2020.00041.].


Making (anti-) sense out of huntingtin levels in Huntington disease.
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder, characterized by motor, psychiatric and cognitive symptoms. HD is caused by a CAG repeat expansion in the first exon of the HTT gene, resulting in an expanded polyglutamine tract at the N-terminus of the huntingtin protein. Typical disease onset is around mid-life (adult-onset HD) whereas onset below 21 years is classified as juvenile HD. While much research has been done on the underlying HD disease mechanisms, little is known about regulation and expression levels of huntingtin RNA and protein. In this study we used 15 human post-mortem HD brain samples to investigate the expression of wild-type and mutant huntingtin mRNA and protein. In adult-onset HD brain samples, there was a small but significantly lower expression of mutant huntingtin mRNA compared to wild-type huntingtin mRNA, while wild-type and mutant huntingtin protein expression levels did not differ significantly. Juvenile HD subjects did show a lower expression of mutant huntingtin protein compared to wild-type huntingtin protein. Our results in HD brain and fibroblasts suggest that protein aggregation does not affect levels of huntingtin RNA and protein. Additionally, we did not find any evidence for a reduced expression of huntingtin antisense in fibroblasts derived from a homozygous HD patient. We found small differences in allelic huntingtin mRNA levels in adult-onset HD brain, with significantly lower mutant huntingtin mRNA levels. Wild-type and mutant huntingtin protein were not significantly different in adult-onset HD brain samples. Conversely, in juvenile HD brain samples mutant huntingtin protein levels were lower compared with wild-type huntingtin, showing subtle differences between juvenile HD and adult-onset HD. Since most HD model systems harbor juvenile repeat expansions, our results suggest caution with the interpretation of huntingtin mRNA and protein studies using HD cell and animal models with such long repeats. Furthermore, our huntingtin antisense results in homozygous HD cells do not support reduced huntingtin antisense expression due to an expanded CAG repeat.


Interactions of species in an Anabaena flos-aquae association from the Plußsee (East-Holstein, Federal Republic of Germany).
Fluorescent probes have been applied to study by epifluorescence microscopy interactions between species in an Anabaena flos-aquae association, derived from a freshwater community. Glycoconjugates (macromolecules containing carbohydrate residues) have been shown to play a vital role in recognition processes and in formation of attachment sites between cells. By use of a group of proteins (lectins) with specific affinities to certain sugar residues we were able to clucidate specific patterns expressed at cellular surfaces, thereby indicating the physiological state of a cell. Low molecular weight fluorochromes, like the fluorescent brightener calcofluor white have been shown to be extremely useful tools for visualizing structural entities (and species) which otherwise escape notice by microscopy. We have demonstrated that the decline of the bloom of Anabaena flos-aquae was caused or at least accelerated by action of a fungus (chytrid). We also proved that the shell (lorica) of a choanoflagellate most likely is built from chitin.


Pathway and protein engineering approaches to produce novel and commodity small molecules.
Nature has provided us the basis of designing the most integrated and efficacious production platforms. Cell factories via their millions of years of evolution have nearly perfected each of their production systems. We have been trying to imitate, utilize and tweak this system to our advantage by using slightly overlapping and greatly interdependent approaches such as metabolic engineering and systems biology to make nature work for us in an efficient and robust way, without producing toxic waste and/or unnecessary side products. Systems biology, metabolic engineering and 'omics' technologies have paved the way for protein and pathway engineering. To this end we will talk about the recent advances in production of novel pharmaceutical and commodity small molecules by designing novel proteins and pathways.