Sulfurimicrobium lacus gen. nov., sp. nov., a sulfur oxidizer isolated from lake water, and review of the family Sulfuricellaceae to show that it is not a later synonym of Gallionellaceae.
A facultatively anaerobic sulfur-oxidizing bacterium, strain skT11T, was isolated from anoxic lake water of a stratified freshwater lake. As electron donor for chemolithoautotrophic growth, strain skT11T oxidized thiosulfate, tetrathionate, and elemental sulfur under nitrate-reducing conditions. Oxygen-dependent growth was observed under microoxic conditions, but not under fully oxygenated conditions. Growth was observed at a temperature range of 5-37 °C, with optimum growth at 28 °C. Strain skT11T grew at a pH range of 5.1-7.5, with optimum growth at pH 6.5-6.9. Heterotrophic growth was not observed. Major components in the cellular fatty acid profile were C16:1 and C16:0. The complete genome of strain skT11T consisted of a circular chromosome with a size of 3.8 Mbp and G + C content of 60.2 mol%. Phylogenetic analysis based on the 16S rRNA gene sequences indicated that the strain skT11T is related to sulfur-oxidizing bacteria of the genera Sulfuricella, Sulfurirhabdus, and Sulfuriferula, with sequence identities of 95.4% or lower. The analysis also indicated that these three genera should be excluded from the family Gallionellaceae, as members of another family. On the basis of its genomic and phenotypic properties, strain skT11T (= DSM 110711 T = NBRC 114323 T) is proposed as the type strain of a new species in a new genus, Sulfurimicrobium lacus gen. nov., sp. nov. In addition, emended descriptions of the families Gallionellaceae and Sulfuricellaceae are proposed to declare that Sulfuricellaceae is not a later synonym of Gallionellaceae.


Neuropsychiatric comorbidities in Huntington's and Parkinson's Disease: A United States claims database analysis.
Huntington's disease is a rare, genetic, neurodegenerative disease characterized by a triad of cognitive, behavioral, and motor symptoms. The condition gradually results in increasing disability, loss of independence, and ultimately death. Our objective was to use United States claims data (which offer valuable insight into the natural history of disease) to compare the prevalent comorbidities of people with Huntington's disease against matched controls with Parkinson's disease or with no major neurodegenerative diseases (general population controls). We also assess medication use in people with Huntington's disease. This was a retrospective, observational study using data from the IBM MarketScan® Databases. Cases and controls were matched 1:1, and comorbidities were analyzed in each group during 2017. Medications were also assessed in the Huntington's disease cohort. Eligible cases had ≥ 2 diagnostic codes for Huntington's disease; controls had ≥ 2 codes for Parkinson's disease (with no record of Huntington's disease), or, for general population controls, no record of Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, or dementia. A total of 587 matched individuals were assessed in each cohort. Depression and anxiety were more common in Huntington's disease versus Parkinson's disease (odds ratios: 1.51 and 1.16, respectively). Other conditions more common in Huntington's disease included dementia, communication/speech problems, dysphagia, and falls. The use of antidepressant (59.9%) and antipsychotic (39.5%) medications was frequent among Huntington's disease cases. These data highlight the prevalence of psychiatric, cognitive, communication, swallowing, and mobility problems in people with Huntington's disease, underscoring the need for holistic expert care of these individuals.


In vivo and in vitro degradation of monofilament absorbable sutures, PDS and Maxon.
Two new absorbable monofilament suture materials polydioxanone and Maxon are being employed increasingly in abdominal surgery because of increased strength retention and decreased tissue reactivity compared with previously available materials. As part of our investigation of the behaviour of suture materials, 3-0 sutures of polydioxanone and Maxon were enclosed in nylon pouches, a technique developed for in vivo experiments to prevent cellular interaction with implanted devices. The pouched sutures were gas sterilized, then implanted in either the extrafascial space or peritoneal cavity for periods of 1-5 wk. Sterilized sutures were also incubated in Ringer's lactate at 37 degrees C. Tensile strength of the exposed sutures was measured. For a given suture material and duration of incubation, there was no significant difference in tensile strength degradation among the three test environments. Although the strength of unexposed Maxon is greater than that of polydioxanone, the residual strength of Maxon decreases more rapidly in use, so that, after 2 wk, the strength of polydioxanone is greater. Scanning electron microscope examination of the suture surfaces reveals that polydioxanone develops surface crazing with time, whereas the surface morphology of Maxon remains relatively unaltered.


Conversion of α-lactose monohydrate to anhydrous form with superior tabletability by twin-screw extrusion at elevated temperature.
The purpose of this study was to improve tabletability (tensile strength versus compaction pressure) of α-lactose monohydrate by twin screw extrusion (TSE) near its dehydration temperature but below its melting point. When extruded at 150 and 160 °C, α-lactose monohydrate converted completely to α-lactose anhydrous that was mostly crystalline and only partially amorphous; the latter was indicated by glass transition observed in DSC scans. Tabletability of the material thus obtained by TSE was superior to anhydrous lactose available commercially or produced by hot air oven drying at 160 °C. The superior tabletability was attributed to the partial conversion to amorphous lactose. When samples of anhydrous lactose powders obtained by TSE or oven drying were exposed to 25 °C/60% RH and 40 °C/75% RH, they reverted to the monohydrate with decreased tabletability. However, when anhydrous lactose powders produced by TSE were first compressed into tablets with high tensile strength and then exposed to similar stability testing conditions, there was no decrease in the tensile strength of tablets. Rather, it further increased, possibly due to the interaction of the amorphous fraction of lactose with moisture. Thus, TSE not only increased tabletability of α-lactose monohydrate, the compressed tablets remained intact and hard during shelf-life. These results demonstrate that a new modified anhydrous lactose may be produced by TSE that has better tabletability and superior physical stability than α-lactose monohydrate and the commercially available anhydrous lactose.


Alterations in mucosal content of colonic glycoconjugates in inflammatory bowel disease defined by monoclonal antibodies.
The presence of several glycoconjugates in colonic mucosa of patients with inflammatory bowel disease was assessed through indirect immunofluorescent staining using a collection of 23 monoclonal antibodies directed against human colonic mucin glycoproteins (anti-HCM MAbs). Intensity and distribution of staining by three anti-HCM MAbs were significantly altered in mucosa from patients with ulcerative colitis (UC) (n = 14) when compared with normal tissue (n = 15) and with tissue from patients with Crohn's disease as well as other inflammatory disorders (n = 15). Staining by anti-HCM MAb 17, which binds to colonic mucin glycoprotein species IV and V, was absent or diminished in 86% of samples from patients with active UC in contrast to 14% of normal and disease control specimens. Reduction in anti-HCM MAb 17 staining was less marked in mucosal biopsy specimens from patients with UC lacking acute inflammatory activity (n = 8). In contrast to the apparent loss of the MAb 17-defined epitopes, staining with anti-HCM MAbs 10 and 22 was enhanced in UC tissue compared with normal and disease controls. Increased staining with MAb 10 was present in 93% of samples from UC patients demonstrating active inflammation. Increased MAb 10 staining was not apparent in noninvolved mucosa from UC patients, indicating that increased expression of the specified epitope is related to the acute inflammatory process. In contrast, indirect immunofluorescent staining with MAb 22 was apparent in both involved (78%) and uninvolved (67%) UC mucosa in contrast to normal and disease controls (less than 12%). In addition, staining with several other anti-HCM MAbs (MAbs 3, 11, 15) was modestly and variably diminished (14%-28%) in UC, Crohn's disease, and other inflammatory disorders. These findings demonstrate the presence of alterations in mucosal content of specific glycoconjugate structures in association with UC. Inflammatory processes may also result in broad changes in glycoconjugate determinants generally.


A novel approach to CSF pressure measurement via lumbar puncture that shortens the measurement time with a high level of accuracy.
Intracranial pressure (ICP) is an important parameter in clinical management and diagnosis of several neurological diseases which is indirectly measured via lumbar puncture (LP). In routine measurements of cerebrospinal fluid pressure (PCSF) from lumbar region, a spinal needle and a spinal manometer are used. PCSF measurement via LP with the use of a spinal manometer may not yield correct PCSF results due to prolonged times required to obtain an accurate pressure value. Equilibrium pressure may be underestimated in circumstances where spinal manometry procedure is terminated prematurely, with the wrong assumption that equilibrium pressure is reached. Elevated PCSF levels can lead to visual loss and brain damage when go undiagnosed. In this study, the spinal needle-spinal manometer combination was modelled with a first-order differential equation and a time constant (τ) was defined as the product of the resistance to flow of the needle with the bore area of the manometer divided by the dynamic viscosity of CSF, i.e. τ= RA/ρCSF. Each needle/manometer combination had a unique constant as a predictor of the equilibrium pressure. The fluid pressure in the manometer rose in an exponential manner which was tested in a simulated environment using 22G spinal needles namely Braun-Spinocan, Pajunk-Sprotte and M.Schilling. Curve fitting of the manometer readings were obtained with regression coefficients of R2 ≥ 0.99 to determine measurement time constants. The residual differences between predicted and true values were less than 1.18 cmH2O. For a given needle/manometer combination, time required to reach equilibrium pressure was identical for all pressure levels. PCSF measured at reduced times can easily be interpolated to their equilibrium level allowing clinicians to obtain PCSF values with high accuracy within seconds. This method can be used as an indirect estimation of ICP in routine clinical practice.


Antiarrhythmic plasma-concentration range of imipramine against ventricular premature depolarizations.
The antiarrhythmic plasma-concentration range of imipramine with desmethylimipramine was determined in 15 cardiac patients with ventricular arrhythmias. When more than 80% efficacy was reached, subjects' plasma concentrations of imipramine and desmethylimipramine were determined by gas chromatography. The imipramine dose required for suppression of ventricular premature depolarizations (VPDs) ranged from 50 to 400 mg a day (1.6 to 3.9 mg/kg/day). Peak plasma imipramine concentration was reached at 2.5 +/- 0.92 hr and peak plasma desmethylimipramine concentration at 4.1 +/- 2.8 hr after imipramine. At 80%, VPD suppression, mean steady-state plasma concentration of imipramine with desmethylimipramine ranged from 74 to 385 ng/ml. The ratio of plasma imipramine to desmethylimipramine ranged from 0.5 to 5.5 (median = 1.3). The elimination t1/2 for the parent compound, imipramine, ranged from 4 to 14.4 hr. Imipramine is an effective antiarrhythmic drug with sustained duration of action, although its elimination t1/2 is relatively short.


Retraction notice to: The effect of parenteral testosterone administration prior to hypospadias surgery: A prospective, randomized and controlled study [J Pediatr Urol 11 (2015) 143.e1-143.e6].
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Readers of the journal highlighted issues with the study design and statistical analysis of the results which affected the validity of the findings in the paper. Further review by the editors and journal statistician confirmed that there were issues in the paper that needed to be addressed. The authors were given the opportunity to address the problems in the paper but did not respond.


Long-term prognosis of medically treated patients with vasospastic angina and no fixed significant coronary atherosclerosis.
The clinical course of 48 consecutive patients with vasospastic angina and minor coronary atherosclerosis (no stenoses greater than 50%) was analyzed during an average follow-up period of 47 months. The study group consisted of 37 men and 11 women. Patients were treated with usual doses of calcium antagonists. One patient died (2%) and three had myocardial infarctions (6%). Seventy-one percent were asymptomatic or had infrequent angina; 13% had recurrences but had periods of remission lasting at least 10 months. Only 16% had persistent angina. None of the clinical or angiographic findings at the time of diagnosis were predictive of myocardial infarction or death, and they could not separate angina-free patients from those with recurrences. Thus, vasospastic angina without fixed coronary narrowing has a good prognosis despite the possibility of recurrences. However, there is a slight risk of myocardial infarction and death. This fact should be considered if there are plans to discontinue treatment.


Child psychopathic traits moderate relationships between parental affect and child aggression.
Previous studies show that children with psychopathic traits may be less responsive to parenting. Although harsh/inconsistent parenting is associated with increased problem behaviors in children low on psychopathic traits, children high on psychopathic traits show consistently high levels of problem behavior regardless of negative parenting. Moderating effects of child psychopathic traits on positive dimensions of parenting have not been explored. We applied multi-level regression models to test for interactions between child psychopathic traits and both positive and negative parental affect on individual differences in both reactive and proactive aggression, in a community-based sample of 1,158 children aged 9 through 10 years of age. There were significant associations between child psychopathic traits and positive and negative parental affect with both forms of aggression. Child psychopathic traits also moderated effects of positive and negative parental affect. Children low on psychopathic traits showed decreasing reactive aggression as positive parental affect increased, and increasing levels of reactive aggression as negative parental affect increased, but children high on psychopathic traits showed more stable levels of reactive aggression regardless of levels of parental affect. Proactive aggression was more strongly associated with negative parental affect among children with higher levels of psychopathic traits. In a community sample of preadolescent children, child psychopathic traits were shown to moderate the effects of parental affect on aggression. Reactive aggression in children high on psychopathic traits appears less responsive to variations in either positive or negative parenting. In contrast, child psychopathic traits may exacerbate the effects of high levels of negative parental effect on proactive aggression.


Atypical Presentation of Ocular Toxoplasmosis: A Case Report of Exudative Retinal Detachment and Choroidal Ischemia.
A 24-year-old healthy male presented with a chief complaint of blurred vision in the right eye for 1-week. Fundus examination indicated right exudative retinal detachment and choroidal ischemia. The patient responded well to anti-toxoplasmosis medications and steroids. Exudative retinal detachment and choroidal ischemia are atypical presentations of ocular toxoplasmosis. However, both conditions responded well to anti.parasitic therapy with steroid.


Identifying gaps in vaccination perception after mandating the COVID-19 vaccine in Saudi Arabia.
The burden of COVID-19 pandemic affected the globe, and it is unclear how it has impacted the general perception of other vaccines. We aimed to investigate the public awareness, knowledge, and attitude towards other complementary vaccines after the mandate of the COVID-19 vaccine. A cross-sectional study was conducted in Saudi Arabia using a survey distributed via several social media platforms in June 2022. The questionnaire had three main sections; awareness; attitudes; and demographic information. Descriptive analysis was mainly used and supplemented with Chi-square test for correlation. All individuals over the age of 18 were eligible to participate in the study. A total of 1,045 participants from Saudi Arabia completed the survey. Of the respondents, 55.9% were female, and 95% were Saudi citizens. Public awareness towards vaccines after the mandate of COVID-19 vaccine was the highest with the influenza vaccine (98.2%), followed by human papillomavirus (HPV) (40.7%), tetanus, diphtheria, and pertussis (Tdap) (37.2%), and lastly, pneumococcal vaccine (17%). More than 50% of the participants expressed their willingness to receive any of the four vaccines if they knew about the benefits related to these vaccines. The study showed that participants were willing to receive the vaccination if they were aware of the general benefits of vaccinations. Therefore, health education and campaigns toward recommended vaccines for high-risk group are essential and needed.


Localization of vasoactive intestinal peptide immunoreactivity in human foetus and newborn infant spinal cord.
Using an indirect immunofluorescence method the distribution of vasoactive intestinal peptide (VIP) immunoreactivity was studied in human foetus and newborn infant spinal cord and dorsal root ganglia. Further, for comparison some newborn infant brains were also investigated. Vasoactive intestinal peptide-like immunoreactive fibres were exclusively found in the caudal spinal cord and corresponding dorsal root ganglia. No immunoreactive cell bodies were detected. The first appearance of VIP-like immunoreactive fibres in both spinal cord and dorsal root ganglia was suggested during the fourth month of foetal life. Most immunolabelled fibres, concentrated in the sacral segment, were distributed in the Lissauer tract, along the dorsolateral gray border, in the intermediolateral areas and near the central canal in the dorsolateral commissure. A few VIP-like immunoreactive fibres were also seen in the dorsal funiculus and occasionally in the ventral gray horn and ventral roots. Further, a large population of VIP-like immunoreactive fibres occurs longitudinally in dorsal root, in ganglia and in the spinal nerve exit zone. These findings indicate the early appearance of VIP-like immunoreactive fibres in the human foetus spinal cord and corresponding ganglia. Moreover, they emphasize that in both foetus and newborn infant spinal cord VIP-like immunoreactive fibre distribution is limited to the lumbosacral segment.


ROS directly activates transforming growth factor β type 1 receptor signalling in human vascular smooth muscle cells.
Widely used NAPDH oxidase (Nox) inhibitor, apocynin is a prodrug that needs to be converted to its pharmacologically active form by myeloperoxidase. In myeloperoxidase deficient non phagocytic cells such as vascular smooth muscle cells (VSMCs) apocynin stimulates the production of ROS. ROS is generated by the activation of many signalling pathways, thus we have used apocynin as a pharmacological tool to characterise the role of endogenous ROS in activating the transforming growth factor beta receptor (TGFBR1) without the activation of other pathways. The in vitro study utilized human VSMCs. Western blotting and quantitative real time PCR were performed to assess signalling pathways and gene expression, respectively. Intracellular ROS levels was measured using fluorescence detection assay. Treatment with apocynin of human VSMCs stimulated ROS production and the phosphorylation of TGFBR1 and subsequent activation of TGFBR1 signalling leading to the formation of phosphorylated Smad2 which consequently upregulates the mRNA expression of glycosaminoglycan synthesizing enzyme. These findings outline a specific involvement of ROS production in TGFBR1 activation. Furthermore, because apocynin stimulates Nox and ROS production, apocynin must be used with considerable care in vitro as its actions clearly extend beyond the stimulation of Nox enzymes and it has consequences for cellular signalling. Apocynin can stimulate Nox leading to the production of ROS and the outcome is completely dependent upon the redox properties of the cell.


In vitro activity of the ketolide HMR 3647 (RU 6647) for Legionella spp., its pharmacokinetics in guinea pigs, and use of the drug to treat guinea pigs with Legionella pneumophila pneumonia.
The activities of HMR 3647, HMR 3004, erythromycin, clarithromycin, and levofloxacin for 97 Legionella spp. isolates were determined by microbroth dilution susceptibility testing. Growth inhibition of two Legionella pneumophila strains grown in guinea pig alveolar macrophages was also determined. The concentrations required to inhibit 50% of strains tested were 0.06, 0.02, 0.25, 0.03, and 0.02 microg/ml for HMR 3647, HMR 3004, erythromycin, clarithromycin, and levofloxacin, respectively. BYEalpha broth did not significantly inhibit the activities of the drugs tested, as judged by the susceptibility of the control Staphylococcus aureus strain; however, when Escherichia coli was used as the test strain, levofloxacin activity tested in BYEalpha broth was fourfold lower. HMR 3647, HMR 3004, erythromycin, and clarithromycin (0.25 and 1 microg/ml) reduced bacterial counts of two L. pneumophila strains grown in guinea pig alveolar macrophages by 0.5 to 1 log10, but regrowth occurred over a 2-day period. HMR 3647, erythromycin, and clarithromycin appeared to have equivalent intracellular activities which were solely static in nature. HMR 3004 was more active than all drugs tested except levofloxacin. In contrast, levofloxacin (1 microg/ml) was bactericidal against intracellular L. pneumophila and significantly more active than the other drugs tested. Therapy studies with HMR 3647 and erythromycin were performed in guinea pigs with L. pneumophila pneumonia. When HMR 3647 was given (10 mg/kg of body weight) by the intraperitoneal route to infected guinea pigs, mean peak plasma levels were 1.4 microg/ml at 0.5 h and 1.0 microg/ml at 1 h postinjection. The terminal half-life phase of elimination from plasma was 1.4 h. All 16 L. pneumophila-infected guinea pigs treated with HMR 3647 (10 mg/kg/dose given intraperitoneally once daily) for 5 days survived for 9 days after antimicrobial therapy, as did all 16 guinea pigs treated with the same dose of HMR 3647 given twice daily. Fourteen of 16 erythromycin-treated (30 mg/kg/dose given intraperitoneally twice daily) animals survived, whereas 0 of 12 animals treated with saline survived. HMR 3647 is effective against L. pneumophila in vitro, in infected macrophages, and in a guinea pig model of Legionnaires' disease. HMR 3647 given once daily should be evaluated as a treatment for Legionnaires' disease in humans.


Implications of adrenomedullin expression in the invasion of squamous cell carcinoma of the uterine cervix.
Adrenomedullin (AM) is a multifunctional peptide involved in a variety of physiological functions, including vasodilatation, growth regulation, and carcinogenesis. To elucidate the possible role of AM in the growth and invasion of uterine cervical carcinoma, the presence and distribution of AM and AM mRNA was examined in the neoplastic changes of squamous epithelium of the uterine cervix. The expression of AM mRNA by CaSki, a uterine squamous cell carcinoma cell line, was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). The presence and distribution of AM and AM mRNA in sections of normal cervical tissues, cervical intraepithelial neoplasia (CIN), and invasive squamous cell carcinomas were evaluated by immunohistochemical staining with a specific antibody against AM and by in situ RT-PCR, respectively. AM mRNA expression in CaSki cells was demonstrated by RT-PCR. Immunohistochemical staining for AM and in situ RT-PCR revealed that AM and AM mRNA were expressed in invasive squamous carcinoma cells, but not in normal cervical epithelium or in CIN lesions. Abundant expression of AM and AM mRNA was localized in the cytoplasm of carcinoma cells of bulky invasive carcinomas, while in early invasive carcinoma, the expression of AM and AM mRNA was more prominent in stromal cells adjacent to the early invasive carcinoma cells than in the carcinoma cells themselves. Because AM expression was evident only in invasive cervical squamous carcinoma cells and the stromal cells adjacent to early invasive carcinomas, it is likely that AM may play an important role in the growth and invasion of squamous cell carcinoma of the uterine cervix.


Development of a Machine Learning Algorithm to Predict Nonroutine Discharge Following Unicompartmental Knee Arthroplasty.
Reliable and effective prediction of discharge destination following unicompartmental knee arthroplasty (UKA) can optimize patient outcomes and system expenditure. The purpose of this study is to develop a machine learning algorithm that can predict nonhome discharge in patients undergoing UKA. A retrospective review of a prospectively collected national surgical outcomes database was performed to identify adult patients who underwent UKA from 2015 to 2019. Nonroutine discharge was defined as discharge to a location other than home. Five machine learning algorithms were developed to predict this outcome. Performance of the algorithms was assessed through discrimination, calibration, and decision curve analysis. Overall, of the 7275 patients included, 263 (3.6) patients were unable to return home upon discharge following UKA. The factors determined most important for identification of candidates for nonroutine discharge were total hospital length of stay, preoperative hematocrit, body mass index, preoperative sodium, American Society of Anesthesiologists classification, gender, and functional status. The extreme boosted model achieved the best performance based on discrimination (area under the curve = 0.875), calibration, and decision curve analysis. This model was integrated into a web-based open access application able to provide both predictions and explanations. The present model can, following appropriate external validation, be used to augment clinician decision-making in patients undergoing elective UKA. Patients with high preoperative probabilities of nonroutine discharge based on nonmodifiable risk factors should be counseled to start the insurance authorization process with case management to avoid unnecessary inpatient stay, and those with modifiable risk can attempt prehabilitation to optimize these parameters before surgery.


Sphingolipids and their enigmatic role in asthma.
Asthma is defined as a chronic inflammatory condition in the lung and is characterized by episodic shortness of breath with expiratory wheezing and cough. Asthma is a serious public health concern globally with an estimated incidence over 300 million. Asthma is a complex disease in that it manifests as disease of gene and environmental interactions. Sphingolipids are a unique class of lipids involved in a host of biological functions ranging from serving as key cellular membrane lipids to acting as critical signaling molecules. To date sphingolipids have been studied across various human conditions ranging from neurological disorders to cancer to infection to autoimmunity. This review will focus on the role of sphingolipids in asthma development and pathology with particular focus on the role of mast cell sphingolipid biology.


Responses of yield, quality and water use efficiency of potato grown under different drip irrigation and nitrogen levels.
Proper irrigation and fertilization are essential for achieve high tuber yield and quality in potato production. However, the high cost of these inputs necessitate optimization of their use to improve both water use efficiency and crop productivity. This study aimed to investigate the impact of irrigation and nitrogen fertilization on potato yield, quality and water use efficiency. The research included different drip irrigation treatments (100%, 66%, and 33% of field capacity) and nitrogen levels: 0 (N0), 100 (N1), 200 (N2), 300 (N3), 400 (N4) and 500 (N5) kg N ha-1. The results indicated that potato yield and growth were more sensitive to irrigation treatment than nitrogen levels. Full irrigation with 300 kg N ha-1 produced the highest total tuber yield, while low irrigation treatments resulted in significantly lower yields. In contrast, the 66% field capacity irrigation treatment consistently had the highest water use efficiency in both years of the study. Furthermore, the study showed that the quality characteristics of the tubers were negatively impacted by full irrigation treatments compared to low irrigation. These findings suggest that with appropriate irrigation and nitrogen application, potatoes can be produced with acceptable yields while conserving water and minimizing nitrogen use. This research emphasizes the importance of optimizing inputs to improve water use efficiency and yield productivity while reducing water. As a result, obtaining useful information on crop management for farmers to make informed decisions may be possible by achieving optimal irrigation and nitrogen levels.


Effect of the GABAB antagonist, phaclofen, on baclofen-induced inhibition of micturition reflex in urethane-anesthetized rats.
The effect of intrathecal or intracerebroventricular administration of the GABAB receptor agonist, baclofen, on rhythmic contractions induced by distension of the urinary bladder (micturition reflex) was evaluated in urethane-anesthetized rats. Baclofen inhibited bladder motility acting at central nervous system sites (spinal and supraspinal) with a comparable potency. The inhibitory effect of i.t. baclofen (0.1-10 nmol) was blocked by i.t. phaclofen (200 nmol) while i.c.v. phaclofen did not affect i.c.v. baclofen (0.1-1 nmol). The inhibition of the micturition reflex induced by bladder distension observed after i.t. administration of baclofen was unaffected by systemic capsaicin pretreatment (50 mg/kg s.c., four days before). On the other hand, i.t. baclofen suppressed, in a phaclofen-sensitive manner, the reflex bladder contraction evoked by chemical stimulation (topical capsaicin) of capsaicin-sensitive bladder afferents. Intrathecal baclofen did not affect the hexamethonium-resistant tonic contraction produced by topical application of capsaicin on to the urinary bladder, which is ascribable to local peptide release from sensory nerves. Bladder motility inhibition by i.t. or i.c.v. baclofen (1 nmol) was unchanged by previous administration of p-chlorophenylalanine, indicating that the serotonergic pathways do not play a role in its action. Baclofen (100 microM) suppressed the release of calcitonin gene-related peptide-like immunoreactivity evoked by electrical field stimulation from the dorsal half of the rat spinal cord. This response was also abolished by in vitro capsaicin desensitization or tetrodotoxin, indicating that baclofen suppresses transmitter release from central endings of capsaicin-sensitive primary afferents. The present findings indicate that baclofen acts at both spinal and supraspinal sites to inhibit, with different mechanisms, the micturition reflex.(ABSTRACT TRUNCATED AT 250 WORDS)


Cingulate circuits are associated with escalation of heroin use and naloxone-induced increases in heroin self-administration.
Opioid use disorder (OUD) is defined as a compulsion to seek and take opioids, loss of control over intake and the development of a negative emotional state when access to opioids is denied. Using functional magnetic resonance imaging (fMRI) data in a rat model of OUD, we demonstrate that the escalation of heroin self-administration (SA) and the increased heroin SA following an injection of an opioid receptor antagonist (naloxone) are associated with changes in distinct brain circuits, centered on the cingulate cortex (Cg). Here, SA escalation score was negatively associated with changes in resting state functional connectivity (rsFC) between the Cg and the dorsal striatum. Conversely, increased heroin SA following naloxone injection, was associated with increased connectivity between the Cg and the extended amygdala and hypothalamus. Naloxone-induced increased SA was also positively associated with changes in the amplitude of low frequency fluctuations within the Cg, a measure of spontaneous neuronal activity. Characterizing the distinct brain circuit and behavior changes associated with different facets of addiction increases our understanding of OUD and may provide insight into addiction prevention and treatment.


Fatal coastal drowning incidents: A 10-year review of body recovery times in New Zealand.
Despite drowning being a leading cause of unintentional injury worldwide, gaps in the data still exist. One area where limited data is available to guide lifeguards, police, search and rescue agencies, accident and forensic investigators, ocean scientists, and the coroner, is how far from the last known point (displacement) a missing person is likely to be found, and the time frame for this to occur. This lack of certainty can exacerbate the emotional toll on family, friends, and rescuers. This study aimed to describe body recovery times and displacement for fatal coastal drowning incidents in New Zealand. Using DrownBase™, the National Coronial Information System, and media reports, data were extracted for all fatal coastal-missing-person drowning incidents from 2008 to 2017. A total of 219 cases were selected. Almost all incidents involved males (92%) and minority groups (e.g., Māori and Pasifika) were over-represented. Older adults (> 42 years) were more likely to be engaged in boating, whereas for younger adults (≤ 42 years), it was swimming. Most missing persons were described as good swimmers (51%) and wearing everyday clothing (48%), yet only 4% wore a lifejacket. Most incidents were observed (63%), and rescue was attempted in 86% of cases. Most bodies (58%) were recovered within 24h, and only 15% were not found (9%) or not reported (6%). Most missing persons (64%) were either found in the same location (57%) or <1km from where they entered the water (7%). The quality of on-scene data limited some analysis, and the results of this study may not apply to all aquatic locations. Improved data collection could inform real-time predictive modelling of where and when a missing person might be found. The involvement of forensic and ocean scientists in future study design to widen applicability to these domains is also recommended. Fewer lives would be lost to drowning, however, if safer practices were adopted when recreating or working in, on, or around water.


Simultaneous optimization of power and duration of radio-frequency pulse in PARACEST MRI.
Chemical exchange saturation transfer (CEST) MRI is increasingly used to probe mobile proteins and microenvironment properties, and shows great promise for tumor and stroke diagnosis. The CEST effect is complex and depends not only on the CEST agent concentration, exchange rates, the characteristic of the magnetization transfer (MT), and the relaxation properties of the tissue, but also varies with the experimental conditions such as radio-frequency (RF) pulse power and duration. The RF pulse is one of the most important factors that promote the CEST effect for biological properties such as pH, temperature and protein content, especially for contrast agents with intermediate to fast exchange rates. The CEST effect is susceptible to the RF duration and power. The present study aims at determining the optimal power and the corresponding optimal duration (that maximize the CEST effect) using an off-resonance scheme through a new definition of the CEST effect. This definition is formulated by solving the Bloch-McConnell equation through the R1ρ method (based on the eigenspace solution) for both of the MT and CEST effects as well as their interactions. The proposed formulations of the optimal RF pulse power and duration are the first formulations in which the MT effect is considered. The extracted optimal RF pulse duration and power are compared with those of the MTR asymmetry model in two- and three-pool systems, using synthetic data that are similar to the muscle tissue. To validate them further, the formulations are compared with the empirical formulation of the CEST effect and other findings of the previous researches. By extending our formulations, the optimal power and the corresponding optimal duration (in the biological systems with many chemical exchange sites) can be determined.


Patient-Reported Health Outcomes After in Situ Percutaneous Fixation for Slipped Capital Femoral Epiphysis: An Average Twenty-Year Follow-up Study.
Percutaneous in situ fixation is the gold-standard treatment for stable slipped capital femoral epiphysis (SCFE). While numerous studies have documented good to excellent long-term clinical and radiographic outcomes, few have documented long-term patient-reported outcomes of patients with this condition. This retrospective study was performed to document long-term patient-reported outcomes of a cohort of sixty-four patients with SCFE (ninety-one affected hips) and determine whether the slip angle was associated with poorer health outcomes as measured with the Short Form-12 (SF-12) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, modified Harris hip score (mHHS), and University of California at Los Angeles (UCLA) Activity Scale. The mean age at presentation was 12.6 years, and the mean duration of follow-up was 19.6 years. At the time of follow-up, the cohort reported higher rates of diabetes, obesity, and hypertension than the general U.S. The mean body mass index (BMI) had increased by 10.2 kg/m(2), with 72% of the subjects meeting the criteria for obesity (BMI > 30 kg/m(2)) at the time of follow-up. The mean age and sex-adjusted PCS and MCS scores were 49.6 and 50.0, respectively, and the mean mHHS was 84.9. Multivariable general linear modeling revealed no association between the initial slip angle and the PCS, MCS, mHHS, or UCLA Activity Scale score. Male sex and a lower BMI were the only predictors of better long-term PCS, mHHS, and UCLA Activity Scale scores. Subjects with a bilateral slip had outcomes similar to those with unilateral disease. The general self-reported health of this cohort was poor compared with that of the general population. The slip angle on presentation did not correlate with any patient-reported outcome measure collected for this study. Higher BMI was one of the only clinical predictors of patient-reported outcomes.


Further observations of true mosaic trisomy 17 ascertained in amniotic fluid cell cultures.
Three new cases of true mosaic trisomy 17 (MT17) were diagnosed in amniotic fluid cells. Postnatal chromosome analysis from lymphocytes did not confirm the trisomic cell line, and follow-up studies showed normal psycho-motor development of the children, in one case up to the age of 4 1/2 years. We suggest that there are similarities between MT17 and MT20, in which the majority of pregnancies result in deliveries of healthy babies.


A Comparison Between Hyaluronic Acid and Polylactic Acid Filler Injections for Temporary Penile Augmentation in Patients with Small Penis Syndrome: A Multicenter, Patient/Evaluator-Blind, Comparative, Randomized Trial.
There are only a few studies on the clinical utility of filler injections for penile augmentation (PA) in patients with small penis syndrome (SPS), which is a type of anxiety or body dysmorphic disorder, not a true micropenis. To compare the clinical outcomes of hyaluronic acid (HA) with polylactic acid (PLA) filler injection for temporary PA in patients with SPS. Our prospective, patient/evaluator-blind, comparative, randomized, non-inferiority trial consisted of a single filler injection and a 24-week post-injection period. Seventy-four men with SPS were included between November 2017 and February 2018. Patients were divided into those injected with HA (n = 39) and those injected with PLA filler (n = 35). The psychological effects of PA, based on the Beliefs about Penis Size Scale, penile girth, and satisfaction, were assessed at baseline and at 4, 12, and 24 weeks post-injection. At 24 weeks, the mean penile girth increases were 2.1 ± 1.0 cm (P < .001) in the HA group and 1.6 ± 0.9 cm (P < .001) in the PLA group, with a mean difference of 0.5 ± 0.2 cm between groups (P = .031). In both groups, satisfaction levels significantly increased at 24 weeks, with 1.8 ± 1.7 and 1.6 ± 1.4 mean increases in the visual analog scale for penile appearance satisfaction in the HA and PLA groups, respectively (each P < .001), and 1.0 ± 1.1 and 0.7 ± 1.2 mean increases in the visual analog scale for sexual life satisfaction in the HA and PLA groups, respectively (each P < .001), with no significant differences between groups (P = .950 and P = .287). The mean Beliefs about Penis Size Scale scores significantly decreased at 24 weeks, with 7.8 ± 8.3 and 5.3 ± 7.2 mean decreases in the HA and PLA groups, respectively (each P < .001), and no significant difference between the groups (P = .920). There were no serious adverse events, but filler injection-related adverse events in the HA and the PLA groups were reported in 2 cases (5.13%) and 5 cases (14.29%), respectively (P = .245). Our study provides an overview of clinical course after HA and PLA filler injections for PA and suggests that filler injections can be considered an alternative approach in patients with SPS. Our study is the first to assess the psychological symptoms in patients with SPS who received the filler injection for PA; however, the follow-up duration was insufficient to prove the long-term outcomes of fillers. Without serious adverse events, HA and PLA filler injections for PA significantly resulted in not only an augmentative effect but also improvement of psychological distress, and the clinical utility was comparable between the fillers. Yang DY, Jeong HC, Ahn ST, et al. A Comparison Between Hyaluronic Acid and Polylactic Acid Filler Injections for Temporary Penile Augmentation in Patients with Small Penis Syndrome: A Multicenter, Patient/Evaluator-Blind, Comparative, Randomized Trial. J Sex Med 2020;17:133-141.


Efficacy of doripenem in the treatment of Pseudomonas aeruginosa experimental pneumonia versus imipenem and meropenem.
The aim of this study was to compare doripenem with imipenem and meropenem in an experimental rabbit model of Pseudomonas aeruginosa pneumonia and then to compare different doripenem doses and methods of intravenous administration. Using a rabbit experimental model of pneumonia, efficacy was assessed following 2 days of treatment by colony counts of different tissues (lung, spleen and blood culture). Mean pulmonary bacterial loads were 3.17 ± 0.53, 3.42 ± 0.61 and 2.75 ± 0.59 log(10) cfu/g for imipenem, doripenem (0.5 g three times daily) and meropenem, respectively, compared with 7.57 ± 0.99 cfu/g for control animals. At a higher dose (1 g three times daily), doripenem showed significantly better efficacy (2.70 ± 0.65 log(10) cfu/g) than the standard regimen of doripenem. Sterilization of spleen cultures was achieved with standard regimens of imipenem (1 g three times daily) and a higher dose of doripenem. In this model of P. aeruginosa pneumonia, doripenem had an efficacy equivalent to that of meropenem and imipenem at a high dose of 1 g three times a day and lower efficacy at a standard dose (0.5 g three times daily) than the other two agents in terms of bacteria cultivated from spleens. Doripenem is a new drug that offers new therapeutic options, especially for difficult-to-treat infections such as pneumonia due to non-fermenting Gram-negative bacteria.


The use of steroid-sparing agents in steroid-sensitive nephrotic syndrome.
Childhood nephrotic syndrome (NS) is frequently characterized by a relapsing course. There is no uniform agreement about the precise stage at which a steroid-sparing agent should be introduced to control the disease. In order to evaluate the treatment strategies and outcome of steroid-sensitive NS over the last 2 decades, a retrospective notes review was undertaken in a cohort of children treated at Great Ormond Street Children's Hospital between 1980 and 2000. From a population of 863 children with NS referred, 509 had frequently relapsing or steroid-dependent disease and 261 children received at least one steroid-sparing agent. Cyclophosphamide was the first choice in 178 patients and in 114 no further steroid-sparing agent was needed. Levamisole was prescribed as the first steroid-sparing agent for 65 children and disease control was achieved in 30%. Cyclosporin A was prescribed in 61 children and sustained remission was induced in 69%. It is concluded that cyclophosphamide is a potent agent in inducing sustained remission in steroid-sensitive NS. Levamisole and cyclosporin A have emerged as attractive steroid-sparing agents. Complications and major side effects of treatment are infrequent but occasionally fatal.


Norepinephrine in Goal-Directed Fluid Therapy During General Anesthesia in Elderly Patients Undergoing Spinal Operation: Determining Effective Infusion Rate to Enhance Postoperative Functions.
Intraoperative hypotension is a common complication in general anesthesia that could result in different serious complications particularly in elderly patients. This Randomized Clinical Trial (RCT) aims to determine effective continuous infusion rate of norepinephrine to prevent intraoperative hypotension during spinal surgery under general anesthesia in elderly patients. This RCT was conducted on elderly patients (n= 108) undergoing general anesthesia for posterior lumbar spinal fusion. The patients were randomly divided into 0.030, 0.060, and 0.090 μg.kg-1.min-1 groups of norepinephrine infusion rates. The outcomes were assessed at entrance to operation room (T0), 15 mins after anesthesia induction (T1), 60 mins following surgery (T2), and immediately after surgery (T3). The intraoperative and postoperative complications and rehabilitation outcomes were comparatively assessed. All three groups significantly reduced the incidence of delayed wound healing (0.030 vs. 0.060 vs. 0.090 μg.kg-1.min-1; 33.3% vs. 10% vs. 10%, P=0.024) and wound infection (26.7% vs. 6.7% vs. 6.7%, P=0.031). Intraoperative total fluid volume and colloids volume in the 0.030 group were significantly higher than 0.060 and 0.090 groups (P=0.005, P=0.003, and P=0.01, respectively). The 0.060 and 0.090 groups significantly increased mean-arterial-pressure than the 0.030 group at T2 and T3. Both 0.060 and 0.090 infusion rates significantly reduced intraoperative hypotension than 0.030 dosage (P=0.01 and P=0.003, respectively). The bradycardia incidence in the 0.090 group was significantly higher than the 0.030 (P=0.026) and 0.060 groups (P=0.038). The 0.060 group decreased the first intake by 1.4 hours (P=0.008) and first flatus by 1.1 hours (P=0.004) and postoperative hospital stay by 1 day (P=0.066). The 0.060 µg·kg-1·min-1 norepinephrine infusion combined with goal-directed fluid therapy exhibited adequate intraoperative management and postoperative outcomes. www.chictr.org.cn, identifier ChiCTR-1900021309.


This is a rare case report in an elective orthopaedic setting, in which a 72-year-old man without known urologic disorders presented with a 6.2 l post-void residual urine (PVR) before a planned knee arthroplasty surgery. The PVR was found because of a newly established local guideline in an orthopaedic department regarding examination and treatment for PVR. The guideline was made in collaboration with urologists to improve the quality of treatment. Early diagnosis and treatment may prevent chronic bladder injury, urinary tract infections, urosepsis and kidney damage.


Optimization of a methodology for the determination of organochlorine pesticides in surface water by SPME-GC/MS.
In the present work experimental conditions were optimized for the analysis of organochlorine traces in water matrix using solid-phase microextraction (SPME) followed by gas chromatography with mass selective detector. The parameters including time of exposure of the fiber in the aqueous sample, fiber type, agitation speed, pH, ionic forces, temperature of adsorption, and time of desorption were evaluated. The best conditions to analyze organochlorine were obtained by using higher than room temperature, agitation of the sample, extraction time of 40 min, and polyacrylate fiber.


Mammography and the risk of thyroid cancer.
The purpose of this article is to discuss recent media reports that have suggested a link between mammography and increased incidence of thyroid cancer in women. Those reports have caused many requests that a thyroid shield be used during mammography. On the basis of a previously published study that investigated organ doses from mammography and of cancer risk estimates using the seventh Biologic Effects of Ionizing Radiation report, we contend that thyroid shielding during mammography is unnecessary and may increase retakes rather than afford radiation protection of the thyroid.


Comparison of the phenotypic characteristics between responders and non-responders to obstructive sleep apnea treatment using mandibular advancement devices in adult patients: Systematic review and meta-analysis.
Mandibular advancement device (MAD) therapy is the most commonly used second-line treatment for obstructive sleep apnea (OSA), but MAD may be ineffective in a subgroup of patients. The aim of this systematic review is to identify predictors of the efficacy of oral appliance (OA) therapy for OSA in adult patients. This review focuses on performing the quantitative analysis by subgroups based on the response criteria used in the literature and based on the type of device. PubMed, EMBASE, Scopus, Web of Science and Cochrane databases was conducted to identify potentially relevant studies published until Dec 2021. The search identified 1343 preliminary references. A total of 99 studies met the eligibility criteria and were included in the review, and 60 in the meta-analysis. The quality of studies was assessed using the Newcastle-Ottawa scale and the Cochrane scale. Based on meta-analysis, and considering a low to moderate evidence profile according to the GRADE scale, responders are younger patients, with smaller neck circumference, lower body mass index. Responders have shorter maxillary length, lower anterior and posterior facial height, a shorter distance from the hyoid bone to the third cervical vertebra, a shorter airway length, a smaller minimum airway cross-sectional area and a higher minimum oxygen saturation during sleep. Responders needed a lower optimal continuous positive airway pressure than non-responders. The type of device has not affected the results of the meta-analysis. The criterion "AHI <10 and reduction AHI >50%" is the one that provides the "weight" of significance for several variables. This criterion should be taken into consideration for future studies to predict OSA treatment by OA.


The Role of Perspective Taking on Attention: A Review of the Special Issue on the Reflexive Attentional Shift Phenomenon.
Attention is a process that alters how cognitive resources are allocated, and it allows individuals to efficiently process information at the attended location. The presence of visual or auditory cues in the environment can direct the focus of attention toward certain stimuli even if the cued stimuli are not the individual's primary target. Samson et al. demonstrated that seeing another person in the scene (i.e., a person-like cue) caused a delay in responding to target stimuli not visible to that person: "alter-centric intrusion." This phenomenon, they argue, is dependent upon the fact that the cue used resembled a person as opposed to a more generic directional indicator. The characteristics of the cue are the core of the debate of this special issue. Some maintain that the perceptual-directional characteristics of the cue are sufficient to generate the bias while others argue that the cuing is stronger when the cue has social characteristics (relates to what another individual can perceive). The research contained in this issue confirms that human attention is biased by the presence of a directional cue. We discuss and compare the different studies. The pattern that emerges seems to suggest that the social relevance of the cue is necessary in some contexts but not in others, depending on the cognitive demand of the experimental task. One possibility is that the social mechanisms are involved in perspective taking when the task is cognitively demanding, while they may not play a role in automatic attention allocation.


Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
The glycan structures of the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells have been studied by using NMR. The different possible interacting epitopes have been deeply analysed and characterized, providing evidence of the presence of glycan structures not found in previous MS-based analyses. The interaction of the RBD 13 C-labelled glycans with different human lectins, which are expressed in different organs and tissues that may be affected during the infection process, has also been evaluated by NMR. In particular, 15 N-labelled galectins (galectins-3, -7 and -8 N-terminal), Siglecs (Siglec-8, Siglec-10), and C-type lectins (DC-SIGN, MGL) have been employed. Complementary experiments from the glycoprotein perspective or from the lectin's point of view have permitted to disentangle the specific interacting epitopes in each case. Based on these findings, 3D models of the interacting complexes have been proposed.


Fixation artefact in an intra-operative frozen section: a potential cause of misinterpretation.
The intra-operative histological assessment of fresh tissue can provide valuable diagnostic information and guide surgical management, however, even a limited exposure to standard fixation agents can potentially compromise analysis. Defined handling strategies should exist to facilitate the receipt of all specimens, in their optimal state, by the laboratory.


NA1-115-7, from Zygogynum pancheri, is a new selective MCL-1 inhibitor inducing the apoptosis of hematological cancer cells but non-toxic to normal blood cells or cardiomyocytes.
The overexpression of antiapoptotic members (BCL-2, BCL-xL, MCL-1, etc.) of the BCL-2 family contributes to tumor development and resistance to chemotherapy or radiotherapy. Synthetic inhibitors targeting these proteins have been developed, and some hematological malignancies are now widely treated with a BCL-2 inhibitor (venetoclax). However, acquired resistance to venetoclax or chemotherapy drugs due to an upregulation of MCL-1 has been observed, rendering MCL-1 an attractive new target for treatment. Six MCL-1 inhibitors (S64315, AZD-5991, AMG-176, AMG-397, ABBV-467 and PRT1419) have been evaluated in clinical trials since 2016, but some were affected by safety issues and none are currently used clinically. There is, therefore, still a need for alternative molecules. We previously described two drimane derivatives as the first covalent BH3 mimetics targeting MCL-1. Here, we described the characterization and biological efficacy of one of these compounds (NA1-115-7), isolated from Zygogynum pancheri, a plant belonging to the Winteraceae family. NA1-115-7 specifically induced the apoptosis of MCL-1-dependent tumor cells, with two hours of treatment sufficient to trigger cell death. The treatment of lymphoma cells with NA1-115-7 stabilized MCL-1, disrupted its interactions with BAK, and rapidly induced apoptosis through a BAK- and BAX-mediated process. Importantly, a similar treatment with NA1-115-7 was not toxic to erythrocytes, peripheral blood mononuclear cells, platelets, or cardiomyocytes. These results highlight the potential of natural products for use as specific BH3 mimetics non-toxic to normal cells, and they suggest that NA1-115-7 may be a promising tool for use in cancer treatment.


A rational approach to total thymectomy in the treatment of myasthenia gravis.
Thymectomy is important in the treatment of myasthenia gravis. Total removal of the gland is considered indicated. Although median sternotomy has been the accepted surgical procedure, the transcervical approach has been advocated as a safer method of achieving total thymectomy. A surgical-anatomical study of the thymus was made in 22 patients. A high incidence of surgically important variations in thymic anatomy was found in the neck and in the mediastinum. We believe wide exposure by way of median sternotomy with direct vision is required to remove all of the extracapsular mediastinal thymus in many patients, and good cervical exposure is required to remove the anomalous tissue in the neck. If a total thymectomy is to be achieved, we recommend a median sternotomy and a cervical incision, using the meticulous dissection described.


Identification of a novel mutation of NOG in family with proximal symphalangism and early genetic counseling.
Proximal symphalangism is a rare disease with multiple phenotypes including reduced proximal interphalangeal joint space, symphalangism of the 4th and/or 5th finger, as well as hearing loss. At present, at least two types of proximal symphalangism have been identified in the clinic. One is proximal symphalangism-1A (SYM1A), which is caused by genetic variants in Noggin (NOG), another is proximal symphalangism-1B (SYM1B), which is resulted from Growth Differentiation Factor 5 (GDF5) mutations. Here, we reported a Chinese family with symphalangism of the 4th and/or 5th finger and moderate deafness. The proband was a 13-year-old girl with normal intelligence but symphalangism of the 4th finger in the left hand and moderate deafness. Hearing testing and inner ear CT scan suggested that the proband suffered from structural deafness. Family history investigation found that her father (II-3) and grandmother (I-2) also suffered from hearing loss and symphalangism. Target sequencing identified a novel heterozygous NOG mutation, c.690C > G/p.C230W, which was the genetic lesion of the affected family. Bioinformatics analysis and public databases filtering further confirmed the pathogenicity of the novel mutation. Furthermore, we assisted the family to deliver a baby girl who did not carry the mutation by genetic counseling and prenatal diagnosis using amniotic fluid DNA sequencing. In this study, we identified a novel NOG mutation (c.690C > G/p.C230W) by target sequencing and helped the family to deliver a baby who did not carry the mutation. Our study expanded the spectrum of NOG mutations and contributed to genetic diagnosis and counseling of families with SYM1A.


Nutritional support in surgical practice: Part II.
On admission, a group of high-risk patients who are potential candidates for surgery can be identified, in whom prompt initiation of preoperative enteral or parenteral nutrition may reduce postoperative morbidity and mortality irrespective of the nutritional status. Among these are patients with inflammatory bowel disease, gastrointestinal fistulas, and pancreatitis. Substantial nutritional support has little or no direct effect upon the pathogenesis of the disease, but the discontinuance of oral intake may well have a beneficial effect on the basic disease process. Thus, the provision of enteral or parenteral nutrition gives the patient an optimal opportunity to marshal host defenses in support of healing. In organ system failures, e.g., acute renal failure, liver failure, and pulmonary failure, appropriate nutritional support may assist the patient in coping with the abnormal intermediary metabolism resulting from such failure until satisfactory organ system function returns. From this review, it seems reasonably clear that the initially malnourished patient is less able to successfully withstand the adverse effects of vigorous therapy and/or severe illness than is the well-nourished individual. Hence, correction of malnutrition, either before initiating therapy or concomitant with the treatment, is very likely to be beneficial.


Percutaneous absorption of 1,3-bis (2-chloroethyl)-I-nitrosourea (BCNU, carmustine) in mycosis fungoides.
The total percutaneous absorption of 1,3-bis(2-chloroethyl)-I-nitrosourea (BCNU, carmustine) in 5 patients with mycosis fungoides, based on the 5 day urinary excretion of 14C-labelled BCNU, ranged from 5 to 28%. Absorption through diseased skin was greater than through uninvolved skin.


The role of cryptocurrencies in predicting oil prices pre and during COVID-19 pandemic using machine learning.
This study aims to explore the role of cryptocurrencies and the US dollar in predicting oil prices pre and during COVID-19 pandemic. The study uses three neural network models (i.e., Support vector machines, Multilayer Perceptron Neural Networks and Generalized regression neural networks (GRNN)) over the period from January 1, 2018, to July 5, 2021. Our results are threefold. First, our results indicate Bitcoin is the most influential in predicting oil prices during the bear and bull oil market before COVID-19 and during the downtrend during COVID-19. Second, COVID-19 variables became the most influential during the uptrend, especially the number of death cases. Third, our results also suggest that the most accurate model to predict the price of oil under the conditions of uncertainty that prevailed in the world during the bear and bull prices in the wake of COVID-19 is GRNN. Though the best prediction model under normal conditions before COVID-19 during an uptrend is SVM and during a downtrend is GRNN. Our results provide crucial evidence for investors, academics and policymakers, especially during global uncertainties.


Transcatheter Aortic Valve Implantation (core valve) prosthesis complicated by mitral stenosis.
A 90 year-old male patient, known to have severe aortic stenosis (AS), was admitted with chest pain, shortness of breath and swelling of both lower limbs. He had history of ischemic heart disease and percutaneous coronary intervention (PCI) of left anterior descending artery (LAD) in 2002. He also had long standing hypertension, primary hypothyroidism and hypercalcemia. He had a permanent pacemaker, chronic gastritis, gastrointestinal bleeding and bilateral knee osteoarthritis in 2007. Patient was treated medically for his heart failure symptoms. Transthoracic echocardiogram (TTE) showed normal ejection fraction >55% and severe aortic stenosis, aortic valve area 0.58 cm(2), mean G 64 mmHg and peak gradient of 118 mm Hg. In November 2010 the patient was evaluated for the transcatheter aortic valve implantation (TAVI) program after a multidisciplinary evaluation. His predicted Euro Score was 28% and both risk and benefits were explained to the family. A 29 mm core valve prosthesis was deployed. The TTE 4 days later showed mitral valve (MV) area = 2.04 cm(2) and MG across MV = 6 mm Hg. Impingement of anterior mitral valve leaflet (AMVL) by the inflow portion of core valve prosthesis led to mild mitral stenosis (MS). TEE is a helpful tool to diagnose this phenomenon.


Antral follicle count as a predictor of ovarian responsiveness in women with endometriomas or with a history of surgery for endometriomas.
To evaluate the accuracy of antral follicular count (AFC) in predicting ovarian responsiveness in ovaries with endometriomas or with a past history of surgical excision of endometriomas. Retrospective review. Academic hospital. Eighty-three women for a total of 166 gonads. None. Total number of developing follicles. The ovaries were characterized as four groups: [1] unoperated gonads without endometriomas (n = 42, control group), [2] unoperated gonads with endometriomas (n = 46), [3] operated gonads without endometriomas (n = 55), and [4] operated gonads with endometriomas (n = 23). The analyses subsequently considered all ovaries with endometriomas (groups 2 + 4, n = 69) and all operated ovaries (groups 3 + 4, n = 78). The capacity of AFC to predict low response (≤ 2 follicles) or hyperresponsiveness (≥ 7 follicles) was evaluated using receiver operating characteristic curves. We used a linear regression model to calculate the adjusted B coefficients. The adjusted B coefficients in unaffected ovaries, in all ovaries with endometriomas, and in all operated ovaries were 0.55 (95% confidence interval [CI], 0.07-1.03), 0.76 (95% CI, 0.54-0.98), and 0.51 (95% CI, 0.26-0.76), respectively. The area under the curve (AUC) for the prediction of low response was 0.83 (95% CI, 0.68-0.99), 0.83 (95% CI, 0.73-0.93), and 0.74 (95% CI, 0.63-0.85), respectively. The AUC for the prediction of hyperresponse was 0.84 (95% CI, 0.70-0.97), 0.74 (95% CI, 0.63-0.85), and 0.77 (0.60-0.94), respectively. The accuracy of AFC for predicting ovarian response is similar in unaffected ovaries, ovaries with endometriomas and ovaries with a history of surgery for endometriomas.


Drug Interactions: Classification and Systematic Approach.
Interactions between drugs may result in favorable, toxic or no clinical effects. Generally classified in terms of proposed mechanism, drug interactions may be causal to physicochemical incompatibility, pharmacokinetic or pharmacodynamic interaction(s), combinations of each. Characterized by alterations in circulating unbound (tree) drug or its principal metabolic, pharmacokinetic interactions are secondary to modification(s) in absorption, volume of distribution, metabolism or excretion. Synergism, defined as two or more drugs acting upon receptor site(s) to produce additive or superadditive effects, or antagonism, defined by a shifting of the dose-response curve to the right indicating a diminution of effect after stimulation of a receptor site are pharmacodynamic interactions occurring without demonstrable alteration in plasma levels of the drugs. This article reviews these various types and mechanisms of drug interactions.


Conserved sequences in the current strains of HIV-1 subtype A in Russia are effectively targeted by artificial RNAi in vitro.
Highly active antiretroviral therapy has greatly reduced the morbidity and mortality of AIDS. However, many of the antiretroviral drugs are toxic with long-term use, and all currently used anti-HIV agents generate drug-resistant mutants. Therefore, there is a great need for new approaches to AIDS therapy. RNAi is a powerful means of inhibiting HIV-1 production in human cells. We propose to use RNAi for gene therapy of HIV/AIDS. Previously we identified a number of new biologically active siRNAs targeting several moderately conserved regions in HIV-1 transcripts. Here we analyze the heterogeneity of nucleotide sequences in three RNAi targets in sequences encoding the reverse transcriptase and integrase domains of current isolates of HIV-1 subtype A in Russia. These data were used to generate genetic constructs expressing short hairpin RNAs 28-30-bp in length that could be processed in cells into siRNAs. After transfection of the constructs we observed siRNAs that efficiently attacked the selected targets. We expect that targeting several viral genes important for HIV-1 reproduction will help overcome the problem of viral adaptation and will prevent the appearance of RNAi escape mutants in current virus strains, an important feature of gene therapy of HIV/AIDS.


The orthographic sensitivity to written Chinese in the occipital-temporal cortex.
Previous studies have identified an area in the left lateral fusiform cortex that is highly responsive to written words and has been named the visual word form area (VWFA). However, there is disagreement on the specific functional role of this area in word recognition. Chinese characters, which are dramatically different from Roman alphabets in the visual form and in the form to phonological mapping, provide a unique opportunity to investigate the properties of the VWFA. Specifically, to clarify the orthographic sensitivity in the mid-fusiform cortex, we compared fMRI response amplitudes (Exp. 1) as well as the spatial patterns of response across multiple voxels (Exp. 2) between Chinese characters and stimuli derived from Chinese characters with different orthographic properties. The fMRI response amplitude results suggest the existence of orthographic sensitivity in the VWFA. The results from multi-voxel pattern analysis indicate that spatial distribution of the responses across voxels in the occipitotemporal cortex contained discriminative information between the different types of character-related stimuli. These results together suggest that the orthographic rules are likely represented in a distributed neural network with the VWFA containing the most specific information regarding a stimulus' orthographic regularity.


Towards the development of an oral vaccine against porcine cysticercosis: expression of the protective HP6/TSOL18 antigen in transgenic carrots cells.
The Taenia solium HP6/TSOL18 antigen was produced in carrot cells, yielding an immunogenic protein that induced significant protection in an experimental murine model against T. crassiceps cysticercosis when orally administered. This result supports the potential of HP6/TSOL18-carrot as a low-cost anti-cysticercosis vaccine candidate. Cysticercosis is a zoonosis caused by Taenia solium that can be prevented by interrupting the parasite life cycle through pig vaccination. Several injectable vaccine candidates have been reported, but the logistic difficulties and costs for its application limited its use in nationwide control programs. Oral plant-based vaccines can deal with this limitation, because of their easy administration and low cost. A stable expression of the HP6/TSOL18 anti-T. solium cysticercosis protective antigen in carrot calli transformed with an optimized transgene is herein reported. An antigen accumulation up to 14 µg g(-1) of dry-weight biomass was achieved in the generated carrot lines. Mouse immunization with one of the transformed calli induced both specific IgG and IgA anti-HP6/TSOL18 antibodies. A statistically significant reduction in the expected number of T. crassiceps cysticerci was observed in mice orally immunized with carrot-made HP6/TSOL18, in a similar extent to that obtained by subcutaneous immunization with recombinant HP6/TSOL18 protein. In this study, a new oral plant-made version of the HP6/TSOL18 anti-cysticercosis vaccine is reported. The vaccine candidate should be further tested against porcine cysticercosis.


The effect of physiological levels of non-esterified fatty acids on the radioimmunoassay of prostaglandins.
Non-esterified fatty acids (NEFA) can significantly interfere with the radioimmunoassay of PGE and PGF2alpha using commercially available anti-sera. PGB1 antigen-antibody binding is 50% inhibited by 110 pg of PGB1, 48 ng of PGE1, 3.5 microgram of PGF2alpha, or 9.0 microgram linoleic, 14 microgram arachidonic, 22 microgram delta-linoleic, 40 microgram palmitoleic or 45 microgram oleic acids. PGF2alpha antigen-antibody binding is 50% inhibited by 270 pg of PGF2alpha, 70 ng of PGE1, or 4.2 microgram arachidonic, 14 microgram delta-linoleic, 22 microgram linoleic, 70 microgram palmitoleic or 110 microgram oleic acids. Physiological levels of NEFA, such as the quantities found in small volumes of plasma, are sufficient to prohibit accurate prostaglandin measurements. Chromatography on small columns of silicic acid proved to be an effective technique for separation of NEFA and prostaglandin from lipid extracts, however, the results of this study suggest that the interference produced by the presence of NEFA in the measurement of prostaglandin from certain physiological fluids may be avoided if the prostaglandins are not extracted prior to radioimmunoassay.


The influence of silybin from Silybum marianum (L.) Gaertn. on in vitro phosphatidyl choline biosynthesis in rat livers.
In rat livers, removed 60 min after i.p. application of 150.6 mg/kg silybin-dihemisuccinate-di-Na-salt, in vitro incorporation of choline-(methyl-14C) into phosphatidyl choline by the postmitochondrial fraction of liver homogenates was enhanced in comparison with controls. These results are associated with increased activities of CTP-choline-phosphate cytidyltransferase. Enzyme activities were also enhanced after addition of 7.5 x 10(-6) mol/l silybin to incubation mixtures obtained from untreated rats.


Genome-wide identification and expression analysis of the Auxin-Response factor (ARF) gene family in Medicago sativa under abiotic stress.
Alfalfa (Medicago sativa) is the most widely planted legume forage and one of the most economically valuable crops in the world. The periodic changes in its growth and development and abiotic stress determine its yield and economic benefits. Auxin controls many aspects of alfalfa growth by regulating gene expression, including organ differentiation and stress response. Auxin response factors (ARF) are transcription factors that play an essential role in auxin signal transduction and regulate the expression of auxin-responsive genes. However, the function of ARF transcription factors is unclear in autotetraploid-cultivated alfalfa. A total of 81 ARF were identified in the alfalfa genome in this study. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed, identifying that ARF genes are mainly involved in transcriptional regulation and plant hormone signal transduction pathways. Phylogenetic analysis showed that MsARF was divided into four clades: I, II, III, and IV, each containing 52, 13, 7, and 9 genes, respectively. The promoter region of the MsARF gene contained stress-related elements, such as ABRE, TC-rich repeats, MBS, LTR. Proteins encoded by 50 ARF genes were localized in the nucleus without guide peptides, signal peptides, or transmembrane structures, indicating that most MsARF genes are not secreted or transported but only function in the nucleus. Protein structure analysis revealed that the secondary and tertiary structures of the 81 MsARF genes varied. Chromosomal localization analysis showed 81 MsARF genes were unevenly distributed on 25 chromosomes, with the highest distribution on chromosome 5. Furthermore, 14 segmental duplications and two sets of tandem repeats were identified. Expression analysis indicated that the MsARF was differentially expressed in different tissues and under various abiotic stressors. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis showed that the expression profiles of 23 MsARF genes were specific to abiotic stresses such as drought, salt, high temperature, and low temperature, as well as tissue-specific and closely related to the duration of stress. This study identified MsARF in the cultivated alfalfa genome based on the autotetraploid level, which GO, KEGG analysis, phylogenetic analysis, sequence characteristics, and expression pattern analysis further confirmed. Together, these findings provide clues for further investigation of MsARF functional verification and molecular breeding of alfalfa. This study provides a novel approach to systematically identify and characterize ARF transcription factors in autotetraploid cultivated alfalfa, revealing 23 MsARF genes significantly involved in response to various stresses.


Intraperitoneal recombinant interferon-alpha 2b for recurrent malignant ascites due to ovarian cancer.
Thirteen patients with malignant ascites due to recurrent ovarian cancer were treated with intraperitoneal interferon 2b (5 mu/m2 escalating to 15 mu/m2, administered twice weekly by indwelling intraperitoneal catheter). The study population included eight patients with ascites only and five patients with ascites plus tumor masses greater than 2 cm in diameter. Five of 13 responded to treatment. All the responses were seen in patients with ascites only. Although tumor mass was an important determinant of response there was also a correlation between clinical response and suppression of colony growth on soft agar after in vitro exposure of tumor cells to interferon-alpha (IFN alpha). The intraperitoneal use of IFN alpha should be explored further in tumors with a predominant intraperitoneal location and microimplantation growth pattern.


Malignant and Nonmalignant Sinonasal Tumors.
Sinonasal tumors are rare, diverse, complex lesions with overlapping demographic and clinical features. Malignant tumors are more common, with a grave prognosis, and require biopsy for accurate diagnosis. This article briefly reviews the classification of sinonasal tumors and provides imaging examples and imaging characteristics of each clinically important nasal and paranasal mass lesions. Although there are no true pathognomonic imaging features, it is important for the radiologist to have a broad knowledge of the various CT and MR imaging findings that can help narrow the differential diagnosis and aid in early diagnosis and mapping of tumor for treatment planning.


Metastatic uterine leiomyosarcoma in association with recurrent lung abscess.
A case of metastatic uterine leiomyosarcoma complicated by recurrent lung abscesses is described.


Evolution of Pediatric Critical Care Nursing.
Pediatric critical care nursing is a key pillar in patient care and outcomes for children who are ill and injured. Tremendous advances have occurred in pediatric critical care and nursing. This article provides an overview of the key advances in pediatric critical care nursing through the decades.


Anaerobic digestion of food waste for volatile fatty acids (VFAs) production with different types of inoculum: effect of pH.
Food waste anaerobic fermentation was carried out under acidic conditions using inocula based on aerobic activated sludge (Inoculum AE) or anaerobic activated sludge (Inoculum AN) for volatile fatty acids (VFAs) production. The results showed that food waste hydrolysis increased obviously when Inoculum AN was used relative to Inoculum AE at any pH investigated. Hydrolysis at pH 4.0 and uncontrolled pH was higher than that at other pHs when either inoculum was used. Additionally, VFAs production at pH 6.0 was the highest, regardless of the inoculum used. The optimum VFA yields were 0.482g/gVSSremoval with Inoculum AE and 0.918g/gVSSremoval with Inoculum AN, which were observed after 4d and 20d of fermentation, respectively. VFAs composition analysis showed that butyrate acid was the prevalent acid at pH 6.0, followed by acetate acid and propionic acid.


Subclinical protein malnutrition is a determinant of hyperhomocysteinemia.
Hyperhomocysteinemia is regarded as a public health problem of increasing importance likely to contribute to vascular disorders and premature mortality. Folate, cobalamin, pyridoxine, and riboflavin dietary deficiencies are currently regarded as causative factors. However, several investigations have indicated that the theory of vitamin B deprivation provides only a partial explanation for the observed abnormalities of sulfur-containing amino acids. We investigated the potential contributory role played by protein malnutrition. For that purpose, three cohorts of 20 adult patients presenting stage I, II, and III goiter underwent careful medical history, dietary inquiry, and clinical examination. Their overall health and nutrition states were assessed with classic anthropometry, measurement of vitamin B blood parameters, visceral protein markers, essential amino acids, total homocysteine, and cystathionine. The concentrations of transthyretin, seven essential amino acids, and cystathionine progressively decreased as the thyroid gland increased. Methionine was the sole essential amino acid whose values did not change; total homocysteine was unique in that increased levels correlated negatively with transthyretin values. Taken together, the data point to a progressive deterioration of protein nutrition status impairing the transsulfuration pathway and is best explained by an acquired defect of cystathionine-beta-synthase activity. Hyperhomocysteinemia may arise from the shrinking of endogenous nitrogen pools as a result of decreased protein intake or stress-induced increased losses. Raised total homocysteine may result from the attempt of the malnourished and/or stressed body to preserve methionine homeostasis.


Prenatal diagnosis of terminal myelocystocele in the fetal surgery era: case report.
We report a case of a child with terminal myelocystocele (TMC). This case exemplifies the importance of performing a multidisciplinary evaluation and magnetic resonance imaging in the patient with suspected meningomyelocele when fetal surgery is being considered. This patient was evaluated at the Center for Fetal Diagnosis and Treatment and considered for fetal surgery to repair meningomyelocele. A follow-up based on both ultrasound and magnetic resonance imaging was performed throughout pregnancy. Although a definitive diagnosis of TMC was not established prenatally, the patient was not offered fetal surgery, based on multiple selection criteria. We correlate the pathophysiology of TMC with the radiographic and amniocentesis findings. TMC must be considered in the differential diagnosis in a fetus with a dysraphic defect.


Aging variabilities of level-dose relationship in antiepileptic monopharmacy--with reference to drug interaction between mono- and bipharmacy.
The influences of age, dose and comedication on the dose-level relationship were investigated using the ratio of plasma level to dose per body weight (microgram/ml/mg/kg/day) as an index in patients who had received the therapeutic doses of antiepileptic drug(s) for a long term. Samples of the blood concentrations were taken from 1,922 patients ranging in age from one to 40: 1,567 measured values were obtained under medication with phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ) or valproate (VPA) alone, and 2,201 under medication with any two of the above-mentioned antiepileptic drugs. With regard to PB, PHT, CBZ and VPA, when used alone, the L/D ratio was the lowest in the youngest age group, increased toward the latter half of teens, reached a peak at about age 20 and slightly decreased in the rest between the 20s and 30s. The age when the L/D ratio changes with aging is consistent with the age when the body weight of children obviously increases. As a result, during such a term, the fairly constant blood concentration can be maintained without overtly changing the daily dose. In the same age group given a single antiepileptic drug, the L/D ratio for PHT steeply increased at the dose of 4 in adults or 5 mg/kg/day in children, while the ratio rather decreased for CBZ and VPA. Clinical considerations should be paid to the fact that there was a non-linear relationship between the dose and the plasma concentration not only of PHT but of CBZ and VPA, and that the turning points were all within the range of therapeutic doses.(ABSTRACT TRUNCATED AT 250 WORDS)


High-resolution diffusion-weighted imaging at 7 Tesla: Single-shot readout trajectories and their impact on signal-to-noise ratio, spatial resolution and accuracy.
Diffusion MRI (dMRI) is a valuable imaging technique to study the connectivity and microstructure of the brain in vivo. However, the resolution of dMRI is limited by the low signal-to-noise ratio (SNR) of this technique. Various multi-shot acquisition strategies have been developed to achieve sub-millimeter resolution, but they require long scan times which can be restricting for patient scans. Alternatively, the SNR of single-shot acquisitions can be increased by using a spiral readout trajectory to minimize the sequence echo time. Imaging at ultra-high fields (UHF) could further increase the SNR of single-shot dMRI; however, the shorter T2* of brain tissue and the greater field non-uniformities at UHFs will degrade image quality, causing image blurring, distortions, and signal loss. In this study, we investigated the trade-off between the SNR and resolution of different k-space trajectories, including echo planar imaging (EPI), partial Fourier EPI, and spiral trajectories, over a range of dMRI resolutions at 7T. The effective resolution, spatial specificity and sharpening effect were measured from the point spread function (PSF) of the simulated diffusion sequences for a nominal resolution range of 0.6-1.8 mm. In-vivo partial brain scans at a nominal resolution of 1.5 mm isotropic were acquired using the three readout trajectories to validate the simulation results. Field probes were used to measure dynamic magnetic fields offline up to the 3rd order of spherical harmonics. Image reconstruction was performed using static ΔB0 field maps and the measured trajectories to correct image distortions and artifacts, leaving T2* effects as the primary source of blurring. The effective resolution was examined in fractional anisotropy (FA) maps calculated from a multi-shell dataset with b-values of 300, 1000, and 2000 s/mm2 in 5, 16, and 48 directions, respectively. In-vivo scans at nominal resolutions of 1, 1.2, and 1.5 mm were acquired and the SNR of the different trajectories calculated using the multiple replica method to investigate the SNR. Finally, in-vivo whole brain scans with an effective resolution of 1.5 mm isotropic were acquired to explore the SNR and efficiency of different trajectories at a matching effective resolution. FA and intra-cellular volume fraction (ICVF) maps calculated using neurite orientation dispersion and density imaging (NODDI) were used for the comparison. The simulations and in vivo imaging results showed that for matching nominal resolutions, EPI trajectories had the highest specificity and effective resolution with maximum image sharpening effect. However, spirals have a significantly higher SNR, in particular at higher resolutions and even when the effective image resolutions are matched. Overall, this work shows that the higher SNR of single-shot spiral trajectories at 7T allows us to achieve higher effective resolutions compared to EPI and PF-EPI to map the microstructure and connectivity of small brain structures.


A proprotein convertase subtilisin/kexin type 9 inhibitor provides comparable efficacy with lower detriment than statins on mitochondria of oxidative muscle of obese estrogen-deprived rats.
The aim of the study was to compare the effects of atorvastatin, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i), and 17β-estradiol on oxidative muscle mitochondria in a model of menopause with obesity. Female Wistar rats consumed either a standard diet (n = 12) or a high-fat/calorie diet (HFCD: n = 60). At week 13, standard diet-fed rats underwent a sham operation, whereas HFCD-fed rats underwent either a sham operation (n = 12) or an ovariectomy (n = 48). At week 19, all sham-operated rats received vehicle, and ovariectomized HFCD-fed rats received either vehicle, 40 mg/kg/d of atorvastatin, 4 mg/kg/d of PCSK9i (SBC-115076), or 50 μg/kg/d of 17β-estradiol for 3 weeks (n = 12/group). Metabolic parameters and soleus muscle physiology were investigated at the end of week 21. Sham-operated and ovariectomized HFCD-fed rats developed obesity, hyperlipidemia, and insulin resistance, also showing increased oxidative phosphorylation (OXPHOS) proteins, ratio of p-Drp1-to-total Drp1 protein, malondialdehyde level, mitochondrial reactive oxygen species, and mitochondrial membrane depolarization in soleus muscle. All drugs equally decreased insulin resistance, OXPHOS proteins, ratio of p-Drp1-to-total Drp1 protein, and malondialdehyde level in soleus muscle. Only atorvastatin and PCSK9i attenuated hypertriglyceridemia, whereas 17β-estradiol had greater efficacy in preventing weight gain than the other two drugs. In addition, 17β-estradiol decreased mitochondrial reactive oxygen species and mitochondrial membrane depolarization. Atorvastatin increased ratio of cleaved caspase 3,8-to-procaspase 3,8, and cytochrome C. 17β-Estradiol exhibits the greatest efficacy on the attenuation of obesity with the least harmful effect on skeletal muscle in a model of menopause with obesity, yet its effect on the treatment of hyperlipidemia is inferior to those of standard lipid-lowering agents.


Organization and nucleotide sequence of the genes for ribosomal protein S2 and elongation factor Ts in Spirulina platensis.
A 6.5 kb region from the genome of the cyanobacterium Spirulina platensis was cloned using as a probe the Escherichia coli gene for ribosomal protein S2. Sequence analysis revealed, in this region, the presence of the gene for ribosomal protein S2 and part of the gene for the elongation factor Ts (EF-Ts). The arrangement rpsB-spacer-tsf resembles that reported for E. coli. The deduced amino acid sequences of the platensis S2 and EF-Ts show significant homology with the E. coli counterparts.


Importance of accessible cancer care.
Accessibility is a fundamental principle of government run health systems. Despite this, many factors impair access to care including geography, language, socioeconomic status and gender. Waiting for health care is a barrier to access that can result in significant anxiety and stress, deterioration in functional status and loss of income. Prompt access to diagnosis and treatment are key requirements to improving survival and quality of life for patients with cancer. This review will focus on studies, programs and policies aimed at improving access to care, applicability to patients with lymphoma, and potential impact. There is a growing burden on health care systems due to increasing cancer incidence and escalating health expenditures. Accordingly, initiatives and programs must be evaluated for effectiveness and efficiency.


Frameshift mutations of immunomodulatory BTN2A1, BTN2A2, and BTNL3 genes in colon cancers.
The butyrophilin family genes are immunoregulatory genes with either immune stimulatory or inhibitory functions. In the present study, we analyzed three butyrophilin genes, BTN2A1 (immune-stimulatory), BTN2A2 (inhibitory), and BTNL3 (stimulatory) genes in sporadic colon cancers (CCs). By the mutation analysis, we identified the frameshift mutations of BTN2A1, BTN2A2, and BTNL3 genes in 2, 4, and 8 CCs in microsatellite instability-high (MSI-H) CCs (2.1-8.4% of MSI-H), respectively, but not the microsatellite stable (MSS) CCs. Four of 16 MSI-H CCs (25%) exhibited regional heterogeneous mutations (RHM) of BTN2A1, BTN2A2, and BTNL3 genes. In immunohistochemistry, BTNL3 expression was lost in approximately 30% of CCs, and BTN2A2 loss was minimal in CCs (around 3%) irrespective of the MSI status. Our study revered that butyrophilin family genes BTN2A1, BTN2A2, and BTNL3 harbored multiple levels of gene alterations at frameshift mutations, RHMs, and expression losses in CCs, suggesting that butyrophilin family genes could contribute to CC pathogenesis by altering immune responses.


Detection of Arcobacter spp. in the coastal environment of the Mediterranean Sea.
The occurrence of Arcobacter spp. was studied in seawater and plankton samples collected from the Straits of Messina, Italy, during an annual period of observation by using cultural and molecular techniques. A PCR assay with three pairs of primers targeting the 16S and 23S rRNA genes was used for detection and identification of Arcobacter butzleri, Arcobacter cryaerophilus, and Arcobacter skirrowii in cultures and environmental samples. Only one of the Arcobacter species, A. butzleri, was isolated from seawater and plankton samples. With some samples the A. butzleri PCR assay gave amplified products when cultures were negative. A. cryaerophilus and A. skirrowii were never detected by culture on selective agar plates; they were detected only by PCR performed directly with environmental samples. Collectively, our data suggest that culturable and nonculturable forms of Arcobacter are present in marine environments. The assay was useful for detecting Arcobacter spp. both as free forms and intimately associated with plankton. This is the first report showing both direct isolation of A. butzleri and the presence of nonculturable Arcobacter spp. in the coastal environment of the Mediterranean Sea.


Prey size, prey perishability and group foraging in a social spider.
Selection might favor group foraging and social feeding when prey are distributed in patches that do not last long enough for a solitary individual to consume more than a small fraction of them (Pulliam and Millikan 1982; Pulliam and Caraco 1984). Here we considered the foraging behavior of a social spider, Anelosimus eximius, in light of this ephemeral resource hypothesis. This species builds large webs in which members cooperate to capture a wide variety of different sizes and types of prey, many of which are very large. The capture success of this species was very high across all prey sizes, presumably due to the fact that they foraged in groups. Group consumption times in natural colonies for all prey larger than five mm were less than the time that dead insects remained on the plastic sheets that we used as artificial webs. Solitary consumption estimates, calculated from the rate at which laboratory individuals extracted insect biomass while feeding, were the same as the residence times of insects on artificial webs in the field for insects between 6 and 15 mm in length and were significantly longer than the persistence of insects on plastic sheets for all larger insects. Large prey, that contribute substantially to colony energy supplies, appeared to be ephemeral resources for these spiders that could not be consumed by a single spider in the time they were available. These factors made the food intake of one spider in a group less sensitive to scavenging by others and could act to reinforce the social system of this species.


Estimation of prednisone intake in pemphigus vulgaris patients with the use of simple laboratory methods.
Prednisone is a widely used medication in dermatology, particularly in pemphigus patients. Simple objective laboratory methods are suggested for the evaluation of prednisone intake, taking advantage of the similar chemical structure of cortisol and prednisolone. A linear correlation was found between the dose of prednisone, above 40 mg/day, free urinary prednisolone, measured with an radioimmunoassay kit for cortisol that cross-reacts with prednisolone, and 17-hydroxycorticosteroids, measured by Metcalf's method. Approximately 9% of the prednisone administered was recovered as free prednisolone and about 40% as 17-hydroxycorticosteroids. It is suggested that these simple laboratory methods constitute a useful substitute for the more costly, sophisticated methods available at present for determining levels of prednisone and prednisolone.


Cardiac refractoriness. Age-dependence in normal subjects.
The effects of age on cardiac electrophysiologic measurements were assessed in 30 subjects between the ages of 18 and 73 years and free of structural heart disease. Occult heart disease was excluded by a normal treadmill exercise tolerance test, a rest and exercise radionuclide angiogram, and/or a cardiac catheterization. Effective and functional refractory periods of right atrium, right ventricle, and atrioventricular node were assessed. The relationship between these measurements and age was examined using linear regression. There were significant correlations between age and atrial effective and functional refractory periods, atrioventricular effective refractory period, and ventricular effective and functional refractory periods. Other electrophysiologic measures showed no such relationship with age.


Herbivory tolerance of Agropyron smithii populations with different grazing histories.
The effects of defoliation on growth and nitrogen (N) nutrition were examined in populations of Agropyron smithii (western wheatgrass) collected from a heavily grazed black-tailed prairie dog (Cynomys ludovicianus) colony (ON-colony) and a nearby lightly grazed, uncolonized area (OFF-colony). Defoliated and nondefoliated plants were grown at low soil N availability with similar sized defoliated individuals of A. smithii from a grazing-exclosure population as a common competitor. Sequential harvests were made over 24 days following defoliation. Growth analysis plus biomass and N yield and distribution data were used to identify features which may contribute to plant defoliation tolerance. Defoliation reduced total production 34% across populations. Defoliated plants produced as much new blade tissue, but only 67% as much new root biomass as did nondefoliated controls. Plants from prairie dog colonies accumulated biomass at a faster relative rate than did plants from uncolonized sites, in part, because of a 250% greater mean relative growth rate of blades and more than 200% greater rate of biomass production per unit blade biomass. Total N accumulation was significantly greater in defoliated ON- than OFF-colony individuals. The mean relative accumulation rate of N was increased by defoliation in ON-colony plants, but reduced by defoliation in OFF-colony plants. The mean rate of N accumulation per unit root biomass was more than 300% greater in the ON- than OFF-colony population. Colony plants initially had a greater proportion of biomass and N remaining after defoliation in roots. Initial differences between populations in the distribution of biomass and N were eliminated as colony plants concentrated 24-day accumulation of biomass and N in aboveground structures. The data suggest that the combination of growth, N nutrition, and biomass and N distribution characteristics of the colony population likely confer a high rate of resource capture on heavily grazed prairie dog colonies.