Effect of hormone replacement therapy on atherogenic lipid profile in postmenopausal women.
Women develop cardiovascular disease (CVD) approximately 7-10 years later than men, but progress with similar risk after menopause. Recent studies suggest that hormone replacement therapy (HRT) is cardioprotective when initiated early after menopause, but the mechanisms involved are still unclear. In the current study, we aimed to examine the effects of HRT treatment on the plasma atherogenicity in postmenopausal women. We studied the total lipid profile in blood samples collected in a randomized, double-blinded, placebo controlled clinical trial of women with a history of venous thrombosis (VT), the EVTET study. One-hundred and forty postmenopausal women <70 years were included in EVTET and randomized either to active treatment (one tablet of 2 mg estradiol and 1 mg norethisterone acetate daily) (n = 71) or placebo (n = 69). Blood samples were taken at baseline and after 3 months and subjected to routine assessment of hemostatic factors and lipids. Our study show that HRT compared to placebo significantly reduced plasma levels of Lp(a), ApoA1, ApoB, total cholesterol (TC), HDL-C, LDL-C, TC/HDL-C and LDL-C/HDL-C ratio at 3 months. No effect was observed on ApoB/ApoA1 ratio or triglycerides. The change in Lp(a) was significantly and inversely correlated with the change in estradiol (r = -0.32; P = 0.001) and positively correlated to the change in lipids, tissue factor pathway inhibitor activity and antigen, protein C and fibrinogen (r between 0.26 and 0.45, p < 0.01). In sum, this study confirms a strong effect of HRT on atherogenic lipids with a large reduction in the pro-thrombotic Lp(a), suggesting an overall favorable effect on thrombogenicity after HRT replacement therapy in post-menopausal women at risk of VT.


The pretectal nucleus lentiformis mesencephali of Rana pipiens.
The pretectal nucleus lentiformis mesencephali (nLM) of Rana pipiens was investigated with autoradiographic, horseradish peroxidase (HRP), and Golgi techniques. Retinal afferents to nLM originate primarily from the central retina. The primary projection is contralateral with a small ipsilateral component. Following optic nerve transection and HRP impregnation, contralateral retinal afferents show a restricted, dense core of HRP label in the superficial portion of the nucleus with sparser HRP label in the surround. Ipsilateral retinal afferents arborize throughout nLM, except in the dense-core region. Additional afferents to nLM originate from the ipsilateral tectum, the nucleus rotundus, the mesencephalic pretectal gray, the contralateral nLM, and the nucleus of the basal optic root. Afferents from the accessory optic system arborize only in the dense-core region, following HRP injections into the nucleus of the basal optic root, while afferents from the mesencephalic pretectal gray arborize in all parts of nLM except the dense core. Afferents from the tectum and anterior thalamus appear to arborize throughout the nucleus without discernible pattern. The lamination of afferent terminals in nLM was correlated with Nissl-stained cytoarchitectural material in which the majority of large neurons cluster around the dense core of nLM. Three types of neurons occur in nLM: large neurons (25-micron dia.), fusiform neurons (12.5-micron dia.), and stellate neurons (10-micron dia.). Additionally, two cell groups outside nLM which send dendrites into the nucleus were observed: cells of the posterior lateral nucleus and cells of the posterior thalamic pretectal gray. Both large and fusiform neurons project to the deep layers of the optic tectum as well as to the ventral rhombencephalon superficial to the abducens nucleus. While a small number of fusiform neurons project to the nucleus of the basal optic root, the stellate neurons appear to be intrinsic to nLM. The anuran nLM strongly resembles the nucleus of the optic tract in mammals in terms of the site of origin of its retinal afferents, lamination of afferent terminations, its central connections, and its demonstrated involvement in horizontal optokinetic nystagmus.


Infectious disease outbreaks and increased complexity of care.
This study examined the effects of healthcare-associated infectious disease outbreaks on nurses' work in a large acute care hospital in Ontario, Canada. The incidence of healthcare-associated infections has increased. Previous research focuses on epidemiology, healthcare systems, and the economic burden of outbreaks. Few published studies focus on the impact of outbreaks on nurses' work in acute care facilities. Since the severe acute respiratory syndrome epidemic in 2003, combating infectious diseases has become a key issue. Hospitals have implemented measures related to healthcare-associated infections. However, nurses experience challenges in preventing, controlling, and contending with outbreaks. A retrospective exploratory case study approach was used. Data were collected over a 4-month period in 2012. The incidence rates of site-specific HAIs were analysed, and individual interviews were held with 23 bedside nurses and five nurse managers. Five themes emerged from the interviews: comparison of healthcare-associated infections outbreaks; the nature of nurses' work; impact of outbreaks on patient care; innovation and quality control in clinical practice; and increased and expanded IPAC measures. The incidence rates of methicillin-resistant Staphylococcus aureus, Clostridium difficile and vancomycin-resistant enterococci at the study site decreased, but remained above provincial benchmarks. Nurses experienced workload challenges, time pressures and psychological effects stemming from outbreaks and developed various innovations in response. Patient care was also affected. Nurses' work has been impacted by healthcare-associated infectious disease outbreaks. Nursing workloads should be quantified to facilitate the development of guidelines for optimum nurse-patient ratio during outbreaks. A strong evidence-based policy framework is required to address healthcare-associated infectious disease outbreaks. Infection prevention and control guidelines and procedures should be established provincially and nationally. An interdisciplinary approach is essential for the creation of comprehensive and innovative strategies. Nursing research has increased understanding of the implications of infectious diseases in hospitals. Building on the literature, findings from this study can be used to influence policies on the care of patients who have secondary infections. Nurse-driven protocols are important and can lead to the creation of best practice guidelines that can be implemented across settings.


Plants Show Us the Light.
In a recent article, Arp et al. (Science 2020, 368, 1490-1495) propose a new theory as to why plants are green: plants prioritize the management of light fluctuations over maximal efficiency. Beyond plant science, this conclusion may inspire our sustainability strategies, to shift our societal goals from performance to resilience.


Safe CRISPR-Cas9 Inhibition of HIV-1 with High Specificity and Broad-Spectrum Activity by Targeting LTR NF-κB Binding Sites.
Viral latency of human immunodeficiency virus type 1 (HIV-1) has become a major hurdle to a cure in the highly effective antiretroviral therapy (ART) era. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has successfully been demonstrated to excise or inactivate integrated HIV-1 provirus from infected cells by targeting the long terminal repeat (LTR) region. However, the guide RNAs (gRNAs) have classically avoided transcription factor binding sites (TFBSs) that are readily observed and known to be important in human promoters. Although conventionally thought unfavorable due to potential impact on human promoters, our computational pipeline identified gRNA sequences that were predicted to inactivate HIV-1 transcription by targeting the nuclear factor κB (NF-κB) binding sites (gNFKB0, gNFKB1) with a high safety profile (lack of predicted or observed human edits) and broad-spectrum activity (predicted coverage of known viral sequences). Genome-wide, unbiased identification of double strand breaks (DSBs) enabled by sequencing (GUIDE-seq) showed that the gRNAs targeting NF-κB binding sites had no detectable CRISPR-induced off-target edits in HeLa cells. 5' LTR-driven HIV-1 transcription was significantly reduced in three HIV-1 reporter cell lines. These results demonstrate a working model to specifically target well-known TFBSs in the HIV-1 LTR that are readily observed in human promoters to reduce HIV-1 transcription with a high-level safety profile and broad-spectrum activity.


Comparative evaluation of surfactant and hydrophobizing agent concentration in relation to the optimal particle size of metered-dose inhalers.
The aim of the present study was to formulate stabilized suspension-type metered-dose inhalation aerosols, and to examine the connection between the stabilizing additives and the optimal particle size. For the stabilization of the suspended particles, hydrophilic- and hydrophobic-type additives were applied. Oleil oleate was selected as a hydrophilic anionic surfactant, and the hydrophobizing agent was dimethyl siloxane polymer. The effect of the amount of the applied hydrophilic and hydrophobic additives on the optimal particle size was modeled by a second-order polynomial equation fitted to the data gathered by a face-centered central composite statistical design. We found that if the proper type and amount of additives are selected, it is possible to acquire the therapeutically best composition.


The absence of functional bassoon at cone photoreceptor ribbon synapses affects signal transmission at Off cone bipolar cell contacts in mouse retina.
Off cone bipolar cells of the mammalian retina connect to cone photoreceptor synaptic terminals via non-invaginating flat contacts at a considerable distance from the only established neurotransmitter release site so far, the synaptic ribbon. Diffusion from the ribbon synaptic active zone is considered the most likely mechanism for the neurotransmitter glutamate to reach postsynaptic receptors on the dendritic tips of Off cone bipolar cells. We used a mutant mouse with functionally impaired photoreceptor ribbon synapses to investigate the importance of intact ribbon synaptic active zones for signal transmission at Off cone bipolar cell contacts. Whole-cell patch-clamp recordings from Off cone bipolar cells in a horizontal slice preparation of wildtype (Bsnwt ) and mutant (BsnΔEx4/5 ) mouse retina were applied to investigate signal transmission between cone photoreceptors and Off cone bipolar cells. The distribution of postsynaptic glutamate receptors in Off cone bipolar cell dendrites was studied using multiplex immunocytochemistry. Tonic synaptic activity and evoked release were significantly reduced in mutant animals. Vesicle replenishment rates and the size of the readily releasable pool were likewise decreased. The precisely timed transient current response to light offset changed to a sustained response in the mutant, exemplified by random release events only loosely time-locked to the stimulus. The kainate receptor distribution in postsynaptic Off cone bipolar cell dendritic contacts in BsnΔEx4/5 mice was largely disturbed. Our results suggest a major role of functional ribbon synaptic active zones for signal transmission and postsynaptic glutamate receptor organization at flat Off cone bipolar cell contacts.


Immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine in 23-valent pneumococcal polysaccharide vaccine-naïve and previously immunized adult patients with severe chronic kidney disease.
Individuals with chronic kidney disease (CKD) are at high risk of pneumococcal infections and recommended to receive the 23-valent pneumococcal polysaccharide vaccine (PPV23). Although the 13-valent pneumococcal conjugate vaccine (PCV13) has been found to have higher immunogenicity compared to PPV23 in adults with some immunocompromising conditions, previous PPV23 immunization may decrease the immunogenicity of PCV13. We assessed immunogenicity and safety of PCV13 in 74 PPV23-naïve and 58 previously PPV23-immunized (>1 year ago) patients with severe (stage 4-5) CKD. Serum IgG, IgM, and IgA specific to seven serotypes, i.e. 3, 6B, 9V, 14, 19A, 19F, 23F were quantified pre- and 4 weeks and one year post-immunization. Baseline concentrations for most serotype-specific IgG and IgM, and serotype 3-specific IgA were higher in previously PPV23-immunized compared to PPV23-naïve patients. Immunization with PCV13 significantly increased almost all serotype-specific IgG, all IgA and some IgM; an increase in some serotype-specific IgG and IgM lasted for one year. Fold increases in antibody concentrations and the proportion of individuals with >2-fold increase post-immunization were generally larger in PPV23-naïve than previously immunized patients for most serotype-specific IgG and some IgA. The data show that in patients with CKD who received previous PPV23 immunization over one year ago, the antibody response to PCV13 was inferior compared to pneumococcal vaccine naïve study participants. In both groups, the lowest response to PCV13 was found for serotype 3. Patients of Indigenous ethnic background demonstrated a superior immune response to PCV13 compared to the non-Indigenous counterpart that could partially be related to Indigenous study participants' younger age. Although we found that previous PPV23 immunization could contribute to the more frequent occurrence of systemic adverse events post PCV13 immunization, those did not exceed the mild to moderate range.


Evaluation of post-radiofrequency myocardial injury by measuring cardiac troponin I levels.
The aim of this study was to investigate the extent of myocardial injury created by radiofrequency (RF) ablation. We assessed the changes in levels of cardiac biochemical markers in patients who underwent RF ablation and we sought to evaluate the utility of cardiac troponin I (cTnI) in detecting minor myocardial injury following RF ablation and determine its procedural correlates. We analyzed the data of 115 consecutive patients who underwent RF ablation. The target sites of RF ablation were slow pathway in 56, left atrioventricular (AV) annulus in 31, right AV annulus in 14, atrial wall in 3, ventricular wall in 6 and AV node in 3 patients. The levels of creatine kinase (CK), CK-MB, cTnI and myoglobin were compared with procedural data and targeted arrhythmia. Post-RF ablation the concentration of cTnI, CM-MB, CK and myoglobin were significantly different than those of the initial sample. The mean and peak cTnI levels were raised above normal in 63 patients (54.8%). Mean levels of cTnI correlated with the site of RF ablation, being significant for slow pathway ablation, ventricular tachycardia and left AV annulus. We also found a significant association of mean CK-MB, CK levels and left AV annulus. Our results indicate that radiofrequency ablation results in only minor injury. This marker is effective for detection of RF current induced myocardial injury. Lesions applied to the mitral annulus at the ventricular endocardium are associated with significantly greater myocardial damage.


[Value of the neuropsychological examinations in the diagnosis of supratentorial gliomas].
The authors report an analysis of the results of neuropsychological investigations of patients treated for supratentorial gliomas. A syndrome of the most frequently observed disturbances of higher nervous activity has been outlined. The diagnostic, localizatlry and differential diagnostic value of neuropsychological investigations has been assessed and found to a useful auxiliary clinical method.


Modeling hydraulic transport and anaerobic uptake by PAOs and GAOs during wastewater feeding in EBPR granular sludge reactors.
New-generation bioprocesses using granular sludge aim for a high-rate removal of nutrients from wastewater with low footprint. Achieving enhanced biological phosphorus removal (EBPR) relies on the design of sludge beds and wastewater feeding conditions to optimally load the biomass and to select for polyphosphate- (PAOs) over glycogen-accumulating organisms (GAOs) and over other heterotrophs. A hydraulic-metabolic mathematical model was developed to elucidate the impact of hydraulic transport patterns and environmental conditions on the PAO/GAO competition during up-flow feeding through an EBPR granular sludge bed. Tracer experiments highlighted plug-flow regimes with dispersion under both rapid (9 m h-1 , Rebed = 1.6, Pez = 7.2, Pet = 4.6) and slow (0.9 m h-1 , Rebed = 0.2, Pez = 21.3, Pet = 3.4) feeding. Non-turbulent regimes (Rebed << 103 ) promote a safe implementation of simultaneous fill/draw. Feeding time, pH, and temperature significantly impacted bacterial competition for carbon uptake under anaerobic slow feeding. Feeding duration should be designed to avoid full depletion of intracellular storage polymers within static granules. PAOs bear twice longer feeding than GAOs by using both polyphosphate and glycogen hydrolysis to sustain anaerobic C-uptake. Alkaline conditions (pH 7.25-8.0) by, e.g., dosing lime in the feed select for PAOs independently of temperature (10-30°C). A twice higher bed is required for full anaerobic conversions at 10 rather than 20°C. Biosystem responses for anaerobic C-uptake can be anticipated using the model toward designing robust anaerobic selectors to manage the microbial resource in EBPR granular sludge. Biotechnol. Bioeng. 2017;114: 1688-1702. © 2017 Wiley Periodicals, Inc.


The role of the psychologist in the treatment of spinal cord injury.
Advances in the treatment of spinal cord injury have shifted the emphasis from problems of survival to problems of psychological integration into the community. However, the patient's expectations for a fairly normal life are often not realised because of discrimination against disabled persons by able-bodied persons. Therefore, rehabilitation should include psychosocial skills training to teach spinal cord injury persons to cope with these issues in their own world. To accomplish this, the psychologist can contribute to the rehabilitation process as a consultant to the rehabilitation team, as a researcher of the rehabilitation process, as an evaluator of patient skills and strengths, and as a counselor. Each of these roles is discussed and a conceptualisation of the rehabilitation process is presented.


Intense parenting: a qualitative study detailing the experiences of parenting children with complex care needs.
Increased numbers of children with chronic illnesses and/or disabilities who have complex care needs are living at home. Along with the transfer of care to the home setting, parents assume the primary responsibility of their child's complex care needs. Accordingly, it becomes even more important to understand the evolving roles and challenges faced by parents of children with complex care needs in order to better support them. The aim of this paper is to present research findings that add to our understanding of the roles parents assume in parenting their children with complex care needs. To arrive at a detailed and accurate understanding of families' perspectives and experiences, the qualitative research design of ethnography was used. In total, 68 parents from 40 families were recruited. Data collection strategies included ethnographic methods of interviewing and photovoice. Several levels of analysis generated a sociocultural theme with subthemes representing how parents experienced raising children with complex care needs within the context of their life situations. Intense parenting as the overarching theme refers to the extra efforts parents had to commit to in raising their children with complex care needs. Parenting was described as labour-intensive, requiring a readiness to provide care at any time. This left parents with minimal time for addressing any needs and tasks not associated with caring for their child. The main theme is supported by four sub-themes: 1) the good parent; 2) more than a nurse; 3) there's just not enough; 4) it takes a toll on the health of parents. Overall, parents of children with complex care needs take on more roles as well as work more intensely at these roles than parents of healthy children. This, in turn, has led to the need for additional supports and resources for parents. However, to date, parents of children with complex care needs are still lacking adequate services and supports necessary to help them in their role of intense parenting. The findings sensitize professionals to the issues confronted by parents caring for children with complex care needs. Implications for further research and clinical practice are discussed.


Efficiency of Hypertonic Saline in the Management of Decompensated Heart Failure: A Systematic Review and Meta-Analysis of Clinical Studies.
Acute decompensated heart failure (ADHF), with an incidence of 1-2%, is a clinical syndrome with significant morbidity and mortality despite therapeutic advancements and ongoing clinical trials. A recent therapeutic approach to patients with ADHF includes combination therapy with hypertonic saline solution (HSS) and furosemide, based on the hypothesis that resistance to loop diuretics occurs because of achievement of plateau in water and sodium excretion in patients receiving long-term loop diuretic therapy. Our aim was to conduct a meta-analysis to evaluate the efficiency of combination HSS plus furosemide therapy in patients with ADHF in terms of mortality, readmissions, length of hospital stay, kidney function, urine output, body weight, and B-type natriuretic peptide (BNP). A total of 14 studies-four observational and ten randomized studies (total 3398 patients)-were included in the meta-analysis. Our results demonstrate the superiority of combination HSS plus furosemide therapy over furosemide alone in terms of kidney function preservation (mean creatinine difference - 0.33 mg/dL; P < 0.00001), improved diuresis (mean difference [MD] 581.94 mL/24 h; P < 0.00001) and natriuresis (MD 57.19; P < 0.00001), weight loss (MD 0.99 kg; P < 0.00001), duration of hospital stay (MD - 2.72 days; P < 0.00001), readmissions (relative risk 0.63; P = 0.01), and mortality (relative risk 0.55; P < 0.00001). However, no difference in BNP levels was detected (MD 19.88 pg/mL; P = 0.50). Despite the heterogeneity and possible risk of bias among the studies, results appear promising on multiple aspects. A clear need exists for future randomized controlled trials investigating the role of combination HSS plus furosemide therapy to clarify these effects and their possible mechanisms.


Role of family in supporting children with mental disorders in Qatar.
Mental disorders can significantly impact children's lives and affect their emotional, cognitive, and behavioral development. Family support and care is critical to the well-being of children, particularly children with mental disorders. However, given the "gap" between research and practice"," there have been very few studies in the Arab region that focus on the role of the family in supporting children with mental disorders. The study also examines how families cope with caring for a person with mental disorders and what behaviors may influence the patient's distress. In addition, the study will examine the importance of family rehabilitation and integration of people with mental disorders into society. The study adopts the descriptive-analytical method and uses a questionnaire to gather data from the participants. The 350-parents sample (with 113 boys, 237 girls) was selected from the Shafallah Center for Integrating People with Disability. Morgan's law is used to determine the sample size. The results show that there are statistically significant differences in the role of family members in supporting people with mental disorders due to two variables: Gender and Work. Age has no statistically significant effect on the role of family members in supporting people with mental disorders. This study is the first study conducted to investigate the role of family in supporting children with mental disorders in the Gulf Cooperation Council (GCC) in general and Qatar in particular. The results show that families should cope with the needs of a person with a mental disorder. Family rehabilitation is important in the care of people with mental disorders. There are certain behaviors of family members that can increase or decrease stress for the person. The results suggest that the family plays an essential role in supporting and promoting the lives of people with mental disorders and recommending effective ways to cope with them.


Protective effect of amifostine on high-dose methotrexate-induced small intestinal mucositis in mice.
Amifostine has been shown to be capable of minimizing radiotherapy-induced oral mucositis, but whether it protects small intestinal mucosae from high-dose methotrexate-induced damage is presently unknown. We aimed to evaluate the protective effect of amifostine against high-dose methotrexate-induced small intestinal mucositis and its mechanism. Ninety Kunming mice were randomly divided into five experimental groups: saline control; high-dose methotrexate (HDMTX) group: treated with a single high dose of methotrexate; calcium folinate (CF) group: treated with high-dose methotrexate followed with CF; Amifostine group: treated with amifostine, followed with high-dose methotrexate; and amifostine-CF group: treated with amifostine pre-high-dose methotrexate and followed by CF post-high-dose methotrexate. Mouse weight, villus height and crypt depth, stool consistency, white blood cell count, death and survival were recorded. Bax and Bcl-2 mRNA expression were quantified by semi-quantitative PCR. Compared to the mice treated with HDMTX, CF, and amifostine, mice treated with Amifostine-CF group were heavier and had greater villus height, crypt depth, and normal white blood cell count and lower diarrhea rate and mortality than the HDMTX, CF and amifostine groups. There was a significant decrease in enterocyte apoptosis in amifostine-CF mice compared with the HDMTX and CF groups. The effect of amifostine plus CF was greater than amifostine or CF alone in preventing high-dose methotrexate-induced intestinal mucositis and improving intestinal recovery in mice.


Multiple variations of the coeliac axis, hepatic and renal vasculature as incidental findings illustrated by MDCTA.
Vascular anatomical variations are not uncommon and may affect any organ's arterial or venous vasculature. The coexistence of variations in different organic systems is less commonly found, but of great clinical significance in a series of clinical conditions like organ transplantation and surgical preoperative planning. Multidetector computed tomography angiography (MDCTA) has emerged as a valuable alternative to the conventional angiography for accurate evaluation of vascular anatomy and pathology. Radiologists should be familiar with each organ's vascular variations and always report them to the clinician, even if they represent an incidental finding. This case report presents a 52-year-old female patient undergoing abdominal MDCTA for characterization of a renal lesion. This examination revealed the presence of three hilar arteries on the left kidney, a main renal vein in combination with an additional renal vein in both sides along with a replaced right hepatic artery originating from the superior mesenteric artery. Moreover, both inferior phrenic arteries were found originating from the coeliac axis. 3D volume rendering technique images were used in the evaluation of vascular anatomy as illustrated in this case report.


A patient came back with retrograde coronary flow in the distal right coronary artery 2 years after coronary intervention: clinical significance of retrograde coronary flow to detect coronary artery occlusion.
A 69-year-old male patient, who had a history of coronary stent implantation to the proximal right coronary artery (RCA), presented with exertional chest pain. Transthoracic Doppler echocardiography revealed retrograde coronary flow in the distal RCA, and treadmill stress echocardiography revealed inducible myocardial ischemia in the inferior and posterior segments. Coronary angiography demonstrated a severe stenotic lesion with flow delay in the mid RCA and collateral circulation to the distal RCA from the left coronary artery. Detection of retrograde coronary flow in the distal RCA using transthoracic Doppler echocardiography is a useful method to diagnose subtotal occlusion of the RCA.


Gene frequencies of human platelet antigens on glycoprotein IIIa in Japanese.
Polymorphism of glycoprotein IIIa on human platelets is one of the factors in alloimmunization that causes neonatal alloimmune thrombocytopenia and refractoriness to platelet transfusion. DNA typing methods were originally developed to determine the genotypes of five human platelet antigen (HPA) systems located on glycoprotein IIIa: HPA-1, HPA-4, HPA-6W, HPA-7W and HPA-8W. The gene frequencies of these platelet antigens were determined by DNA typing of 331 unrelated Japanese donors. The gene frequencies of the low-frequency antigens were 0.002, 0.011, and 0.027 for HPA-1b, HPA-4b, and HPA-6W(b), respectively. All 331 Japanese donors tested were HPA-7W(a/a) and HPA-8W(a/a). Moreover, in the present study, none of the donors tested had two or more of these low-frequency antigens. The risk of neonatal alloimmune thrombocytopenia and refractoriness to platelet transfusion induced by the antigens of the HPA-1, HPA-7W, and HPA-8W systems was extremely rare in Japanese. However, attention must be paid to the involvement of the HPA-4 and HPA-6W systems in these clinical disorders.


Chronic paroxysmal hemicrania and hemicrania continua: orbital phlebography and MRI studies.
Six patients with chronic paroxysmal hemicrania (CPH) and 10 patients with hemicrania continua (HC), two indomethacin-responsive, unilateral, headache syndromes, were investigated with orbital phlebography and magnetic resonance imaging of the brain. Orbital phlebography apparently showed pathological findings more frequently in CPH than in HC. Such abnormalities did not always show preference for the side of headache. MR scans were grossly normal in these headaches.


ROS antagonizes the protection of Parkin-mediated mitophagy against aluminum-induced liver inflammatory injury in mice.
Aluminum (Al) is a food pollutant that has extensive deleterious effects on the liver. Our previous research proposed that E3 ubiquitin ligase PARK2 knockout (Parkin-/-) could aggravate Al-induced liver damage by inhibiting mitophagy, during which the reactive oxygen species (ROS) content increases. Inhibition of mitophagy can activate inflammasome. But the link between Parkin-mediated mitophagy and liver inflammatory injury caused by Al, and the role of ROS in it remain unclear. In this study, we applied Al, Parkin-/- and N-acetyl-L-cysteine (NAC) to act on C57BL/6N mice to investigate them. We found that Al could induce liver inflammatory injury and Parkin-/- could aggravate it. Meanwhile, inhibition of ROS alleviated oxidative stress, mitochondrial damage, mitophagy and inflammatory injury caused by Al in Parkin-/- mice liver. These results indicated that ROS antagonized the protection of Parkin-mediated mitophagy against Al-induced liver inflammatory damage in mice.


Genetic Control of Alternative Splicing and its Distinct Role in Colorectal Cancer Mechanisms.
Dysregulation of alternative splicing is implicated in many human diseases, and understanding the genetic variation underlying transcript splicing is essential to dissect the molecular mechanisms of cancers. We aimed to provide a comprehensive functional dissection of splicing quantitative trait loci (sQTLs) in cancer and focus on elucidating its distinct role in colorectal cancer (CRC) mechanisms. We performed a comprehensive sQTL analysis to identify genetic variants that control messenger RNA splicing across 33 cancer types from The Cancer Genome Atlas and independently validated in our 154 CRC tissues. Then, large-scale, multicenter, multi-ethnic case-control studies (34,585 cases and 76,023 controls) were conducted to examine the association of these sQTLs with CRC risk. A series of biological experiments in vitro and in vivo were performed to investigate the potential mechanisms of the candidate sQTLs and target genes. The molecular characterization of sQTL revealed its distinct role in cancer susceptibility. Tumor-specific sQTL further showed better response to cancer development. In addition, functionally informed polygenic risk score highlighted the potentiality of sQTLs in the CRC prediction. Complemented by large-scale population studies, we identified that the risk allele (T) of a multi-ancestry-associated sQTL rs61746794 significantly increased the risk of CRC in Chinese (odds ratio, 1.20; 95% CI, 1.12-1.29; P = 8.82 × 10-7) and European (odds ratio, 1.11; 95% CI, 1.07-1.16; P = 1.13 × 10-7) populations. rs61746794-T facilitated PRMT7 exon 16 splicing mediated by the RNA-binding protein PRPF8, thus increasing the level of canonical PRMT7 isoform (PRMT7-V2). Overexpression of PRMT7-V2 significantly enhanced the growth of CRC cells and xenograft tumors compared with PRMT7-V1. Mechanistically, PRMT7-V2 functions as an epigenetic writer that catalyzes the arginine methylation of H4R3 and H3R2, subsequently regulating diverse biological processes, including YAP, AKT, and KRAS pathway. A selective PRMT7 inhibitor, SGC3027, exhibited antitumor effects on human CRC cells. Our study provides an informative sQTLs resource and insights into the regulatory mechanisms linking splicing variants to cancer risk and serving as biomarkers and therapeutic targets.


High-resolution bioenergetics correlates the length of continuous protonatable diaminoethane motif of four-armed oligo(ethanamino)amide transfectants to cytotoxicity.
Recent clinical success with Onpattro and cationic ionizable lipid nanoparticle-based mRNA vaccines has rejuvenated research in the design and engineering of broader synthetic cationic vectors for nucleic acid compaction and transfection. However, perturbation of metabolic processes and cytotoxicity are still of concern with synthetic cationic vectors. Here, through an integrated bioenergetic and biomembrane integrity probing in three different human cell lines we reveal the dynamic effect of a library of sequence-defined four-arm oligo(ethanamino)amide transfectant on cell homeostasis, and identify metabolically safe building units over wide concentration ranges. The results show differential effects of the oligo(ethanamino)amide structure of comparable molecular weight on cell energetics. The severity of polycation effect on bioenergetic crisis follows with the length of continuous protonatable diaminoethane motif in the ascending order of glutaryl-triethylene tetramine, succinyl-tetraethylene pentamine and succinyl-pentaethylene hexamine. We further identify oligomeric structures that do not induce bioenergetic crisis even at high concentrations. Finally, transfection studies with a library of polyplexes carrying a reporter gene show no correlation between transfection efficiency and cytotoxicity. These observations demonstrate the usefulness of integrated high-resolution respirometry and plasma membrane integrity probing as a highly sensitive medium-throughput screening strategy for identification and selection of safe building units for transfectant engineering.


Hormone-induced and maturational changes in electric organ discharges and electroreceptor tuning in the weakly electric fish Apteronotus.
Plasticity in the frequency of the electric organ discharge (EOD) and electroreceptor tuning of weakly electric fish was studied in the genus Apteronotus. Both hormone-induced and maturational changes in EOD frequency and electroreceptor tuning were examined. Apteronotus is different from all other steroid-responsive weakly electric fish in that estradiol-17 beta, rather than androgens, induces discharge frequency decreases. This result can account for the 'reversed' discharge frequency dimorphism found in Apteronotus in which, counter to all other known sexually dimorphic electric fish, females have lower discharge frequencies than males. Studies of electroreceptor tuning in Apteronotus indicate that electroreceptors are closely tuned to the frequency of the EOD. This finding was noted not only in adult animals, but also in juvenile animals shortly after the onset of their EODs. Tuning plasticity in Apteronotus, as in other species studied, is associated with altered EOD frequencies and was noted in both maturational EOD changes and in estrogen-induced changes. Thus, tuning plasticity appears to be a general phenomenon which occurs concurrent with a variety of EOD changes.


Determination of optimal time window for liver scanning with CT during arterial portography.
To determine the optimal time window for scanning the liver with computed tomography (CT) during arterial portography (CTAP). After vasodilation and contrast medium injection into the superior mesenteric artery (80 mL at 5 mL/sec), 25 repeated scans were obtained at a single level within 83 seconds in 13 patients. Attenuation was measured on every scan, and time-attenuation curves were created. Enhancement characteristics of the portal vein, liver parenchyma, aorta, and tumors were evaluated. Parenchymal enhancement of more than 60 HU was achieved between 18 seconds +/- 4 (standard deviation) and 67 seconds +/- 15, and high parenchyma-to-tumor contrast of more than 50 HU occurred between 18 seconds +/- 3 and 62 seconds +/- 14. To scan the liver within such a narrow time window, a spiral CT technique is necessary. When the above injection parameters are used in CTAP, the spiral CT sequence should be started 20 seconds after the beginning of the injection.


Murine hemopoietic colonies in culture containing normoblasts, macrophages, and megakaryocytes.
Murine marrow cells, when incubated in methylcellulose culture in the presence of erythropoietin and conditioned medium for two weeks, produced large macroscopic bursts containing normoblasts, macrophages, and often megakaryocytes. The clonal nature of these mixed colonies was supported by linearity studies and analysis of the percentages of constituent cells in different plating conditions. Time course observations and studies of the effects of L-cell-conditioned medium revealed that colony-forming cells for the mixed colonies (CFU-mix) are at earlier stages of hemopoietic development than burst-forming units (BFU-E). The mean of the modal sedimentation velocities of CFU-mix was 3.4 mm/hr and was in close agreement with that reported for the spleen colony-forming units. Almost none of the CFU-mix was in a DNA synthetic phase as measured by short-term exposure to tritiated thymidine. These results strongly indicate that CFU-mix represent a population of pluripotent hemopoietic stem cells in murine marrow.


Evaluating connectivity risk of farm roadway runoff with waters - Development and sensitivity analysis of a semi quantitative risk model.
Farm roadways are an important sub-component of the nutrient transfer continuum (NTC) and roadway runoff (RR), leading to nutrient pressures in receiving waters at different times of the year at catchment scale. This study developed a semi-quantitative risk assessment model for dairy farms that once populated with data identifies roadway sections where RR enters waters. The model contains parameters that represent source, mobilisation and transport-connectivity stages of the NTC defined as continuous or categorical variables. Each parameter has a corresponding scoring system in terms of connectivity likelihood to waters (L) and the associated impact on water quality (I) from which field data can be converted to a risk score (RS). The connectivity or impact risk of any roadway section is a sum of all parameter scores, i.e. 'Total Risk Score' (TRS). The risk scores were classified into 5 categories (very low, low, moderate, high and very high). Field data from seven farms enabled five equal interval risk score classifications to be developed (very low (110-134), low (135-158), moderate (159-182), high (183-206), very high (207-230)). Fieldwork data showed differences between the number of mapped roadway sections ranging from 35 to 76, with the lowest and highest risk scores being 110 and 230, respectively. Out of all sections scored 25.9 %, 45.6 %, 20.4 %, 6.4 %, and 2 % were in very low, low, moderate, high and very high categories, respectively. In terms of management, only 8.4 % (i.e. high or very high scores) had all components of the NTC and required RR mitigation. An examination of the mobilisation parameter showed that the % of roadway sections needing mitigation is likely to increase if rainfall increases on these farms. An uncertainty assessment limiting the model to different levels of connectivity confirmed that all components of the NTC and those with greater than moderate risk should only be considered in future mitigation plans. Future work should concentrate on adapting this methodology to a wide range of farm enterprises.


Tricuspid Annular Plane Systolic Excursion (TAPSE) for Risk Stratification and Prognostication of Patients with Pulmonary Embolism.
The categorization of pulmonary embolism (PE) as non-massive, sub-massive, and massive helps guide acute management. The presence of right ventricular (RV) strain differentiates sub-massive from non-massive PEs. Unlike laboratory markers and electrocardiogram changes, the classic parameters used in the echocardiographic diagnosis of RV strain have a technical component that is operator-dependent. This narrative review will describe the physiologic effects of a PE on the RV and how this affects prognosis. It will summarize the literature evaluating the accuracy and prognostic ability of tricuspid annular plane systolic excursion (TAPSE) in the echocardiographic assessment of RVfunction. The review will describe the appeal of TAPSE for this purpose, provide cutoff measurements, and then illustrate how to perform the technique itself, while offering associated pearls and pitfalls in this bedside evaluation. RV function and dynamics undergo acute changes in the setting of a PE. RV dysfunction predicts poor outcomes in both the short and long term. However, RV strain is difficult to capture on echocardiography due to the chamber's complex geometric shape and contraction. From the apical four-chamber window, TAPSE offers a quantitative measure that is more easily performed with high interobserver reliability for evaluating systolic RV contraction. This measurement carries prognostic value in patients diagnosed with PE. Along with other more qualitative echocardiographic parameters, TAPSE can be used as a simple quantitative measure of RV dysfunction for differentiating sub-massive from non-massive PEs. This categorization helps guide acute management and disposition.


Attitudes among junior doctors towards improving the transurethral catheterisation process.
To evaluate the subjective opinions of junior doctors on their adequacy of training and confidence levels for performing transurethral catheterisation (TUC) and to investigate their subjective interest in a 'safety mechanism' that would eliminate the potential for urethral trauma during TUC. An anonymous online survey was emailed to all interns that had a documented email address on the Royal College of Surgeons Ireland registry (2012-2013). The survey consisted of eight questions pertaining to TUC of male patients. The survey was delivered to 252 email addresses and the response rate was 52% (130/252). The vast majority (99%; n = 128) of interns felt confident inserting a transurethral catheter independently and 73% (n = 95) subjectively received appropriate training for catheterising male patients. The incidence of trauma after mistakenly inflating the catheter's anchoring balloon in the urethra was 3% (n = 4). The majority (90%; n = 116) of respondents were interested in a safety mechanism for preventing urethral trauma and 71% (n = 92) felt that a safety mechanism for urethral trauma prevention should be compulsory for all transurethral catheterisation among male patients. Despite pre-emptive training programmes, it appears that iatrogenic urethral trauma secondary to TUC remains a persistent morbidity in healthcare settings. Designing a safer transurethral catheter may be necessary to eliminate the risk of unnecessary urethral trauma in patients.


Palladium catalyzed alkenyl amination: from enamines to heterocyclic synthesis.
The most recent advances in the Pd catalyzed amination of alkenyl halides directed towards the synthesis of imines and enamines are reviewed. The application of this cross-coupling reaction in the synthesis of heterocycles appears to be a potentially powerful methodology. The few examples already available are also discussed.


Biomarkers of exposure to vitamins A, C, and E and their relation to lipid and protein oxidation markers.
Since antioxidant vitamins may affect an organism's capacity for defence against reactive oxygen species, biological markers of the dietary exposure to these vitamins is of importance. There is also a need of effect biomarkers for determining the ability of these and other antioxidants to increase the overall antioxidant capacity and decrease the oxidative damage occurring in biological samples. This review is concerned with exposure markers and markers of lipid- or protein damage following intervention with vitamins A, C and E. While there are several high quality exposure markers available it is not possible to identify functional markers of lipid or protein oxidation, which respond reliably to human dietary intervention with vitamins A, C or E.


Systemic acyl-ghrelin increases tail skin temperature in rats without affecting their thermoregulatory behavior in a cold environment.
Fasting increases ghrelin that is a peptide hormone with two circulating isoforms, acyl and des-acyl ghrelin. We reported that fasting or des-acyl ghrelin facilitates behavioral thermoregulation in the cold in rats assessed by tail-hiding behavior that was the indicator of rats' thermoregulatory behavior in the cold; however, the effect of acyl-ghrelin on the same process remains to be elucidated. We investigated the effect of acyl-ghrelin on thermoregulatory behavior in the cold in rats. The animals received an intraperitoneal saline or 24 μg acyl-ghrelin injection and were exposed to 27 °C or 15 °C for 2 h, while their body temperature, tail skin temperature, and tail-hiding behavior were constantly monitored. cFos immunoreactive (cFos-IR) cells in the median preoptic area, medial preoptic area, paraventricular nucleus (PVN), and arcuate nucleus were counted. Body temperature and the duration of thermoregulatory behavior did not show a significant difference between the acyl-ghrelin-treated and control groups at 15 °C; however, tail skin temperature in the acyl-ghrelin-treated group was higher than that in the control group. The number of cFos-IR cells in the PVN was greater in the control group than that in the acyl-ghrelin-treated group at 27 °C. These results indicate that acyl-ghrelin did not affect behavioral thermoregulation but might affect tail skin temperature in rats in the cold.


[5 years ofFusaria and mycotoxin monitoring - any use for practice?].
Since 1999 the harvest of grain in Mecklenburg-Vorpommern has been investigated yearly as to its Fusaria infection rate and contamination with mycotoxins. 376 samples, most of them winter wheat, were tested for the mycotoxins zearalenone and deoxynivalenol in 1999-2003. The investigations were carried out with an ELISA; some results were confirmed by a chromatographic method (HPLC). In 2002 the Fusaria infection rate was graded as moderate (17,4%), in the other years as low (max. 9%). Zearalenone was detected only in 2,7% of the samples (max.236 μg/kg). 9,6% of samples contained deoxynivalenol (max. 1,2 mg/kg). Therefore the mycotoxin contamination in grain, harvested in Mecklenburg-Vorpommern 1999-2003 and the risk for consumers and animals as well is thought to be low. These results should help the farmers to understand that mycotoxins are not necessarily the sole cause of depressions in yield and loss of animals. It should be possible to avoid a false interpretation of mycotoxin findings.


Development of a passive device for freezing large amounts of transplantable skin at one time in a -70 degrees C mechanical refrigerator.
A simple device has been developed for the simultaneous cooling of up to 9120 cm2 of allograft skin in a flat package format. The device, named an insulated alternating-offset heat sink device, is composed of a stack of interleaved layers of 2.0-mm-thick packets of skin and 3.18-mm-thick aluminum heat sinks (each 33.0 cm long by 22.9 cm wide). Four skin packets are placed in a single layer on each heat sink plate, and the number of plates can be varied to accommodate different numbers of skin packets. Every heat sink protrudes 6.3 cm of its 33.0-cm length beyond the skin packets to make a fin for heat convection, but adjacent plates alternate the direction of their fin protrusion so that the layers of plates alternate in their 6.3-cm offset. Insulation layers of 2.54-cm-thick expanded polystyrene are placed on the exposed surfaces of the top and bottom heat sinks in the stack, and the stack is held together by rubber bands. The device is cooled in a -70 degrees C mechanical refrigerator. Maximal cooling rates of -1.8 degrees C min-1 are obtained for both 6- and 11-plate devices, and -3.0 degrees C min-1 for a 2-plate device. The exothermic temperature plateaus associated with skin cooled in these devices are 1.5-1.8 min in duration. Skin cooled by this technique maintains levels of glucose oxidation similar to those associated with skin cooled by liquid nitrogen vapor at a controlled rate of -1 degree C min-1, provided rapid warming is employed after -70 degrees C storage. The development of this device provides a method for the simple, low-cost cryopreservation of the large amounts of allograft skin obtained from a cadaveric donor.


Transfusion medicine problems and solutions for the pediatric hematologist/oncologist.
Blood component transfusion is an integral part of the care of children with oncologic and hematologic conditions. The complexity of transfusion medicine may however lead to challenges for pediatric hematologists/oncologists. In this review, three commonly encountered areas of transfusion medicine are explored. The approach to the investigation and management of suspected platelet refractoriness is reviewed. The unique transfusion related challenges encountered by children undergoing stem cell transplantation are also discussed. Finally, issues arising out of the care of children with hemoglobinopathies are explored, with an emphasis on the incidence of allo- and autoimmunization.


Localised apparent masses over the interface between a seated human body and a soft seat during vertical whole-body vibration.
Vibration transmission through vehicle seats is usually predicted using the biodynamics of the seated human body measured with a rigid seat, however how coupling between the body and the seat would affect the biodynamics of the body is not considered. This study investigated how dynamic forces distributed over a soft seat compared to that over a rigid seat wtih vertical vibration excitation. Fourteen male subjects sitting on a rigid seat and on foam cushions of two different thickness with four different heights of footrest were exposed to vertical whole-body vibration between 0.5 and 20 Hz at 0.5 ms-2 r.m.s. Dynamic forces were measured beneath the ischial tuberosities, the middle thighs, and the front thighs and the transmissibility of the cushion was measured to the three locations. The resonance in the transmissibility of the cushion was found around 4 Hz to the ischial tuberosities but around 6-8 Hz to the front thighs. Differences between the apparent mass measured with the cushioned seat and the rigid seat decreased with increasing height of footrest. A multi-body dynamic model that can predict the dynamic forces beneath the ischial tuberosities and thighs was applied to identify the cause for the differences. It was suggested the differences can be caused by the variations in vibration over the surface of soft seats, especially when the contact area beneath the thighs was large, and by changes in the effective stiffness and damping of the human body when the contact area beneath the thighs was reduced.


Urinary androgens and tumor estrogen receptor as predictors of ovariectomy response and of survival in advanced breast cancer.
Estrogen receptor (ER) status and urinary androgen (A) concentration were simultaneously determined in 50 premenopausal patients submitted to bilateral ovariectomy for advanced carcinoma of the breast. When both the hormonal parameters were positive (ER+ A+), the response to castration was favorable in 87.5% of the cases, with a survival rate of 39% at 5 years. No patient responded to the therapy when both the parameters were negative (ER- A-); none of them was alive at 5 years. An intermediate response (more than 50%) and survival rate at 5 years (more than 20%) was obtained in the group of patients with at least one of the two parameters positive (ER+ A-, or ER- A+). These responses were independent of the topography of neoplastic localizations and the length of the disease-free interval.


Serotonin metabolism in the placenta in exacerbation of herpesvirus infection during pregnancy.
Serotonin metabolism in the blood and placental homogenate was studied in pregnancy aggravated by exacerbation of herpesvirus infection. Blood serotonin content in pregnant patients increased with increasing herpesvirus antibody titers and reduction of monoamine oxidase activity. Urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) decreased. The decrease of monoamine oxidase activity in placental homogenate led to an increase of serotonin level, which was paralleled by destruction of mitochondria in the syncytiotrophoblast, suppression of BCL-2 protein activity, and increase of caspase-3 level.


Novel dimensions of piRNAs in cancer.
Piwi-interacting RNAs (piRNAs), a newly identified class of small non-coding RNAs, direct the Piwi-dependent transposon silencing, heterochromatin modification and germ cell maintenance. Owing to our limited knowledge regarding their biogenesis, piRNAs are considered as the most mysterious class of small regulatory RNAs, particularly in pathogenesis such as tumorigenesis. Recently, several lines of evidence have emerged to suggest that piRNAs may be dis-regulated and play crucial roles in tumorigenesis in previously unsuspected ways. In this prospective piece, we will discuss the emerging insights into the potential novel roles of piRNAs in carcinogenesis and highlight their potential implications in cancer detection, classification and therapy.


Enhancing the magnetic anisotropy of maghemite nanoparticles via the surface coordination of molecular complexes.
Superparamagnetic nanoparticles are promising objects for data storage or medical applications. In the smallest--and more attractive--systems, the properties are governed by the magnetic anisotropy. Here we report a molecule-based synthetic strategy to enhance this anisotropy in sub-10-nm nanoparticles. It consists of the fabrication of composite materials where anisotropic molecular complexes are coordinated to the surface of the nanoparticles. Reacting 5 nm γ-Fe2O3 nanoparticles with the [Co(II)(TPMA)Cl2] complex (TPMA: tris(2-pyridylmethyl)amine) leads to the desired composite materials and the characterization of the functionalized nanoparticles evidences the successful coordination--without nanoparticle aggregation and without complex dissociation--of the molecular complexes to the nanoparticles surface. Magnetic measurements indicate the significant enhancement of the anisotropy in the final objects. Indeed, the functionalized nanoparticles show a threefold increase of the blocking temperature and a coercive field increased by one order of magnitude.


Intrapartum PCR-assay for detection of Group B Streptococci (GBS).
We have recently introduced intrapartum PCR-testing for group B streptococcus (GBS) in women in labor with prolonged rupture of membranes or preterm delivery to offer intrapartum antibiotic prophylaxis only for GBS positive women.The goal of the present study is to report our experience and results from the first half year of GBS testing. This is a retrospective study. Rectovaginal swabs from 321 women presenting in the labor ward with pre-labor rupture of membranes for >14 h/rupture of membranes during delivery for >14 h, or labor between gestational weeks 35 0/7 and 36 6/7 from February 7, 2017 to August 6, 2017, were tested.We performed a molecular GBS test (Xpert GBS®, Cepheid Ltd., Sunnyvale, USA).Data from patient files including mode of delivery, use of antibiotics, infection of mother and child are presented in more detail.Data on the PCR results from the first year of testing were also collected. In the first half-year of testing a positive GBS test result was found in 58 (18.1%) and a negative test result in 263 women (81.9%). No invalid test result was achieved.The indication for performing PCR testing was PROM > 14 h or rupture of membranes during labor for >14 h in 266 women (82.9%) and labor in gestational weeks 35 0/7-36 6/7 in 44 women (13.7%). In the remaining 11 women, the PCR test was performed for other reasons.Of the 321 women tested 126 (39%) received antibiotics during labor.Ten women (3.4%) were treated after delivery on suspicion of infection. 25 newborns (7.8%) were treated with antibiotics. In 11 cases, the treatment was stopped after 2-4 days as there were no signs of infection. The introduction of the intrapartum GBS test in selected groups of women who gave birth in our department has been well accepted by the women, the midwifes and doctors. The result of the test is available within two hours, and as we only offer intrapartum antibiotic prophylaxis to GBS-positive women, we have reduced the use of antibiotics to approximately 40% in the groups tested, without an increase of infection in mother or child.


Placenta previa percreta with fetal survival.
A case of placenta previa percreta accompanied by massive hemorrhage is described. Both the mother and fetus survived. Anticipation of this rare obstetric condition is both possible and essential for optimum management.


New triterpenic acids from Uncaria rhynchophylla: chemistry, NO-inhibitory activity, and tandem mass spectrometric analysis.
Five new oleanane and ursane type triterpenes, namely uncarinic acids F-J (1-5), together with six known triterpenic acids (6-11) were isolated from the stems and hooks of Uncaria rhynchophylla. Structure elucidation of 1-5 was based on the integrated analyses of high-resolution MS data, 1D ((1)H NMR, (13)C NMR, DEPT) and 2D (HSQC, HMBC, ROESY) NMR spectra. Compounds 4, 10, and 11 exhibited weak inhibitory effects on LPS-induced NO production in RAW264.7 cells (with IC50 1.48, 7.01, and 1.89 μM, respectively) with dexamethasone (IC50 0.04 μM) and quercetin (IC50 0.86 μM) as the positive controls. 19-OH substituted oleanane triterpenic acids (1, 2, 5, 8) were prone to eliminate CH2O3, whereas those ursane-type encompassing 19-OH (3, 6, 7, 9, 4) were featured by preferred cleavage of H2O while performing the negative collision-induced MS/MS fragmentation on an LTQ/Orbitrap mass spectrometer.


Improvement of a cytokine (TNF-α) bioassay by serum-free target cell (WEHI 164) cultivation.
The elaboration of a sensitive bioassay for assessment of tumour necrosis factor alpha (TNF-α) in a defined medium is described. The assay is based on the cytotoxic effect of TNF-α on a target cell line, the murine fibrosarcoma WEHI 164 clone 13. Cytotoxicity was assessed by detecting the rate of tetrazolium salt reduction employing a spectrophotometer (ELISA-reader). A similar bioassay was used previously to assess TNF-α, though this was dependent on cell growth in a medium containing serum. By employing a synthetic serum replacement, the WEHI cells were adapted to growth in a defined medium which allowed both the propagation of the cell line and the assay to be performed under completely defined conditions. Thus, factors in serum that may influence the TNF-α assessment, such as growth factors, cytokines, soluble cytokine-receptors and macroglobulin, were avoided. The only protein required in this bioassay was insulin, while albumin was added as a carrier protein and to protect the cytokine against loss of biological activity during multiple freeze and thaw cycles. The present assay was optimised to achieve a high sensitivity and, by testing endogenous TNF-α originating from the macrophage-like cell line RAW in both the serum-free and serum-based assay, we found the highest sensitivity in the assay based on defined medium. The LC50 of recombinant mouse and human TNF-α were in the serum-free and serum-based assays considered to be 25 and 50 pg mL-1, respectively. The demonstration of a culture condition that enables long-term cultivation of target cells and a bioassay in a completely defined medium is in our opinion a substantial contribution to more reliable cytokine assessment.


Effects of upper dorsal sympathectomy on esophageal motility in humans.
To evaluate the role of the sympathetic nervous system in modulating esophageal motility, esophageal manometry was performed on two groups of patients who underwent upper dorsal sympathectomy for relief of palmar hyperhydrosis. In six patients sympathectomy was done by the supraclavicular approach, with removal of T2 and T3 ganglia. Manometry was performed before the operation and three weeks after it. In seven other patients sympathectomy was done by the axillary approach, with removal of T2-T4 ganglia. Manometry in this group was performed 28.4 +/- 22.4 months after the operation. Fifteen individuals with an intact sympathetic system served as controls. Manometric parameters evaluated were esophageal contraction amplitude and duration and lower esophageal sphincter pressure. The difference between the results obtained in the pre- and postoperative periods in the first group was not statistically significant. The differences between the two patient groups and between the patient groups and the control group were not statistically significant either. We conclude that upper dorsal sympathectomy does not affect esophageal motility in man.


Herbal supplements.
Herbal dietary supplements are taken by many individuals, often without the knowledge of their clinicians. Herbals have many pharmacologic and medicinal properties but are unregulated with respect to manufacturing purity, safety, and efficacy. Although clinicians often dismiss the utility of herbal therapy, many randomized controlled trials of herbal use in gastrointestinal and liver diseases have been conducted. There is no evidence for benefit from herbal supplements in the treatment of liver disease, but sufficient evidence exists for their use in functional gastrointestinal symptoms to warrant further investigation.


Corrigendum: IL-3 produced by T cells is crucial for basophil extravasation in hapten- induced allergic contact dermatitis.
[This corrects the article DOI: 10.3389/fimmu.2023.1151468.].


[Use of silicon-impregnated compresses for echographic detection of section planes during hepatectomies].
It is essential to detect section planes during hepatectomy, notably for limited resections in cirrhotic patients. The authors describe a technical artifice, the use silicon-impregnated compresses, to help in the peroperative ultrasonographic detection of these section planes.


Weight gain promotes the progression of IgA nephropathy in Asians: A protocol for systematic review and meta-analysis.
The relationship between weight gain and progression of IgA nephropathy (IgAN) has been investigated by many researchers but remains controversial. The incidence of IgAN is significantly higher in Asia than in other regions. Therefore, we investigated the relationship between weight gain and primary IgAN in the Asian population. Seven databases were retrieved up to now. We stratified the included population by body mass index (BMI) and performed a meta-analysis of associated risk factors. In this study, Asian IgAN patients with different BMI were grouped together to clarify the relationship between BMI and IgAN progression in Asian populations, so as to provide more ideas and treatment means for the prevention and treatment of IgAN in the future.


Effect of breastfeeding promotion interventions on child growth: a systematic review and meta-analysis.
To update a previous systematic review and meta-analyses about the effect of breastfeeding promotion interventions on child growth. Studies evaluating the effect of any type of breastfeeding promotion intervention on child weight, length (or height) and weight/height (or BMI) were screened. Papers published between 2006 and 2014 were checked using the following databases: PubMed/MEDLINE, Embase, Cochrane Database of Systematic Reviews, Lilacs and SciELO. Sixteen studies were added to 19 other studies identified in the previous review, resulting in 35 studies. Meta-analyses of studies reporting on mean weight, length, weight/length or BMI showed that the interventions had no impact on weight or length/height z scores [pooled effect: 0.03 (95% confidence interval: -0.06;0.12) and 0.03 (95% confidence interval: -0.02;0.08), respectively] and had a modest, but significant, reduction in body mass index/weight-for-height z scores [z score mean difference: -0.06 (95% confidence interval: -0.12;0.00)], which was limited to studies from low- and high-incomes settings. For all three outcomes, there was important heterogeneity among studies, which should be taken into account when interpreting the results. Breastfeeding promotion interventions were not associated with significant changes in weight or length, but led to a modest, albeit significant, reduction in body mass index/weight-for-height z scores.


Microbial interactions and dynamic changes of volatile flavor compounds during the fermentation of traditional kombucha.
This study aims to explore the core microbiota of kombucha and to discover potential correlations between microbiota and volatile flavor compounds. The total acidity and microbial colony numbers changed dramatically in different fermentation periods of kombucha. Microbial analysis based on high throughput sequencing technology showed that the bacteria of Komagataeibacter, Pseudomonas, Burkholderia, Ralstonia, Halomonas, Sphingomonas and fungi of Dekkera, Saccharomyces cerevisiae, Botryotrichum, Monascus, Pichia were the dominant genera. In addition, the correlation coefficients between the bacteria and fungi were different. The volatile flavor compounds of alcohols, acids, esters, aldehydes, ketones, phenolics, and terpenes were identified using headspace solid-phase microextraction combined with gas chromatography coupled with mass spectrometry. Typically, the concentrations of ethanol, acetic acid, and ethyl acetate was 71.59-248.23 μg/L, 97.73-849.00 μg/L, and 44.52-181.59 μg/L, respectively, during fermentation. This study is helpful to understand the dynamic changes of microbial communities and volatile flavor compounds during the fermentation of kombucha.


Ingestion without inactivation of bacteriophages by Tetrahymena.
Tetrahymena has been shown to ingest and inactivate bacteriophages, such as T4, in co-incubation experiments. In this study, Tetrahymena thermophila failed to inactivate phages PhiX174 and MS2 in co-incubations, although PhiX174 were ingested by T. thermophila, as demonstrated by: (1) recovery at defecation in a pulse-chase experiment, (2) recovery from Tetrahymena by detergent lysis, and (3) transmission electron microscopy. We conclude, therefore, that the phages must be digestion-resistant. Internalized PhiX174 were further shown to be partially protected from lethal damage by ultraviolet (UV) C and UVB irradiation. Finally, ingested PhiX174 were shown to be rapidly transported through buffer in a horizontal swimming, race tube-like assay. The transport and protection of phages may confer evolutionary advantages that explain the acquisition of digestion-resistance by some phages.


[Efficacy of HSV-tk/GCV system on human laryngeal squamous cell cancer in vitro].
Efficacy of HSV-tk/GCV system antitumor effects was assessed on human laryngeal cancer cell line Hep-2 in vitro. To assess the HSV-tk/CGV system whether has an antitumour effect on human laryngeal squamous cell cancer Hep-2 in vitro. The mechanisms of cytotoxity were also assessed. Hep-2 cells were transfected with HSV-tk gene by lipofection. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the HSV-tk gene expression. MTT was utilized to test for the cytotoxicity of this system. The cell-circle arrest and apoptosis were analyzed by flowcytometry assay. HSV-tk gene transfected cells demonstrated obvious cytoreductivity followed by ganciclovir (GCV) administration and this cytoreductivity showed partial GCV dose-independent. HSV-tk gene transfected cells demonstrated obvious s-phase arrest, no apoptosis and necrosis occurred. The HSV-tk/GCV system can inhabit the growth of Hep-2 cells effectively. S-phase arrest perhaps is the main reason that leads to the cell inhibition in our study. HSV-tk/GCV system has potential antitumor effects for the future clinical practice.


[The method of examination and clinical application of magnetic nuclear resonance in the diagnosis of facial skeleton].
On the basis of modern literature the present state of knowledge on MNR and the diagnostic effectiveness of this method in various diseases of the facial skeleton are discussed. The diagnostic effectiveness of MNR is compared to that of computed tomography.


Tuning the cell fate of neurons and glia by microRNAs.
The proper function of the nervous system depends on precise production and connection of distinct neurons and glia. Cell fate determination of neurons and glia is tightly controlled by complex gene expression regulation in the developing and adult nervous system. Emerging evidence has demonstrated the importance of noncoding microRNAs (miRNAs) in neural development and function. This review highlights current discoveries of miRNA functions in specifying neuronal and glial cell fate. We summarize the roles of miRNAs in expansion and differentiation of neural stem cells, specification of neuronal subtypes and glial cells, reprogramming of functional neurons from embryonic stem cells and fibroblasts, and left-right asymmetric organization of neuronal subtypes. Investigating the network of interactions between miRNAs and target genes will reveal new gene regulation machinery involved in tuning the cell fate decisions of neurons and glia.


Targeting reactive oxygen species, reactive nitrogen species and inflammation in MPTP neurotoxicity and Parkinson's disease.
Parkinson's disease (PD) is the second most frequent neurodegenerative disorder after Alzheimer's disease. The main clinical features of PD include tremor, bradykinesia, rigidity and postural instability. The primary pathology of PD is degeneration of dopaminergic neurons in the substantia nigra pars compacta, resulting in loss of the nigrostriatal pathway and a reduction of dopamine contents in the striatum. The biochemical and cellular changes that occur following the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are remarkably similar to that seen in idiopathic PD. Recent evidence shows that oxidative stress contributes to the cascade leading to dopaminergic cell degeneration in PD. However, oxidative stress is intimately linked to other components of neurodegenerative process, such as nitric oxide stress and inflammation. Recently, there is convincing evidence for the involvement of nitric oxide that reacts with superoxide to produce peroxynitrite and ultimately hydroxyl radical production. In view of these new insights, however, the role of reactive nitrogen species, reactive oxygen species and inflammation against MPTP neurotoxicity is not fully understood. In this review, we discuss the possible role of reactive nitrogen species, reactive oxygen species and inflammation in the dopaminergic neurons against MPTP neurotoxicity.


Cluster of macrolide-resistant Mycoplasma pneumoniae infections in Illinois in 2012.
Macrolide-resistant Mycoplasma pneumoniae is an increasing problem worldwide but is not well documented in the United States. We report a cluster of macrolide-resistant M. pneumoniae cases among a mother and two daughters.


Incorporation of phosphotyrosyl mimetic 4-(phosphonodifluoromethyl)phenylalanine (F2Pmp) into signal transduction-directed peptides.
Phosphotyrosyl (pTyr)-containing sequences in proteins serve important roles in cellular signal transduction. Often, synthetic pTyr-containing peptides based on cognate sequences surrounding these pTyr residues can exhibit pharmacologically useful properties of full phosphoproteins. However, such pTyr-containing peptides have limited use in whole-cell systems resulting from lability of the phosphate ester bond to protein-tyrosine phosphatases (PTPs). For this reason, a number of phosphatase-stable pTyr mimetics have been developed that retain certain of the chemical and pharmacological properties of pTyr itself. Among these, difluoro-phosphonomethyl phenylalanine (F2Pmp) has shown widespread utility in a variety of signal transduction settings, particularly those involving PTPs. This chapter provides practical techniques for the synthesis of a range of F2Pmp-containing peptides.


Hypoglycemia increases serum interleukin-6 levels in healthy men and women.
Inflammation may have a major role in the pathogenesis and prognosis of critical illness. Hyperglycemia increases levels of the inflammatory cytokine interleukin-6 (IL-6) and is associated with increased risks of morbidity and mortality. Because hypoglycemia is also associated with adverse outcomes, we tested the hypothesis that hypoglycemia increases IL-6. Seventeen healthy men and women participated in hypoglycemic and euglycemic-hyperinsulinemic clamp studies (target blood glucose levels 2.7 and 5.0 mmol/l, respectively), separated by 1-3 months. IL-6, ACTH, and cortisol were measured at baseline and at 45, 75, 105, and 135 min after initiation of the insulin infusion. IL-6, ACTH, and cortisol levels increased significantly (P < 0.0001) during hypoglycemia but not euglycemia. IL-6 increased from mean +/- SEM 1.0 +/- 0.2 pg/ml at baseline to 2.6 +/- 0.2 pg/ml after 135 min of hypoglycemia, whereas IL-6 levels were unchanged during euglycemia. Hypoglycemia increases IL-6 levels in healthy individuals.


The use of ozone in the remediation of polycyclic aromatic hydrocarbon contaminated soil.
The potential of using ozone for the removal of phenanthrene from several different soils, both alone and in combination with biodegradation using a microbial inoculant (Pseudomonas alcaligenes PA-10), was examined. The greater the water content of the soil the less effective the ozone treatment, with air-dried soils showing the greatest removal of phenanthrene; while soils with higher levels of clay also reduced the effectiveness of the ozone treatments. However, at least a 50% reduction in phenanthrene levels was achieved in air-dried soil after an ozone treatment of 6 h at 20 ppm, with up to 85% removal of phenanthrene achieved in sandy soils. The biodegradation results indicate that P. alcaligenes PA-10 may be useful as an inoculant for the removal of PAHs from contaminated soils. Under the conditions used in our experiments, however, pre-ozonation did not enhance subsequent biodegradation of phenanthrene in the soils. Similar levels of phenanthrene removal occurred in both non-ozonated and ozonated Cruden Bay soil inoculated with P. alcaligenes PA-10. However, the biodegradation of phenanthrene in ozonated Boyndie soil was much slower. This may be due to the release of toxic products in this soil during ozonation.


Amyotrophic lateral sclerosis/motor neuron disease deaths in the United States, 1999-2009.
Our objective was to examine trends and epidemiology of amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) associated deaths in the United States. ALS/MND associated death rates and trends in the United States for 1999-2009 were examined using the multiple cause-of-death mortality data. Age-specific and age-adjusted death rates were calculated. For 1999-2009, the average annual age-adjusted death rate was 2.17/100,000 persons. The age-specific rate increased with age until 75-79 years. Males experienced a higher death rate than females. There was no definitive trend in the annual ALS/MND associated death rate, although analyses suggested a possible decrease (p = 0.05); however, the rate increased for persons 20-49 years of age and declined for persons ≥ 65 years of age. The annual rate for males decreased whereas the rate for females showed no change. In conclusion, the suggested decreasing annual ALS/MND associated death rate for 1999-2009 contrasts with earlier reports indicating that the incidence and death rate of ALS were increasing. While the ALS/MND associated death rate slightly increased among adults 20-49 years of age, rates declined among two subpopulations at higher risk for ALS/MND--males and persons ≥ 65 years of age. Continued monitoring of ALS/MND mortality data and additional epidemiological studies will be important to further elucidate these epidemiological trends.


[Pleural mesothelioma--problems in diagnosis and clinical course in 25 patients].
Patients with benign pleurafibromas should undergo surgery as suspect thoracic tumors have the potential to become malignant. In benign cases diagnosis can easily be made during the operation. In such a case the prognosis is good and it is seldom necessary to undergo repeated surgery due to recurrence. In the case of malignant pleuramesothelioma the preoperative diagnosis with an exact staging of the tumor is very important to determine an adequate therapeutic regimen. X-ray, CT-scanning, tapping of the pleura fluid and biopsy of the pleura are together insufficient to diagnose a pleuramesothelioma correctly. Since it is not always possible to diagnose a malignant pleuramesothelioma even at thoracoscopy, one should not hesitate to perform an open lung biopsy in order to obtain enough material under adequate vision.


HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis.
High-density lipoprotein (HDL) has been identified as a potential target in the treatment of atherosclerotic vascular disease. The failure of torcetrapib, an inhibitor of cholesteryl ester transfer protein (CETP) that markedly increased HDL levels in a clinical trial, has called into doubt the efficacy of HDL elevation. Recent analysis suggests that failure may have been caused by off-target toxicity and that HDL is functional and promotes regression of atherosclerosis. New studies highlight the central importance of the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 in reducing macrophage foam cell formation, inflammation, and atherosclerosis. A variety of approaches to increasing HDL may eventually be successful in treating atherosclerosis.


The effect of wet-wrap dressing on epidermal barrier in patients with atopic dermatitis.
Wet-wrap dressing has been shown to be effective for atopic dermatitis; however, the therapeutic mechanism of wet-wrap dressing is only the hypothesis based on the recovery of decreased epidermal barrier function. To examine the therapeutic efficacy as well as the mechanism of wet-wrap dressing in atopic dermatitis patients. To examine the difference of non-lesional and lesional atopic skin and to evaluate the change between epidermal barrier function before and after the treatment, SCORAD, epidermal water content, transepidermal water loss, the lipid amount of skin surface, immunohistochemical staining of filaggrin and loricrin, transmission electron microscopic examination, and calcium ion capture cytochemistry method were done in 10 severe form atopic dermatitis patients. In atopic dermatitis patients, SCORAD was clearly decreased, epidermal water content was increased, and transepidermal water loss was decreased after wet-wrap dressing. After wet-wrap dressing, increased release of lamellar body and the recovery of the damaged lamellar structure of intercellular lipid were observed; nevertheless, neither the change in keratinocyte differentiation nor the change of calcium ion gradient was detected. A week after the termination of wet-wrap dressing, increased water content and decreased transepidermal water loss were still maintained. We confirmed the abnormality of the epidermal barrier in atopic dermatitis, and the effects of wet-wrap were associated with the recovery of epidermal barrier. In atopic lesions, wet-wrap dressing induced clinical improvement by the release of lamellar body and the restoration of intercellular lipid lamellar structure.


Opportunity and marginal abatement cost savings from China's pilot carbon emissions permit trading system: Simulating evidence from the industrial sectors.
China has launched pilot carbon emissions permit trading schemes (ETS) in seven regions since 2013/2014 and has established a nationwide ETS in the power industry by the end of 2017. Recent literature has evaluated China's seven pilot regions on design aspects of the ETS, and yet little is known about the potential recovery of economic output loss through introducing the ETS. This study considers the recovery of industrial value added loss and thus measures the abatement cost savings from trading to evaluate the necessity and feasibility of China's pilot ETSs. The analysis develops a parametric and nonparametric combined technique to calculate the opportunity abatement cost savings (i.e., potential abatement cost savings and unrealized abatement cost savings) and marginal abatement cost savings (i.e., changes on carbon shadow prices) in China's pilot ETSs during 2011-2015. It additionally provides an estimation of potential carbon emissions reduction from ETS. Both cross-industrial trading and intertemporal trading are considered, and three simulations, defined as no trading, cross-industrial trading, and cross-industrial and intertemporal trading, are conducted. We found that, i) 1-16% potential abatement cost savings and 2-12% unrealized abatement cost savings would be identified in China's pilot ETS regions. ii) 0.5-33% and 1.6-25% carbon emissions reduction potential would be realized respectively by introducing ETS and eliminating the operational inefficiency of the ETS. iii) Marginal abatement cost savings would both exist in almost all regions if the ETS were implemented and if the ETS were fully operational.


Age‑related brainstem degeneration through microRNA modulation in mice.
Histopathological changes occur in the brainstem during the early stages of Alzheimer's disease (AD), with the pathological changes of the brain lesions ascending progressively in accordance with the Braak staging system. The senescence‑accelerated mouse prone 8 (SAMP8) mouse model has been previously used as a model of age‑dependent neurodegenerative diseases, including AD. In the present study, microRNAs (miRNAs) that were upregulated or downregulated in SAMP8 brainstems were identified using miRNA profiling of samples obtained from miRNA arrays. The preliminary stage of cognitive dysfunction was examined using male 5‑month‑old SAMP8 mice, with age‑matched senescence‑accelerated mouse resistant 1 mice as controls. A Y‑maze alternation test was performed to assess short‑term working memory and miRNA profiling was performed in each region of the dissected brain (brainstem, hippocampus and cerebral cortex). SAMP8 mice tended to be hyperactive, but short‑term working memory was preserved. Two miRNAs were upregulated (miR‑491‑5p and miR‑764‑5p) and two were downregulated (miR‑30e‑3p and miR‑323‑3p) in SAMP8 brainstems. In SAMP8 mice, the expression level of upregulated miRNAs were the highest in the brainstem, wherein age‑related brain degeneration occurs early. It was demonstrated that the order of specific miRNA expression levels corresponded to the progression order of age‑related brain degeneration. Differentially expressed miRNAs regulate multiple processes, including neuronal cell death and neuron formation. Changes in miRNA expression may result in the induction of target proteins during the early stages of neurodegeneration in the brainstem. These findings suggest that studying altered miRNA expression may provide molecular evidence for early age‑related neuropathological changes.


How Do You Fix Diversity Within Orthopaedic Surgery? Change One's "Matter World".
How do you fix diversity within orthopaedic surgery? Start with self. The solutions to diversity problems are not inherently elusive. I would submit that we are failing in the diversity arena because we have yet to agree on a definition and we resultingly have even less of a consensus on a potential solution. We as a profession should recognize that solutions are not societal. They are individual. Moreover, the obstacles that we face in overcoming our diversity ailments are not societal. They too are individual. Before we can set upon solving our collective problems, we must speak to individuals.


Association between prognostic factors and the outcomes of patients infected with SARS-CoV-2 harboring multiple spike protein mutations.
The outcome of SARS-CoV-2 infection is determined by multiple factors, including the viral, host genetics, age, and comorbidities. This study investigated the association between prognostic factors and disease outcomes of patients infected by SARS-CoV-2 with multiple S protein mutations. Fifty-one COVID-19 patients were recruited in this study. Whole-genome sequencing of 170 full-genomes of SARS-CoV-2 was conducted with the Illumina MiSeq sequencer. Most patients (47%) had mild symptoms of COVID-19 followed by moderate (19.6%), no symptoms (13.7%), severe (4%), and critical (2%). Mortality was found in 13.7% of the COVID-19 patients. There was a significant difference between the age of hospitalized patients (53.4 ± 18 years) and the age of non-hospitalized patients (34.6 ± 19) (p = 0.001). The patients' hospitalization was strongly associated with hypertension, diabetes, and anticoagulant and were strongly significant with the OR of 17 (95% CI 2-144; p = 0.001), 4.47 (95% CI 1.07-18.58; p = 0.039), and 27.97 (95% CI 1.54-507.13; p = 0.02), respectively; while the patients' mortality was significantly correlated with patients' age, anticoagulant, steroid, and diabetes, with OR of 8.44 (95% CI 1.5-47.49; p = 0.016), 46.8 (95% CI 4.63-472.77; p = 0.001), 15.75 (95% CI 2-123.86; p = 0.009), and 8.5 (95% CI 1.43-50.66; p = 0.019), respectively. This study found the clade: L (2%), GH (84.3%), GR (11.7%), and O (2%). Besides the D614G mutation, we found L5F (18.8%), V213A (18.8%), and S689R (8.3%). No significant association between multiple S protein mutations and the patients' hospitalization or mortality. Multivariate analysis revealed that hypertension and anticoagulant were the significant factors influencing the hospitalization and mortality of patients with COVID-19 with an OR of 17.06 (95% CI 2.02-144.36; p = 0.009) and 46.8 (95% CI 4.63-472.77; p = 0.001), respectively. Moreover, the multiple S protein mutations almost reached a strong association with patients' hospitalization (p = 0.07). We concluded that hypertension and anticoagulant therapy have a significant impact on COVID-19 outcomes. This study also suggests that multiple S protein mutations may impact the COVID-19 outcomes. This further emphasized the significance of monitoring SARS-CoV-2 variants through genomic surveillance, particularly those that may impact the COVID-19 outcomes.


Temperature response to morphine in paralyzed cats.
Cats, sedated and paralyzed, showed a significant increase in body temperature after intravenous injection of morphine while animals with additional spinal blockade (C3) from injection of 2% lidocaine solution, did not. The results suggest that motor activity is not necessary for morphine-induced hyperthermia in the cat, as had been suggested in the literature.


Pyrrolidinyl phenylurea derivatives as novel CCR3 antagonists.
Optimization starting with our lead compound 1 (IC(50)=4.9 nM) led to the identification of pyrrolidinyl phenylurea derivatives. Further modification toward improvement of the bioavailability provided (R)-1-(1-((6-fluoronaphthalen-2-yl)methyl)pyrrolidin-3-yl)-3-(2-(2-hydroxyethoxy)phenyl)urea 32 (IC(50)=1.7 nM), a potent and orally active CCR3 antagonist.


Isolation, characterization and PCR multiplexing of microsatellite loci for two sub-species of terrestrial isopod Porcellio dilatatus (Crustacea, Oniscidea).
Several microsatellite markers have already been developed for different terrestrial isopod species such as Armadillidium vulgare, A. nasatum and Porcellionides pruinosus. In all these species, the endosymbiont Wolbachia has a feminizing effect that generates a female bias in sex ratio and reduces the number of reproductive males. Thus this can potentially decrease the genetic diversity of host populations. However, in some other isopod species, Wolbachia induces cytoplasmic incompatibility (CI); the most commonly described effect of Wolbachia in arthropods. The CI by rendering some crossings incompatible can reduce the gene flow and strengthen genetic differentiation between isopod populations. To date, the influence of Wolbachia inducing CI on population structure of terrestrial isopods has never been investigated. In this study, we developed 10 polymorphic microsatellite markers shared by two sub-species of Porcellio dilatatus. Crossings between the two sub-species are partially incompatible due to two CI-inducing Wolbachia strains. These new microsatellite markers will allow us to investigate the effect of CI on host genetic differentiation in this species complex.


Cardiogenic shock complicating myocardial infarction.
Cardiogenic shock is the primary cause of death among patients hospitalized with acute myocardial infarction. It is defined as tissue hypoperfusion resulting from ventricular pump failure in the presence of adequate intravascular volume. These patients need rapid assessment and appropriate institution of supportive therapies including vasopressor and inotropic agents, ventilatory support, and intra-aortic balloon pump counterpulsation. Emergency coronary artery revascularization is the only therapy that reduces mortality, and this should be provided early to patients to achieve maximal benefit, unless further care is deemed futile. Whereas newer support devices can provide better hemodynamic augmentation, their impact on mortality is limited. Novel therapies are needed to further decrease mortality rates, which remain high despite reperfusion therapy.


Real-time volumetric imaging of human heart without electrocardiographic gating by 256-detector row computed tomography: initial experience.
The feasibility of human cardiac imaging using a prototype 256-detector row cone-beam computed tomography (256CBCT) scanner without electrocardiographic gating was examined. Two healthy male volunteers were examined by contrast-enhanced 256CBCT. The number of detectors was 912 x 256, each measuring approximately 0.5 mm x 0.5 mm at the center of rotation. The craniocaudal coverage was approximately 100 mm after reconstruction by the Feldkamp-Davis-Kress algorithm. The effective time resolution was 500 milliseconds using a half-scan algorithm. Serial enhancement of the left ventricular myocardium was detected. The right and left coronary arteries at proximal and distal segments were depicted without significant blurring. Although the left ventricular wall motion on cine images was not smooth over time, it was possible to measure ventricular volume and ejection fraction. Using the 256CBCT, it was possible to visualize the coronary arteries, myocardial perfusion, and ventricular contraction simultaneously during a single acquisition.


PTH Assays: Understanding What We Have and Forecasting What We Will Have.
Parathyroid hormone (PTH) assays have evolved continuously for the last 50 years. Since the first radioimmunoassay was described in 1963, several assays based on immunological identification have been published (first generation assays). The routine assays used nowadays are immunometric "sandwich-type". They are based on two different monoclonal antibodies, one amino-terminal and the other carboxyl terminal specific. These second generation assays are widely available and adapted to most of the automation platforms. The specificity of the amino terminal antibody defines if the immunometric assay measures only the bioactive PTH circulating form (including the first amino terminal amino acids) or the "intact" PTH, which includes, besides bioactive PTH, other "long" carboxyl-terminal forms, for example, 7-84-PTH. Assays for "intact" PTH are the most commonly available and the potential advantage of the bioactive PTH assays is still debatable. Next generation of assays will be based on different principles, mainly mass spectrometry in samples submitted to a prior purification and fragmentation steps. These assays will provide information about the whole spectra of PTH peptides in circulation, with a significant increase of the information regarding this biologically important peptide hormone.


Separation of time-based and trial-based accounts of the partial reinforcement extinction effect.
Two appetitive conditioning experiments with rats examined time-based and trial-based accounts of the partial reinforcement extinction effect (PREE). In the PREE, the loss of responding that occurs in extinction is slower when the conditioned stimulus (CS) has been paired with a reinforcer on some of its presentations (partially reinforced) instead of every presentation (continuously reinforced). According to a time-based or "time-accumulation" view (e.g., Gallistel and Gibbon, 2000), the PREE occurs because the organism has learned in partial reinforcement to expect the reinforcer after a larger amount of time has accumulated in the CS over trials. In contrast, according to a trial-based view (e.g., Capaldi, 1967), the PREE occurs because the organism has learned in partial reinforcement to expect the reinforcer after a larger number of CS presentations. Experiment 1 used a procedure that equated partially and continuously reinforced groups on their expected times to reinforcement during conditioning. A PREE was still observed. Experiment 2 then used an extinction procedure that allowed time in the CS and the number of trials to accumulate differentially through extinction. The PREE was still evident when responding was examined as a function of expected time units to the reinforcer, but was eliminated when responding was examined as a function of expected trial units to the reinforcer. There was no evidence that the animal responded according to the ratio of time accumulated during the CS in extinction over the time in the CS expected before the reinforcer. The results thus favor a trial-based account over a time-based account of extinction and the PREE. This article is part of a Special Issue entitled: Associative and Temporal Learning.


A VOLTAMMETRIC FLAVIN MICROELECTRODE FOR USE IN BIOFILMS.
Biofilms used in bioelectrochemical systems are expected to transfer electrons using electron transfer mediators. One mediator type, flavins, which includes flavin mononucleotide, riboflavin, and flavin adenine dinucleotide, has been found to be endogenously produced by Shewanella oneidensis MR-1. However, the presence and concentration of flavins inside a S. oneidensis MR-1 biofilm have never been reported. The goal of this study was to develop a flavin microelectrode capable of measuring flavins inside a living biofilm and apply it to a biofilm which produces flavins. Because flavins are electrochemically active molecules, the flavin microelectrode was based on detection via square-wave voltammetry. The microelectrode consisted of a carbon working electrode with a 10-30 μm tip diameter, a built-in platinum counter electrode, and a Ag/AgCl reference electrode, all enclosed in a glass outer case. The microelectrode was calibrated between 0.1 μM and 10 μM flavins and showed a linear correlation between flavin concentration and peak currents located at -424 mV(Ag/AgCl) on a square-wave voltammogram. We also developed a model to explain the electrochemical mechanism of flavin detection, and to determine the effective surface area of the microelectrode, the standard reduction potential, and the transfer coefficient. We found that the effective surface area of the microelectrode was close to 100 times the projected surface area. The model predicted a standard reduction potential for RF/RFH2 of -419 mV(Ag/AgCl) at 20 °C and a transfer coefficient of 0.45. Lastly, we measured flavin concentration inside a S. oneidensis MR-1 biofilm grown on a glass surface using oxygen as the electron acceptor. The flavin concentration reached 0.7 μM, increasing near the bottom of the biofilm, where no oxygen was present. This shows the possibility that flavins are produced in the anaerobic zone to act as intermediate electron acceptors in the deeper parts of the biofilm, where there is no oxygen.